A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients With Duchenne Muscular Dystrophy
Phase: PHASE3
Conditions: Muscular Dystrophy, Duchenne
Sponsor: Catabasis Pharmaceuticals

 
 
 
    
 
 
 
 
 
 
Official Title: A Randomized, Double-Blind, Placebo controlled, Global Phase 3 Study of Edasalonexent 
in Pediatric Patients with Duchenne Muscular Dystrophy 
 
NCT Number: NCT03703882 
 
Applicant/MAH: Catabasis Pharmaceuticals Inc. 
 
Version Date: 16 April 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
2 
 
 
 
 
Investigator’s Agreement 
 
This protocol was designed and will be conducted, recorded, and reported in accordance with the Protocol and 
in compliance with the principles of Good Clinical Practice (GCP), and any other applicable regulatory 
requirements.  GCP principles are stated in “Guidance for Good Clinical Practice,” International Council for 
Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. 
I have read and agree to abide by the requirements of this protocol. 
 
 
Principal Investigator Signature 
Date 
 
 
 
 
Principal Investigator Name (please print or type) 
 
 
 

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Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
5 
1. 
SYNOPSIS 
Name of Sponsor/Company: 
Catabasis Pharmaceuticals, Inc. 
Name of Investigational Product: 
Edasalonexent 
Name of Active Ingredient: 
Edasalonexent 
Title of Study:  
A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric 
Patients with Duchenne Muscular Dystrophy 
Phase of Development: 3 
Objectives:  
Primary 
• 
To assess the efficacy of edasalonexent as measured by change from Baseline (CFB) on North Star 
Ambulatory Assessment (NSAA) Total Score in pediatric patients with Duchenne muscular 
dystrophy (DMD)  
Secondary  
• 
To assess the safety and tolerability of edasalonexent in pediatric patients with DMD  
• 
To assess the effects of edasalonexent on physical function as measured by the 10-meter walk/run 
test (10MWT), time to stand from supine, and the 4-stair climb in pediatric patients with DMD  
Methodology:  
This is a randomized, double-blind, placebo-controlled, Phase 3, multisite study of edasalonexent in pediatric 
patients with DMD.  Approximately 126 patients will be enrolled.   
Eligible patients will be ambulatory boys from ≥4.0 to <8.0 years of age with a confirmed diagnosis of DMD 
who have not used steroids within 24 weeks prior to treatment initiation (Day 1).   
As shown in the figure below, the study includes a 52-week, double-blind, placebo-controlled period 
comparing 1 dose level of edasalonexent with placebo, followed by a 2-week follow-up.  
Following completion of the treatment period and Primary Endpoint evaluation, patients may elect to 
continue in the open-label extension study, pending approval by appropriate ethics committees and regulatory 
authorities.  Patients who choose not to participate should complete the safety follow-up within 2 weeks. 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
6 
CAT-1004-301 – Overview of Study Design 
 
Double-Blind Placebo-Controlled Study 
Following a Screening period to determine eligibility, approximately 126 patients will be randomized 2:1 to 
receive edasalonexent 100 mg/kg/day (administered as approximately 33 mg/kg 3 times per day [TID]) or 
placebo in double-blind fashion daily for 52 weeks.  Randomization will be stratified by Baseline age 
(≤6.0 years or >6.0 years), time to stand from supine (≤5 seconds or >5 seconds), treatment with eteplirsen 
(yes or no), and region (North America or Europe/Asia/Australia).  If siblings are enrolled, they will be 
assigned to the same treatment group. 
Screening procedures should be performed within 4 weeks prior to the start of treatment on Day 1.  At the 
discretion of the Investigator, informed consent, collection of medical history and demographic data, and 
collection of laboratory Screening assessments may be completed remotely by a qualified medical 
professional at an alternative site setting.   
After Screening, eligible patients will complete Baseline procedures and begin receiving study drug 
(edasalonexent or placebo) on Day 1.  Study drug will be orally administered as soft-gel capsules in divided 
doses taken with food containing at least 8 grams of fat.  Patients and their families will be provided with 
written and verbal instructions for study drug administration, and subsequent doses will be administered 
remotely, except for on scheduled site visits as specified in the Schedule of Assessments (SOA).   
Patients will have site visits approximately every 13 weeks with site calls in between as specified in the SOA.  
The efficacy and safety of edasalonexent will be assessed at the timepoints specified in the SOA.   
Efficacy assessments will include:  the NSAA; timed function tests (TFTs) including the 10MWT, time to 
stand from supine, and the 4-stair climb; muscle strength testing; Performance of Upper Limb (PUL) entry 
item assessment; and assessment of health-related physical functioning as measured by the PODCI. 
Safety assessments will include collection of adverse events (AEs), serious adverse events (SAEs), growth 
parameters, vital signs, physical examinations, clinical laboratory testing (including chemistry, hematology, 
and urinalysis), assessment of adrenal function (adrenocorticotrophic hormone [ACTH] and cortisol levels), 
and electrocardiogram (ECG).   
For analysis of pharmacokinetics (PK), blood samples will be obtained for determination of edasalonexent 
and its metabolite concentrations.   
Additionally, blood samples will be drawn to evaluate gene expression, micro-RNA, and protein biomarkers 
that might predict the course of disease and/or responses to treatment. 
Additional cardiac ECG monitoring will be performed via a wearable cardiac monitoring device if approved 
for use in the participating country.  

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
7 
Lateral thoracolumbar spine radiography and dual energy X-ray absorptiometry (DXA) scan will be 
performed if approved by the appropriate governing bodies at each site or country. 
A safety follow-up should occur within 2 weeks of the last dose of study drug for collection of AEs.   
Inclusion / Exclusion Criteria:  
The eligibility criteria are designed to include only patients with an established diagnosis of DMD based on 
clinical, laboratory and genetic findings who are sufficiently well (both in terms of DMD and in terms of 
concomitant illness) to safely participate in study procedures and provide interpretable results.  
Inclusion Criteria 
A patient must meet all the following criteria to be eligible for this study. 
1. Written consent/assent by patient and/or legal guardian as per regional and/or Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) requirements  
2. Diagnosis of DMD based on a clinical phenotype with increased serum creatine kinase (CK) and 
documentation of mutation(s) in the dystrophin gene known to be associated with a DMD phenotype  
3. Male sex by birth 
4. Age ≥4.0 to <8.0 years (at the time of consent) 
5. Able to perform stand from supine without assistance in ≤ 10 seconds  
6. Able to perform the 10MWT and 4-stair climb 
7. Able to swallow placebo capsules at the Screening Visit 
8. Followed by a doctor or medical professional who coordinates Duchenne care on a regular basis and 
willingness to disclose patient's study participation with medical professionals 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study. 
1. Use of corticosteroids within 24 weeks prior to Day 1; use of inhaled, intranasal, and topical 
corticosteroids is permitted 
2. Use of an investigational drug, idebenone, or dystrophin-focused therapy within 4 weeks or a period 
of 5 half-lives duration prior to Day 1 (whichever is longer) or ongoing participation in any other 
therapeutic clinical trial.  Exception: Patients who have received at least 24 weeks of a stable dose of 
eteplirsen prior to Day 1, and expected to continue treatment, will be eligible.  
3. Use of the following within 4 weeks prior to Day 1: immunosuppressive therapy, warfarin, 
phenytoin, S-mephenytoin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, alfentanil, 
pimozide, quinidine, sirolimus, tacrolimus, or paclitaxel 
4. Use of human growth hormone within 3 months prior to Day 1 
5. Documented positive hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency 
virus (HIV) or a known risk factor for hepatitis such as a blood transfusion within 12 weeks prior to 
Day 1 
6. Hemoglobin <10.5 g/dL 
7. Abnormal gamma-glutamyl transferase (GGT) (>laboratory’s upper limit of normal [ULN]) 
8. Other prior or ongoing medical condition, known hypersensitivity to omega-3 fatty acids, physical 
findings, ECG findings, or laboratory abnormality (including but not limited to renal insufficiency or 
impaired hepatic function) that, in the Investigator’s opinion, could adversely affect the safety of the 
patient, make it unlikely that the course of treatment or follow-up would be completed, or impair the 
assessment of study results (e.g., a gastrointestinal condition that would impair fat absorption) 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
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9. In the Investigator’s opinion, unwilling or unable for any reason (e.g., attentional or behavioral 
issues) to complete all study assessments and laboratory tests and comply with scheduled visits, 
administration of drug, and all other study procedures 
Note:  Patients may be re-tested or re-screened for eligibility after discussion with the Medical Monitor. 
Number of Patients:  
Approximately 126 patients will be enrolled in a 2:1 ratio to receive edasalonexent or placebo. 
Investigational Product, Dosage and Mode of Administration:  
Edasalonexent 100 mg/kg/day (administered as approximately 33 mg/kg TID).  The Sponsor will supply 
edasalonexent soft-gel capsules at a dose strength of 250 mg for oral administration; 100-mg capsules will be 
available should patients need a smaller size capsule to facilitate swallowing.  An Interactive Web Response 
System (IWRS) will determine each patient’s weight-based dosing; the total daily dose will be within 80% to 
125% of each target dose.  Study drug will be taken with food containing at least 8 grams of fat.  
Duration of treatment:  
The approximate duration of participation for each patient will be 58 weeks, including the 4-week Screening 
period, the 52-week dosing period, and the 2-week follow-up.   
Reference therapy, dosage and mode of administration:  
The Sponsor will supply placebo capsules for oral administration for assessment of swallowing prior to 
initiation of treatment and for administration during the study.  The appearance and administration of placebo 
will be identical to that of the investigational product. 
Criteria for evaluation: 
Efficacy  
The primary efficacy assessment is the NSAA Total Score. 
Secondary efficacy assessments will include the following:  
• 
10MWT 
• 
Stand from supine 
• 
4-stair climb 
Additional efficacy assessments will include the following: 
• 
Muscle strength testing 
• 
PUL entry item assessment  
• 
PODCI Transfer and Basic Mobility scale 
Safety: 
Safety will be evaluated in terms of all treatment-emergent adverse events (TEAEs) and SAEs, as well as 
physical examination, growth parameters, vital signs, clinical laboratory parameters (including chemistry, 
hematology and urinalysis), adrenal function (ACTH and cortisol levels), and ECG.  Data from ECGs will be 
locally read and centrally evaluated.   
Additional Analyses: 
Plasma and urine PK will be evaluated in terms of concentrations of edasalonexent and its metabolites.   
PD evaluations may include gene expression, micro-RNA, and circulating protein biomarkers to evaluate the 
course of disease and/or responses to treatment. 
In addition, deoxyribonucleic acid (DNA) samples may be collected to permit pharmacogenomics analysis 
of potential markers of clinical risk/benefit as well as drug metabolizing enzyme and/or transporter analysis.  

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
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To measure heart rate and heart rate variability, additional cardiac monitoring will be performed for 
approximately 48 hours via a wearable cardiac monitoring device if approved for use in the participating 
country. 
To measure bone health, lateral thoracolumbar spine radiography and DXA scan will be performed if 
approved by the appropriate governing bodies at each site or country.  Bone radiography will be locally read 
and centrally evaluated. 
Statistical Methods:  
Analysis Populations: 
The Randomized Population consists of all patients who are randomized into the study.  
The Safety Population will consist of all patients who receive at least 1 dose of study drug.  
The Full Analysis Population for efficacy analyses will be a modified intent to treat (mITT) population and 
will consist of all patients in the Randomized Population who receive at least 1 dose of study drug and 
provide at least 1 valid post Baseline NSAA efficacy assessment.   
The Per Protocol (PP) Population will consist of all patients in the Full Analysis Population who complete the 
study, without any significant protocol violations.   
The PK Population will consist of all patients in the Safety Population who receive at least 1 dose of 
edasalonexent and have at least 1 measured plasma concentration.   
Other analysis populations may be defined in the statistical analysis plan (SAP). 
General Considerations: 
Descriptive characteristics for continuous variables will be summarized using mean, median, standard 
deviation, minimum and maximum values.  For categorical variables, the number and percentage of patients 
(or observations) will be reported.   
Unless otherwise defined for a particular endpoint, a patient’s baseline value is the last measurement prior to 
initiation of study drug. 
Demographics, Baseline characteristics, and DMD-specific medical history will be listed by patient, and 
summarized by treatment group.   
Results of efficacy assessments will be listed by patient, and summarized by treatment group and timepoint as 
applicable.  Descriptive statistics will be calculated for efficacy data as well as for CFB and differences 
between groups as applicable.   
Results of safety assessments will be listed by patient, and summarized by treatment group and timepoint as 
applicable.  Descriptive statistics will be calculated for safety assessments by treatment group and timepoint 
as applicable.  AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®) 
dictionary and will be categorized by system organ class and preferred term.  Abnormal clinical laboratory 
values will be identified as outside (above or below) the normal range and will be evaluated for clinically 
notable abnormalities.  Reference (normal) ranges for laboratory parameters will be included in the clinical 
study report.  Shift tables will be implemented as applicable.  Concomitant medications will be listed by 
treatment and coded using the World Health Organization (WHO) Drug dictionary.  Medical history will be 
listed and coded by patient using the MedDRA® dictionary.  
Results of PK and PD assessments will be listed by patient and summarized by treatment group and timepoint 
as applicable. 
Efficacy Endpoints and Analyses: 
The primary efficacy endpoint will be the CFB in the NSAA Total Score at Week 52.  
The CFB in NSAA Total Score will be analyzed using a mixed-model repeated-measures (MMRM) analysis 
of covariance (ANCOVA), implemented using SAS® Proc Mixed.  The factors in the model will be Baseline 
age (≤6.0 years or >6.0 years), time to stand from supine (≤5 seconds or >5 seconds), region (North America 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
10 
or Europe/Asia/Australia), visit, treatment group, Baseline value, Baseline value by visit, and treatment group 
by visit.   
The primary analysis will test the treatment difference at Week 52 via the MMRM model at the 2-sided 0.05 
level. The primary efficacy analysis will be performed on the Full Analysis Population with exclusions that 
may be defined in the SAP, such as excluding patients receiving treatment with eteplirsen. 
Secondary efficacy endpoints will include the CFB on the following:  
• 
10MWT speed 
• 
Stand from supine speed 
• 
4-stair climb speed 
The secondary efficacy endpoints will be analyzed in a similar manner to the primary efficacy endpoint 
analysis.   
Additional efficacy endpoints will include CFB on the following: 
• 
Muscle strength testing  
• 
PUL entry item assessment 
• 
PODCI Transfer and Basic Mobility scale 
Determination of Sample Size 
Approximately 126 patients will be randomized to either edasalonexent or placebo in a 2:1 ratio.  Based on 
Phase 1/2 data of changes in NSAA in this age group, an effect size of 0.625 is assumed.  With this effect 
size, and assuming a dropout rate of approximately 20%, the study has approximately 80% power to show a 
difference between the treatment groups at a 2-sided type I error rate of 0.05.   

Clinical Trial Protocol:  CAT-1004-301 
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TABLE OF CONTENTS 
SPONSOR’S AGREEMENT .......................................................................................................... 3 
PROCEDURES IN CASE OF EMERGENCY ............................................................................... 4 
1. 
SYNOPSIS ................................................................................................................... 5 
TABLE OF CONTENTS .............................................................................................................. 11 
LIST OF TABLES ........................................................................................................................ 15 
LIST OF FIGURES ....................................................................................................................... 15 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................... 16 
2. 
INTRODUCTION ...................................................................................................... 18 
2.1. 
Summary of Edasalonexent Nonclinical Data ........................................................... 19 
2.2. 
Summary of Edasalonexent Clinical Experience ....................................................... 20 
2.3. 
Dose Selection Rationale ........................................................................................... 21 
3. 
TRIAL OBJECTIVES ............................................................................................... 22 
3.1. 
Primary ....................................................................................................................... 22 
3.2. 
Secondary ................................................................................................................... 22 
3.3. 
Overall Study Design ................................................................................................. 22 
3.3.1. 
Double-Blind Placebo-Controlled Study Design ....................................................... 23 
3.3.2. 
Study Conduct during the COVID-19 Pandemic ....................................................... 23 
3.3.3. 
Completion of a Patient’s Participation in the Study and Overall Study 
Completion ................................................................................................................. 24 
3.3.3.1. 
Completion of a Patient’s Participation in the Study ................................................. 24 
3.3.3.2. 
Premature Patient Discontinuation from the Study .................................................... 24 
3.3.3.3. 
Overall Study Completion .......................................................................................... 24 
3.4. 
Discussion of Study Design, Including Choice of Control Group ............................. 24 
4. 
PATIENT POPULATION AND SELECTION ......................................................... 27 
4.1. 
Inclusion Criteria ........................................................................................................ 27 
4.2. 
Exclusion Criteria ....................................................................................................... 27 
5. 
TREATMENTS ......................................................................................................... 29 
5.1. 
Treatments Administered ........................................................................................... 29 
5.1.1. 
Double-Blind Placebo-Controlled Treatment ............................................................ 29 
5.1.2. 
Investigational Product(s) Description ....................................................................... 29 
5.1.3. 
Packaging and Labeling ............................................................................................. 29 
5.1.4. 
Storage ........................................................................................................................ 29 

Clinical Trial Protocol:  CAT-1004-301 
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5.1.5. 
Preparation and Administration ................................................................................. 29 
5.2. 
Dosing Considerations ............................................................................................... 30 
5.2.1. 
Dose Selection Rationale ........................................................................................... 30 
5.2.2. 
Dose Modification or Reduction ................................................................................ 30 
5.2.3. 
Safety Monitoring ...................................................................................................... 30 
5.2.4. 
Treatment Compliance ............................................................................................... 30 
5.2.5. 
Treatment Discontinuation ......................................................................................... 30 
5.3. 
Prior and Concomitant Medications and Therapeutic Procedures ............................. 30 
5.4. 
Method of Assigning Patients to Treatment ............................................................... 31 
5.5. 
Blinding and Randomization ...................................................................................... 31 
5.5.1. 
Blinding and Randomization ...................................................................................... 31 
5.5.2. 
Scheduled Unblinding ................................................................................................ 32 
5.5.3. 
Emergency Unblinding .............................................................................................. 32 
6. 
STUDY ASSESSMENTS .......................................................................................... 33 
6.1. 
Study Schedule of Events ........................................................................................... 33 
6.2. 
Screening and Baseline Assessments and Start of Treatment .................................... 33 
6.3. 
Efficacy Assessments ................................................................................................. 33 
6.3.1. 
North Star Ambulatory Assessment (NSAA) ............................................................ 33 
6.3.2. 
Timed Function Testing ............................................................................................. 34 
6.3.3. 
Muscle Strength Testing ............................................................................................ 34 
6.3.4. 
Performance of Upper Limb (PUL) Scale ................................................................. 34 
6.3.5. 
The Pediatric Outcomes Data Collection Instrument (PODCI) ................................. 35 
6.3.6. 
Assessor Training and Ensuring Compliance with Protocol-Specified Test-
Administration. ........................................................................................................... 35 
6.4. 
Safety Assessments .................................................................................................... 35 
6.4.1. 
Physical Examination and Growth Parameters .......................................................... 36 
6.4.2. 
Vital Signs .................................................................................................................. 36 
6.4.3. 
Clinical Laboratory Tests ........................................................................................... 36 
6.4.4. 
Electrocardiogram ...................................................................................................... 36 
6.4.5. 
Concomitant Medications and Therapies ................................................................... 37 
6.5. 
Pharmacokinetic Assessments ................................................................................... 37 
6.6. 
Pharmacodynamic Assessments ................................................................................. 37 
6.7. 
Cardiac Monitoring .................................................................................................... 37 

Clinical Trial Protocol:  CAT-1004-301 
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6.8. 
Bone Evaluations ....................................................................................................... 38 
6.9. 
Study Drug Acceptability ........................................................................................... 38 
6.10. 
Total Volume of Blood Collected .............................................................................. 38 
7. 
ADVERSE EVENTS AND ADVERSE EVENT REPORTING .............................. 39 
7.1. 
Timeframe for Collection of Adverse Events ............................................................ 39 
7.1.1. 
Adverse Events Occurring Prior to Study Treatment ................................................ 39 
7.1.2. 
Adverse Events Occurring After Study Treatment .................................................... 39 
7.1.3. 
Adverse Events Occurring Following Patient Discontinuation of Treatment ........... 39 
7.2. 
Definitions .................................................................................................................. 39 
7.2.1. 
Definition of an Adverse Event .................................................................................. 39 
7.2.2. 
Definition of a Serious Adverse Event ....................................................................... 40 
7.3. 
Evaluation of Adverse Events/Serious Adverse Events ............................................. 40 
7.3.1. 
Relationship to Study Treatment ................................................................................ 40 
7.3.2. 
Severity Grading of Adverse Event Scoring .............................................................. 40 
7.3.3. 
Outcome ..................................................................................................................... 41 
7.3.4. 
Action Taken Regarding the Investigational Product ................................................ 41 
7.4. 
Recording of Adverse Events/Serious Adverse Events ............................................. 42 
7.5. 
COVID-19 Adverse Events and/or Serious Adverse Events ..................................... 42 
7.6. 
Reporting of Serious Adverse Events ........................................................................ 42 
7.7. 
Follow-up of Adverse Events/Serious Adverse Events ............................................. 43 
7.8. 
Pregnancy Reporting .................................................................................................. 43 
7.9. 
Temporary or Persistent Dose Reductions ................................................................. 43 
7.10. 
Monitoring of Abnormal Laboratory Values ............................................................. 43 
7.11. 
Stopping Rules ........................................................................................................... 44 
7.12. 
Restriction on the Lifestyle of Patients ...................................................................... 44 
8. 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT ......... 45 
8.1. 
Recording of Data ...................................................................................................... 45 
8.2. 
Data Quality Assurance .............................................................................................. 45 
8.3. 
Data Management ...................................................................................................... 45 
8.4. 
Data Safety Monitoring Board ................................................................................... 45 
9. 
STATISTICAL METHODS AND PLANNED ANALYSES ................................... 47 
9.1. 
General Considerations .............................................................................................. 47 
9.2. 
Determination of Sample Size ................................................................................... 47 

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9.3. 
Analysis Sets .............................................................................................................. 47 
9.4. 
Demographics and Baseline Characteristics .............................................................. 48 
9.5. 
Concomitant Medications .......................................................................................... 48 
9.6. 
Medical History .......................................................................................................... 48 
9.7. 
DMD-Specific Medical History ................................................................................. 48 
9.8. 
Patient Disposition ..................................................................................................... 48 
9.9. 
Study Treatment Usage and Compliance ................................................................... 48 
9.10. 
Efficacy Analyses ....................................................................................................... 48 
9.10.1. 
Primary Efficacy Endpoint ......................................................................................... 49 
9.10.2. 
Secondary Efficacy Endpoints ................................................................................... 49 
9.10.3. 
Controlling for Multiplicity ........................................................................................ 49 
9.10.4. 
Sensitivity Analyses of the Primary and Secondary Efficacy Endpoints .................. 49 
9.10.5. 
Additional Efficacy Endpoints ................................................................................... 49 
9.11. 
Pharmacokinetic Analyses ......................................................................................... 50 
9.12. 
Safety Analyses .......................................................................................................... 50 
9.12.1. 
Physical Examination, Growth Parameters, Electrocardiograms, and Vital Signs .... 51 
9.12.2. 
Clinical Laboratory Tests ........................................................................................... 51 
9.12.3. 
Adverse Events ........................................................................................................... 51 
9.13. 
Pharmacodynamic Analyses ...................................................................................... 51 
9.14. 
Cardiac Monitoring .................................................................................................... 52 
9.15. 
Bone Evaluations ....................................................................................................... 52 
9.16. 
Other Statistical Issues ............................................................................................... 52 
9.16.1. 
Missing or Invalid Data .............................................................................................. 52 
9.16.2. 
Multisite Issues ........................................................................................................... 52 
9.16.3. 
Subgroup Analyses ..................................................................................................... 52 
10. 
SPECIAL REQUIREMENTS AND PROCEDURES ............................................... 53 
10.1. 
Institutional and Ethics Review ................................................................................. 53 
10.2. 
Changes to the Conduct of the Study or Protocol ...................................................... 53 
10.3. 
Investigator’s Responsibilities ................................................................................... 53 
10.3.1. 
Patient Informed Consent ........................................................................................... 53 
10.3.2. 
Case Report Forms ..................................................................................................... 53 
10.3.3. 
Record Retention ........................................................................................................ 54 
10.3.4. 
Monitoring .................................................................................................................. 54 

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10.3.5. 
Study or Site Termination .......................................................................................... 54 
10.3.6. 
Investigational Product Control ................................................................................. 55 
10.3.6.1. 
Receipt of Investigational Product ............................................................................. 55 
10.3.6.2. 
Disposition of Unused Investigational Product .......................................................... 55 
10.3.6.3. 
Product Handling and Complaints Reporting ............................................................ 55 
10.3.7. 
Disclosure of Data ...................................................................................................... 55 
10.3.8. 
Confidentiality and Data Privacy ............................................................................... 55 
11. 
REFERENCES ........................................................................................................... 57 
APPENDIX 1. SCHEDULE OF ASSESSMENTS .................................................................... 60 
APPENDIX 2. POTENTIAL MODIFICATIONS TO THE SCHEDULE OF 
ASSESSMENTS DURING THE COVID-19 PANDEMIC ...................................... 62 
APPENDIX 3. LIST OF CLINICAL LABORATORY ASSESSMENTS ................................ 65 
APPENDIX 4. STUDY DRUG QUESTIONNAIRE ................................................................. 66 
APPENDIX 5. PEDIATRIC OUTCOMES QUESTIONNAIRE (PODCI) ............................... 68 
 
LIST OF TABLES 
Table 1: 
Emergency Contact Information .................................................................................. 4 
Table 2: 
Prohibited Prior and Concomitant Medications ......................................................... 31 
 
LIST OF FIGURES 
Figure 1: 
CAT-1004-301 – Overview of Study Design ............................................................ 22 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and terms are used in this study protocol. 
Abbreviation 
Definition 
10MWT  
10-meter walk/run test  
ACTH 
adrenocorticotropic hormone 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
BID 
twice a day 
BMI 
body mass index 
CA 
Competent Authorities 
CFB 
change from Baseline 
Clast 
last quantifiable plasma concentration 
Cmax 
maximum plasma concentration 
CK 
creatine kinase 
DHA 
docosahexaenoic acid 
DMD 
Duchenne muscular dystrophy 
DNA 
deoxyribonucleic acid 
DSMB 
Data Safety Monitoring Board 
DXA 
dual energy X-ray absorptiometry 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
ET 
early termination 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GRMD 
golden retriever muscular dystrophy 
HEENT 
head, eyes, ears, nose, throat 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
LPS 
lipopolysaccharide  

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Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMP9 
matrix metalloproteinase 9 
MMRM 
mixed-model repeated-measures  
MRI 
magnetic resonance imaging 
MuRF1 
muscle RING finger protein 1 
n 
sample size 
NCS 
not clinically significant 
NF-κB 
nuclear factor kappa light chain enhancer of activated B cells  
NOAEL 
no-observed-adverse-effect level 
NSAA 
North Star Ambulatory Assessment  
PD 
pharmacodynamic 
PK 
pharmacokinetic(s) 
PODCI 
Pediatric Outcomes Data Collection Instrument  
PUL 
Performance of Upper Limb 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SDHM 
Study Drug Handling Manual  
SOA 
Schedule of Assessments 
SOC 
System Organ Class 
SOCS3 
suppressor of cytokine signaling 3 
SRM 
Study Reference Manual 
TID 
3 times per day 
TEAE 
treatment emergent adverse event 
TFT 
Timed Function Test 
TNFα 
tumor necrosis factor alpha 
ULN 
upper limit of normal 
WHO 
World Health Organization 
 

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2. 
INTRODUCTION  
The purpose of this multisite, Phase 3 study is to confirm the efficacy and safety of edasalonexent 
(CAT-1004) on ambulatory male pediatric patients with a confirmed diagnosis of Duchenne muscular 
dystrophy (DMD).  The study is a 52-week, double-blind, placebo-controlled study comparing 
100 mg/kg/day of edasalonexent (administered as approximately 33 mg/kg 3 times per day [TID]) 
with placebo.   
Duchenne Muscular Dystrophy 
DMD is a progressively debilitating and ultimately fatal inherited neuromuscular disorder affecting 
approximately 1 in 3,500 to 5,000 live male births worldwide.  It is caused by mutations in the gene 
encoding dystrophin, a critical part of the protein complex that connects the cytoskeletal actin of a 
muscle fiber to the extracellular matrix.  In the absence of dystrophin, the stress of repeated muscle 
contractions damages the sarcolemma resulting in repeated cycles of cellular degeneration, 
progressively failing regeneration, and inflammation (Blake, 2002; Emery, 2002).  Over time, muscle 
is replaced by fibrotic tissue and fat.  Of note, while a lack of dystrophin is the primary cause of 
DMD, it is not sufficient for disease progression, as evidenced by the heterogeneity in disease 
progression among different muscles (Porter, 2003; Hu, 2015). 
Affected children are usually diagnosed between the ages of 3 to 5 years when they begin to show 
lordosis, waddling gait, toe walking, calf hypertrophy, and have difficulty climbing stairs.  By 8 years 
of age, most patients are losing the ability to rise from the floor and climb stairs, have an increasingly 
labored gait, and often fall while walking.  By 10 to 14 years of age, most are wheelchair-dependent.  
Upper limb, cardiac, and diaphragmatic muscles continue to progressively weaken during 
adolescence, and patients often require ventilation support in their teens.  In recent years, use of 
ventilation support and glucocorticoids have increased life span by several years (Kohler, 2009); 
however, DMD still has an early mortality rate of 100%.   
There is no cure for DMD and those drug treatments that have recently been approved for the disease, 
i.e., ataluren, which received conditional approval in the European Union, and eteplirsen 
(Exondys51™), which received accelerated approval in the United States, demonstrate limited 
efficacy and are appropriate for only a subset of patients.  Current standard of care guidelines include 
the administration of glucocorticoids (Birnkrant, 2018a; Birnkrant, 2018b), which can delay the time 
to respirator dependence and the onset of scoliosis, and improve performance on measures of clinical 
function in patients with DMD (Manzur, 2009).  However, they do not fully ameliorate symptoms or 
halt disease progression.  Moreover, their use is often limited by numerous side effects, including 
growth inhibition, delay of pubertal changes, weight gain, behavioral changes, osteoporosis resulting 
in fractures, Cushingoid facies and habitus, cataracts, and myopathy, a particularly serious concern 
for patients with DMD (Manzur, 2009; Schakman, 2009; Hanaoka, 2012).   
Thus, even though there are a handful of treatment options available, those options are inadequate and 
a significant need remains for safer and more effective treatments for patients affected by this fatal 
disease. 
Rationale for Edasalonexent as a Potential Therapy for the Treatment of DMD 
Edasalonexent, an orally administered small molecule containing covalently linked salicylic acid and 
docosahexaenoic acid (DHA), synergistically leverages the ability of both compounds to 
intracellularly inhibit activated nuclear factor kappa light chain enhancer of activated B cells 

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(NF-κB) to reduce NF-κB-mediated inflammation and muscle degeneration and facilitate muscle 
regeneration (Kopp, 1994; Yin, 1998; Cai, 2004; Zwart, 2010).  Following its cellular uptake, 
edasalonexent is hydrolyzed into its constituents by endogenous fatty acid amide hydrolase (FAAH), 
simultaneously delivering salicylic acid and DHA to key intracellular targets where they significantly 
inhibit activated NF-κB. 
In vitro, edasalonexent inhibits NF-κB and downstream cytokines known to be increased in DMD 
(Vu, 2016).  Edasalonexent inhibits lipopolysaccharide (LPS)-stimulated pro-inflammatory gene 
expression (TNFα, IL-6, IL-1β, SOCS3, MMP9) in RAW264.7 macrophages and this effect is greater 
than that produced by DHA or the combination of DHA and salicylic acid.  In addition, studies in 
mouse C2C12 myotubes showed that edasalonexent blocks cytokine-induced reductions in MyoD to 
a greater degree than dexamethasone and blunts cytokine-induced upregulation of MuRF1 and 
MMP9, both of which promote the degradation of key intracellular proteins and the extracellular 
matrix (Cai, 2004; Li, 2009).  These data are consistent with selective inhibition of activated NF-κB 
by edasalonexent having a more positive and favorable effect on muscle degeneration and 
regeneration than that produced by the concomitant NF-κB inhibition and activation of the 
glucocorticoid receptor by glucocorticoids.  
In vivo, edasalonexent inhibits NF-κB, and has positive effects in the mdx and golden retriever 
muscular dystrophy (GRMD) models of DMD.  Edasalonexent reduced LPS-stimulated release of 
TNFα levels in normal mice, and reduced muscle inflammation and muscle fiber degeneration, 
preserved muscle mass, and increased the number of regenerating fibers per field in the mdx mouse 
model of muscular dystrophy (Hammers, 2016).  Moreover, a single treatment with edasalonexent 
inhibited basal NF-κB p65 deoxyribonucleic acid (DNA) binding as well as LPS-stimulated NF-κB 
p65 activity and induction of TNFα protein in the GRMD dog model.  Similarly, administration of 
CAT-1041, a closely related analog of edasalonexent that differs only in the omega-3 fatty acid 
moiety, significantly improved muscle endurance, increased muscle mass, and reduced fibrosis in the 
mdx mouse, and improved pulmonary function in the GRMD model of DMD. 
By reducing inflammation and muscle degeneration while simultaneously facilitating muscle 
regeneration, pharmacological inhibition of NF-κB with edasalonexent has the potential to provide 
disease-modifying benefits to patients of all mutations beyond those afforded by glucocorticoids, but 
without their negative side effects, which are largely independent of their anti-inflammatory 
properties (Schacke, 2004; Newton, 2007).   
2.1. 
Summary of Edasalonexent Nonclinical Data 
In nonclinical studies, edasalonexent demonstrated reduction of NF-κB activation in vitro and in vivo, 
and disease-modifying effects in 2 established animal models of DMD, the mdx mouse and the 
GRMD models.  To support single- and repeat-dose oral administration in healthy subjects, 
edasalonexent has been assessed in a series of nonclinical studies including safety pharmacology, 
genotoxicity, and general toxicity studies in rats and dogs, with durations of repeat dose oral 
administration up to 6 and 9 months, respectively.   
Detailed information on all edasalonexent nonclinical studies conducted to date can be found in the 
Investigator’s Brochure. 

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2.2. 
Summary of Edasalonexent Clinical Experience 
Edasalonexent was evaluated in three Phase 1 studies in adults (Donovan, 2017). Across the 
3 studies, 79 adult subjects received single doses of edasalonexent up to 6000 mg and multiple doses 
up to 4000 mg/day for 14 days (~100 and 67 mg/kg/day, respectively), with no identified safety 
concerns.  Single-dose exposures of 2000 mg (~33 mg/kg) edasalonexent significantly reduced 
ex vivo LPS-stimulated NF-κB activity and NF-κB p65 DNA binding, while 14 days of dosing with 
edasalonexent reduced basal expression of NF-κB target genes in patients with type 2 diabetes with 
mild inflammation.   
Edasalonexent is currently being evaluated in ambulatory boys with DMD from ≥4 to <8.0 years of 
age at enrollment who are not receiving corticosteroids in a multipart, Phase 1/2 clinical study, 
CAT-1004-201.  Phase 1, which has been completed, was a 1-week, open-label study to assess the 
safety and pharmacokinetics (PK) of 3 sequential ascending doses (33, 67, or 100 mg/kg/day 
administered as 17 mg/kg twice daily [BID], 33 mg/kg BID, or 33 mg/kg TID) of edasalonexent 
under low- or high-fat conditions.  Results from Phase 1 indicate that 7 days of treatment with 
edasalonexent at doses up to 100 mg/kg/day were safe and generally well tolerated. There were no 
serious adverse events (SAEs), discontinuations, or dose reductions, and the most common adverse 
events (AEs) were gastrointestinal, primarily mild diarrhea.  Pharmacokinetic data collected showed 
daily exposures projected to be within the range observed in adults (on a mg/kg basis), with only 
modest differences between dosing after a high- or low-fat meal at the 67 mg/kg/day dose.  
Importantly, clinical exposure at 100 mg/kg/day was 4 times lower than exposures at the 
no-observed-adverse-effect level (NOAEL) in the 13-week postnatal day (PND) 21 rat study, and 
2 times lower than those at the NOAEL in the 13-week dog study.  
Phase 2, which has also been completed, included patients from Phase 1 as well as additional patients 
(total N = 31) and was a randomized, placebo-controlled study to evaluate the efficacy, safety, PK, 
and PD of the 2 higher doses edasalonexent (67 and 100 mg/kg/day) over 12 weeks.  Both doses were 
safe and generally well tolerated.  There were no dose-dependent safety findings and, as in Phase 1, 
the majority of AEs were mild in nature and the most common treatment-related AEs were 
gastrointestinal, primarily mild and transient diarrhea.  There were no treatment-related SAEs, drug 
discontinuations, or dose reductions, nor were there any concerning trends in chemistry, hematology, 
coagulation, or adrenal function assessments.  Edasalonexent plasma exposures were consistent with 
those observed in Phase 1.  The 100 mg/kg/day dose level demonstrated numerical improvement 
versus placebo across multiple efficacy measures, though not statistically significant.  The 
67 mg/kg/day dose group had mixed efficacy results compared with both the 100 mg/kg/day dose 
group and placebo, which in each case were not statistically significant.   
In the open-label extension, which is currently ongoing, all patients (including those who received 
placebo in Phase 2) were to receive open-label edasalonexent at dose levels of 67 or 100 mg/kg for up 
to 124 weeks.  Based on results from Phase 2 and the recommendation of the Data Safety Monitoring 
Board (DSMB), all patients in the 67 mg/kg/day dose group were switched to the 100 mg/kg/day dose 
group (which was already ongoing at the time the Phase 2 results were analyzed).   
In an interim analysis conducted with all data through December 31, 2017, patients on edasalonexent 
at 100 mg/kg/day over 60 weeks of treatment showed a slower decline in timed function test speeds 
(10-meter walk/run test [10MWT], 4-stair climb, and time to stand) and North Star Ambulatory 
Assessment (NSAA) when compared to declines in the prior off-treatment control period.  In addition 
to the muscle function assessments, supportive changes in measures of muscle health were observed, 

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consistent with positive edasalonexent treatment effects.  Four muscle enzymes (creatine kinase, 
alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase) were significantly 
lower compared to Baseline following 12 weeks of edasalonexent treatment and at later time points, 
consistent with a slowing of muscle degeneration and an improvement in muscle integrity.  A 
composite of magnetic resonance imaging (MRI) T2 rates of change in five lower leg muscles was 
also significantly improved through 48 weeks of 100 mg/kg/day edasalonexent treatment compared to 
the off-treatment control period, consistent with a reduction of inflammation in the muscle. 
Improvements were also seen in rates of change in both soleus and vastus lateralis magnetic 
resonance spectroscopy (MRS) fat fraction through 48 weeks of edasalonexent treatment compared to 
the off-treatment control period, consistent with a reduction of fat in the muscle.  Edasalonexent 
remained well tolerated and no safety signals were observed. The most common adverse events, 
gastrointestinal, were typically mild and transient.  Based on emerging safety and efficacy data, all 
patients moved to 133 mg/kg/day (33/33/67 mg/kg in 3 divided doses) in the open-label extension. 
As of June 2018, 32 pediatric patients had received up to 112 weeks of active dosing with 
edasalonexent at doses up to 133 mg/kg/day, with a total combined exposure of over 45 years, with 
no safety concerns.  More detailed information on clinical studies and potential clinical risks of 
edasalonexent can be found in the Investigator’s Brochure.   
2.3. 
Dose Selection Rationale 
Selection of the 100 mg/kg/day dose of edasalonexent for this Phase 3 study is supported by interim 
results from the ongoing Phase 1/2 study of edasalonexent in same aged boys with DMD 
(CAT-1001-201), which showed: 
• The plasma exposure of edasalonexent at the NOAEL in the 26-week rat study (2000 
mg/kg/day) is approximately 4-fold higher than that expected with the anticipated clinical 
dose utilized in CAT-1004-201 of 100 mg/kg/day.  The plasma exposure of edasalonexent 
at the NOAEL in the 13-week and 9-month dog studies (1000 mg/kg/day) is 
approximately 2-fold higher, than that expected with the anticipated clinical dose for this 
study of 100 mg/kg/day. 
• Treatment with edasalonexent at doses of 67 mg/kg/day for up to 47 weeks, at 
100 mg/kg/day for up to 84 weeks, and at 133 mg/kg/day for up to 32 weeks was safe and 
generally well tolerated with no dose-dependent safety findings, treatment-related SAEs, 
drug discontinuations, or dose reductions, and no concerning trends in chemistry, 
hematology, coagulation, or adrenal function assessments. 
• Treatment with 100 mg/kg/day edasalonexent resulted in numerical improvements across 
multiple efficacy measures compared to placebo.  In contrast, the 67 mg/kg/day dose 
group had mixed efficacy results compared with both the 100 mg/kg/day dose group and 
placebo.  Compared to declines in the prior off-treatment control period, patients on 100 
mg/kg/day edasalonexent showed a slower decline in timed function test speeds and 
NSAA scores over 60 weeks of treatment. 

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3. 
TRIAL OBJECTIVES 
3.1. 
Primary 
• To assess the efficacy of edasalonexent as measured by change from Baseline (CFB) on 
NSAA Total Score in pediatric patients with DMD  
3.2. 
Secondary 
• To assess the safety and tolerability of edasalonexent in pediatric patients with DMD  
• To assess the effects of edasalonexent on physical function as measured by the 10MWT, 
time to stand from supine, and the 4-stair climb in pediatric patients with DMD  
3.3. 
Overall Study Design 
This is a randomized, double-blind, placebo-controlled, Phase 3, multisite study of edasalonexent in 
pediatric patients with DMD.  Approximately 126 patients will be enrolled.   
Eligible patients will be ambulatory boys ≥4.0 to <8.0 years of age with a confirmed diagnosis of 
DMD who have not used steroids within 24 weeks prior to treatment initiation (Day 1).  In regions 
where eteplirsen is approved or there is an established access program, patients who have received at 
least 24 weeks of treatment with eteplirsen prior to Day 1 will be eligible for the study. 
As shown in Figure 1, this is a 52-week, double-blind, placebo-controlled study comparing one dose 
level of edasalonexent with placebo.   
Following completion of the treatment period and Primary Endpoint evaluation, patients may elect to 
continue in the open-label extension study, pending approval by appropriate ethics committees and 
regulatory authorities.  Patients who choose not to participate should complete the safety follow-up 
within 2 weeks of the last dose of study drug. 
Figure 1: 
CAT-1004-301 – Overview of Study Design 
 

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3.3.1. 
Double-Blind Placebo-Controlled Study Design 
As shown in Figure 1, following a Screening period to determine eligibility, approximately 
126 patients will be randomized 2:1 to receive edasalonexent 100 mg/kg/day (administered as 
approximately 33 mg/kg TID) or placebo in double-blind fashion daily for 52 weeks.  The exact 
capsule count per dose will be provided.  Randomization will be stratified by Baseline age (≤6.0 years 
or >6.0 years), time to stand from supine (≤5 seconds or >5 seconds), treatment with eteplirsen (yes 
or no), and region (North America or Europe/Asia/Australia). If siblings are enrolled, they will be 
assigned to the same treatment group. 
All Screening procedures will be performed within 4 weeks prior to the start of treatment (Day 1).  At 
the discretion of the Investigator, informed consent, collection of medical history and demographic 
data, and collection of laboratory Screening assessments may be completed remotely by a qualified 
medical professional at an alternative site setting.   
After Screening, eligible patients will complete Baseline procedures and begin receiving study drug 
(edasalonexent or placebo) on Day 1.  Study drug will be orally administered as soft-gel capsules in 
divided doses taken with food containing at least 8 grams of fat as detailed in Section 5.1.1.  Patients 
and their families will be provided with written and verbal instructions for study drug administration, 
and subsequent doses will be administered remotely, except for on scheduled site visits as specified in 
the Schedule of Assessments (SOA) in Appendix 1.  Nutritional guidance will be provided at 
Baseline.  Patient compliance with nutritional guidance will be confirmed throughout treatment.   
Efficacy and safety will be assessed at site visits at the timepoints specified in the SOA in 
Appendix 1.  Efficacy assessments will include: the NSAA; timed function tests (TFTs) including the 
10MWT, time to stand from supine, and the 4-stair climb; muscle strength testing; the Performance of 
Upper Limb (PUL) scale; and assessment of physical functioning as measured by the PODCI.   
Safety assessments will include collection of AEs, SAEs, growth parameters (height and weight), 
vital signs, physical examinations, clinical laboratory testing (including chemistry, hematology, and 
urinalysis), assessment of adrenal function (adrenocorticotrophic hormone [ACTH] and cortisol 
levels), and electrocardiogram (ECG).  To measure heart rate and heart rate variability, additional 
cardiac monitoring will be performed for approximately 48 hours via a wearable cardiac monitoring 
device if approved for use in the participating country. To measure bone health, lateral spine 
radiography and dual energy X-ray absorptiometry (DXA) scan will be performed if approved by the 
appropriate governing bodies at each site or country. 
For analysis of PK, blood and urine samples will be obtained for determination of edasalonexent and 
its metabolite concentrations.  Blood samples will be drawn for analysis of PD. 
To assess acceptability and palatability of edasalonexent, caregivers will complete a study drug 
questionnaire. 
A safety follow-up should occur within 2 weeks of the last dose of study drug for collection of AEs. 
3.3.2. 
Study Conduct during the COVID-19 Pandemic  
Ensuring the safety of patients is paramount especially during a pandemic so modifications have been 
made to the original study procedures and schedule of assessments to reduce the patient’s risk or 
exposure to COVID-19 while ensuring the integrity of the study. Changes to the study visit schedule 
which should be considered, or deemed necessary per the local situation at each site during the 

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COVID-19 pandemic are captured in Appendix 2. Patients may not be able to come on-site for visits 
as specified in Appendix 1 or patients may be able to come on-site for visits however for a reduced 
amount of time to minimize risk or exposure to COVID-19, so considerations for modifying the 
schedule of assessments are captured in Appendix 2.        
Investigators must document how restrictions or institutional requirements during the COVID-19 
pandemic led to the changes in study conduct and duration of those changes and indicate which 
patients were impacted and how those patients were impacted.    
3.3.3. 
Completion of a Patient’s Participation in the Study and Overall Study Completion 
3.3.3.1. 
Completion of a Patient’s Participation in the Study 
The length of a patient’s participation in the study will be from the time the informed consent form is 
signed through the Week 52 visit.  A patient will be considered to have completed the study when 
they have completed the Week 52 assessments.  Patients who do not participate in the open-label 
extension study will be considered to have completed the study after they complete the safety follow-
up.  
3.3.3.2. 
Premature Patient Discontinuation from the Study 
Parents/guardians and patients (as applicable according to site and regional regulations) are free to 
withdraw consent and/or discontinue participation in the study at any time, without prejudice to 
further treatment.  A patient’s participation in the study may also be discontinued at any time at the 
discretion of the Investigator, Medical Monitor, or Sponsor. 
The reasons indicated in Section 5.2.5 for withdrawing a patient from treatment may also be 
justifiable reasons for the Investigator, Medical Monitor, or Sponsor to remove a patient from the 
study.  Patients also may be discontinued from the study if the study is terminated by the Sponsor (see 
Section 10.3.5). 
Patients who are prematurely withdrawn from the study (i.e., those who leave the study prior to 
completing the Week 52 assessments) will be asked to complete an early termination (ET) visit prior 
to their last dose of study drug and are not permitted to re-enroll in the study.   
Post-study SAEs will be reported according to Section 7.6.  A patient will be considered discontinued 
due to an AE if they discontinued due to any AE, regardless of whether the AE is considered related 
to investigational product.  If the patient withdraws from the study due to an AE, the Investigator 
should arrange for the patient to be followed appropriately until the AE has resolved or stabilized (in 
the opinion of the Investigator). 
At the end of the patient’s participation in the study, the Investigator will document the reason(s) for 
study discontinuation in the electronic case report form (eCRF). 
3.3.3.3. 
Overall Study Completion 
The study will be considered complete when the last patient has completed their last assessment. 
3.4. 
Discussion of Study Design, Including Choice of Control Group 
This is a Phase 3 study to evaluate the efficacy, safety, PK, and PD of edasalonexent in ambulatory, 
male, pediatric patients with a confirmed diagnosis of DMD.  This is a randomized, double-blind, 

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placebo-controlled study in which patients will receive either edasalonexent or placebo daily for 
52 weeks.  
The rationale for the dose levels and dosing regimen used in the study is provided in Section 2.3. 
Population 
The study’s eligibility criteria are designed to include only patients with an established diagnosis of 
DMD who are sufficiently well (both in terms of DMD and in terms of concomitant illness) to safely 
participate in study procedures and provide interpretable results.  Diagnostic criteria will include 
demonstration of a classic DMD clinical phenotype, increased serum creatine kinase (CK), and the 
presence of a mutation in the dystrophin gene consistent with DMD. 
Eligible patients will be ambulatory boys ≥4.0 to <8.0 years of age.  These gender and age criteria are 
intended to facilitate enrollment (as DMD is much more common in boys), and ensure that the 
enrolled patients will be able to complete the timed function tests included in the study as efficacy 
assessments.  In addition, eligible patients must have not used steroids within the 24 weeks prior to 
initiation of study treatment (Day 1).  It is important to evaluate the effects of edasalonexent in the 
absence of concomitant steroid use since the positive effects of glucocorticoids are thought to be at 
least partially mediated by their anti-inflammatory action via modulation of NF-κB, and 
edasalonexent is proposed to work through the same pathway (but without the negative side effects).  
While it is also important to evaluate the efficacy and safety of edasalonexent in the absence of other 
disease-modifying therapies, recent nonclinical data have shown that administration of edasalonexent 
in combination with eteplirsen results in increased dystrophin expression and does not reveal any 
increased risk.  Therefore, patients who have received at least 24 weeks of treatment with eteplirsen 
prior to Day 1 will be eligible for the study.   
For detailed information on prohibited concomitant medications, please refer to Section 5.3.   
To minimize the risk for practice effects (which could mask potential treatment effects), decrease the 
heterogeneity of the patient population with respect to disease state, and ensure that patients are not at 
high risk for imminent loss of ambulation, patients will be required to do the following to enroll:  
stand from supine in ≤10 seconds, and complete the 10MWT and 4-stair climb. 
It is strongly recommended that all patients receive annual vaccinations for influenza virus. 
Safety Monitoring 
The safety measures used in this study are standard and reflect appropriate monitoring of pediatric 
patients receiving an investigational drug.  Although no adrenal abnormalities have been observed in 
the Phase 1/2 study, CAT-1004-201 (see the Investigator’s Brochure), since weight loss and adverse 
effects on adrenal glands were observed in 13-week juvenile rat toxicology studies at plasma 
exposures higher than anticipated in humans, monitoring of adrenal function will be included in this 
study as a precaution.  In addition to monitoring by the Investigators, sub-Investigators and Medical 
Monitors, a DSMB will provide oversight of the study. 
Efficacy 
The selection of efficacy endpoints was based on consideration of the primary clinical manifestations 
of DMD, namely a progressive loss of muscle strength and the associated impact of this loss on 
function.  The potential effects of edasalonexent on muscle strength and function are assessed by 

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means of widely used and accepted measures of these constructs including NSAA, TFTs, muscle 
strength testing, PUL entry item assessment, and the PODCI Transfer and Basic Mobility scale.   

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4. 
PATIENT POPULATION AND SELECTION 
4.1. 
Inclusion Criteria 
A patient must meet all the following criteria to be eligible for this study. 
1. Written consent/assent by patient and/or legal guardian as per regional and/or Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC) requirements  
2. Diagnosis of DMD based on a clinical phenotype with increased serum creatine kinase (CK) 
and documentation of mutation(s) in the dystrophin gene known to be associated with a DMD 
phenotype  
3. Male sex by birth 
4. Age ≥4.0 to <8.0 years (at the time of consent) 
5. Able to perform stand from supine without assistance in ≤10 seconds  
6. Able to perform the 10MWT and 4-stair climb 
7. Able to swallow placebo capsules at the Screening Visit 
8. Followed by a doctor or medical professional who coordinates Duchenne care on a regular 
basis and willingness to disclose patient's study participation with medical professionals 
4.2. 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study. 
1. Use of corticosteroids within 24 weeks prior to Day 1; use of inhaled, intranasal, and topical 
corticosteroids is permitted 
2. Use of an investigational drug, idebenone, or dystrophin-focused therapy within 4 weeks or a 
period of 5 half-lives duration prior to Day 1 (whichever is longer) or ongoing participation in 
any other therapeutic clinical trial.  Exception: Patients who have received at least 24 weeks of 
a stable dose of eteplirsen prior to Day 1, and expected to continue treatment, will be eligible.  
3. Use of the following within 4 weeks prior to Day 1: immunosuppressive therapy, warfarin, 
phenytoin, S mephenytoin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, alfentanil, 
pimozide, quinidine, sirolimus, tacrolimus, or paclitaxel 
4. Use of human growth hormone within 3 months prior to Day 1 
5. Documented positive hepatitis B surface antigen, hepatitis C antibody, or human 
immunodeficiency virus (HIV) or a known risk factor for hepatitis such as a blood transfusion 
within 12 weeks prior to Day 1 
6. Hemoglobin <10.5 g/dL 
7. Abnormal gamma glutamyl transferase (GGT) (>laboratory’s upper limit of normal [ULN]) 
8. Other prior or ongoing medical condition, known hypersensitivity to omega 3 fatty acids, 
physical findings, ECG findings, or laboratory abnormality (including but not limited to renal 
insufficiency or impaired hepatic function) that, in the Investigator’s opinion, could adversely 
affect the safety of the patient, make it unlikely that the course of treatment or follow up 

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would be completed, or impair the assessment of study results (e.g., a gastrointestinal 
condition that would impair fat absorption) 
9. In the Investigator’s opinion, unwilling or unable for any reason (e.g., attentional or 
behavioral issues) to complete all study assessments and laboratory tests and comply with 
scheduled visits, administration of drug, and all other study procedures 
Note:  Patients may be re-tested or re-screened for eligibility after discussion with the Medical 
Monitor. 

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5. 
TREATMENTS 
5.1. 
Treatments Administered 
5.1.1. 
Double-Blind Placebo-Controlled Treatment 
Eligible patients will be randomly assigned 2:1 to receive either edasalonexent 100 mg/kg/day 
(administered as approximately 33 mg/kg TID) or placebo in double-blind fashion daily for 52 weeks.  
The exact capsule count per dose will be provided.  All doses of study drug will be orally 
administered in divided doses with food containing at least 8 grams of fat.  Nutritional guidance will 
be provided at Baseline.  Patient compliance with the nutritional guidance will be confirmed 
throughout treatment.  The acceptability and palatability of edasalonexent will be explored in this 
study; data will be collected from patients and caregivers. 
5.1.2. 
Investigational Product(s) Description 
Description of edasalonexent capsules: 
• 100-mg capsules (Size 3 oval) containing 100 mg edasalonexent formulated with the 
following excipients: polysorbate-80, glyceryl monooleate (type 40), PEG-400, and dl-
alpha-tocopherol, with imprint “####” using black iron oxide ink   
• 250-mg capsules (Size 7.5 oval) containing 250 mg edasalonexent formulated with the 
following excipients: polysorbate-80, glyceryl monooleate (type 40), PEG-400, and dl-
alpha-tocopherol, with imprint “####” using black iron oxide ink   
Description of placebo capsules: 
• Placebo 100-mg match capsules (Size 3 oval) containing the following excipients:  
polysorbate-80, glyceryl monooleate (type 40), PEG-400, and dl-alpha-tocopherol, with 
imprint “####” using black iron oxide ink 
• Placebo 250-mg match capsules (Size 7.5 oval) containing the following excipients:  
polysorbate-80, glyceryl monooleate (type 40), PEG-400, and dl-alpha-tocopherol, with 
imprint “####” using black iron oxide ink 
5.1.3. 
Packaging and Labeling 
The investigational products described in Section 5.1.2 will be provided to the site by the Sponsor or 
designee.  Refer to the Study Drug Handling Manual (SDHM) for additional details.  The Sponsor or 
designee will provide the Investigator with packaged investigational product labeled in accordance 
with country-specific regulatory requirements. 
5.1.4. 
Storage 
The investigational products must be stored refrigerated at 2°C to 8°C (36°F to 46°F) at the site.  
Single bottles dispensed to patients may be stored at up to 25°C (77°F; controlled room temperature) 
for up to 30 days.  Refer to the SDHM for additional details. 
5.1.5. 
Preparation and Administration 
Refer to the SDHM for additional details.   

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5.2. 
Dosing Considerations 
5.2.1. 
Dose Selection Rationale 
See Section 2.3 for details on dose rationale. 
5.2.2. 
Dose Modification or Reduction 
Temporary or persistent dose reductions may be made for safety or tolerability at any time during the 
study.  Refer to Section 7.9 for additional details. 
5.2.3. 
Safety Monitoring 
Safety will be monitored on an ongoing basis by the Investigator, Medical Monitor, and Sponsor.  In 
addition, the DSMB will review relevant study data (as defined in the DSMB charter) to decide on 
the continuation, termination, or modification of the trial (also see Section 8.4).   
5.2.4. 
Treatment Compliance  
Throughout the study, patients and their parents/caregivers will complete a diary documenting 
investigational product administration, and diet compliance.  Upon completion of data entry, the 
database will undergo a quality review to ensure acceptable accuracy and completeness.  In addition, 
site calls, which will occur throughout the study as noted in the SOA (Appendix 1), will include a 
compliance check on investigational product administration and diet.  Detailed information regarding 
the study-specific dietary requirements and the process for monitoring compliance to the diet are 
provided in the Study Reference Manual (SRM). 
5.2.5. 
Treatment Discontinuation 
A patient’s study treatment may be discontinued at any time at the patient’s/parent/legal guardian’s 
request or at the discretion of the Investigator, Medical Monitor or Sponsor.  The following may be 
justifiable reasons for the Investigator, Medical Monitor or Sponsor to discontinue a patient from 
treatment: 
• The patient experiences an intolerable or unacceptable AE 
• The patient is unable to comply with the requirements of the protocol 
• The patient participates in another investigational study without the written authorization 
of the Sponsor 
Discontinuation of treatment does not imply withdrawal from the study.   
Patients who discontinue treatment prematurely will be asked to complete the early termination visit 
prior to their last dose of study drug as noted in the SOA in Appendix 1.   
5.3. 
Prior and Concomitant Medications and Therapeutic Procedures 
In general, disease-modifying drugs, investigational drugs, immunosuppressive therapy, and drugs 
with narrow therapeutic indices metabolized by CYP3A4, CYP2C8, CYP2C9, and CYP2C19 are 
prohibited for at least 4 weeks prior to Day 1 and during the study (Table 2).  Recent nonclinical data 
have shown that administration of edasalonexent in combination with eteplirsen results in increased 
dystrophin expression and does not reveal any increased risk.  In regions where eteplirsen is approved 

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or there is an established access program, patients who have received at least 24 weeks of treatment 
with eteplirsen prior to Day 1 will be eligible for the study.   
Throughout the study, Investigators may prescribe concomitant medications or treatments deemed 
necessary to provide adequate supportive care to patients.   
Treatment with corticosteroids is prohibited within 24 weeks prior to Day 1 and during the study 
(Table 2).   
All medications should be taken as prescribed, per Investigator judgment, even when blood samples 
are planned to be drawn.  In addition, all concomitant medications, including supplements must be 
recorded in the source documentation and in the eCRF.   
Note:  Annual vaccination for influenza is strongly recommended for all patients. 
Table 2: 
Prohibited Prior and Concomitant Medications 
Medication 
Prohibited within 
24 weeks prior to Day 1 
Prohibited within 
4 weeks prior to Day 1a 
Initiation prohibited 
throughout the study 
Corticosteroids b 
X 
X 
X 
Deflazacort (Emflaza™) 
X 
X 
X 
Ataluren (Translarna™) 
 
X 
X 
Idebenone (Raxone®) 
 
X 
X 
Other investigational drugs 
 
X 
X 
Immunosuppressive therapy 
 
X 
X 
Warfarin, phenytoin, 
S mephenytoin, cyclosporine, 
dihydroergotamine, ergotamine, 
fentanyl, alfentanil, pimozide, 
quinidine, sirolimus, tacrolimus, 
paclitaxel 
 
X 
X 
 Eteplirsen (Exondys 51™) c 
 
 
X 
a 
If 5 half-lives of the drug is >4 weeks, drug is prohibited for 5 half-lives prior to Day 1. 
b       Use of inhaled, intranasal, and topical corticosteroids is permitted. 
c       Use of eteplirsen is permitted if on a stable dose for at least 24 weeks prior to Day 1. 
5.4. 
Method of Assigning Patients to Treatment 
During the study, patients will be randomly assigned in a 2:1 ratio to receive edasalonexent or 
placebo in double-blind fashion.   
5.5. 
Blinding and Randomization 
5.5.1. 
Blinding and Randomization 
Approximately 126 patients will be randomized 2:1 to receive edasalonexent or placebo in double-
blind fashion daily for 52 weeks.  Randomization will be stratified by Baseline age (≤6.0 years or 
>6.0 years), time to stand from supine (≤5 seconds or >5 seconds), treatment with eteplirsen (yes or 
no), and region (North America or Europe/Asia/Australia). 

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If siblings are enrolled, only one sibling will be included in the Randomized Population, the second 
sibling will be assigned to the same treatment group as the randomized sibling (see Section 9.3).  If 
both siblings meet the inclusion/exclusion criteria, the sibling to be included in the Randomized 
Population will be the first sibling randomized. 
5.5.2. 
Scheduled Unblinding 
After completion of the study, patients, monitors, Investigators, study center personnel, and the 
Sponsor will remain blinded to treatment assignments until results from the study are available.   
5.5.3. 
Emergency Unblinding 
Prior to scheduled unblinding (see Section 5.5.2), if an emergency where the identity of the 
investigational product must be known by the Investigator to provide appropriate medical treatment 
occurs, the Investigator will be allowed to unblind using the Interactive Web Response System 
(IWRS).  Before doing this, the Investigator should make every effort to discuss the situation with the 
Medical Monitor. 
The treatment assignment should only be unblinded when knowledge of the treatment assignment 
will impact the clinical management of the patient.  Every reasonable attempt should be made to 
complete the final treatment assessment procedures prior to unblinding, as knowledge of the 
treatment assignment could influence patient assessment.   

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6. 
STUDY ASSESSMENTS 
6.1. 
Study Schedule of Events 
The SOA for the study is provided in Appendix 1. 
The modified SOA for this study during the COVID-19 pandemic is provided in Appendix 2. 
6.2. 
Screening and Baseline Assessments and Start of Treatment 
Once written informed consent, and when appropriate, written assent is obtained, patients will be 
screened for eligibility for entry into the study based on the inclusion and exclusion criteria detailed 
in Sections 4.1 and 4.2.  A full medical/surgical history will be obtained, including information 
relating to any prior or existing medical conditions/surgical procedures that may be relevant to the 
patient’s experience in the study.  Demographic data and DMD-specific medical history information 
will also be recorded.  Patients will undergo a full physical examination, including vital signs (see 
Sections 6.4.1 and 6.4.2), safety labs, a 12-lead ECG tracing will be obtained, and body weight will 
be measured.  Additional cardiac monitoring will be performed via a wearable cardiac monitoring 
device to measure heart rate and heart rate variability if approved for use in the country.  The 
laboratory assessments shown in Appendix 3 will be performed.   
Screening assessments should be completed within 4 weeks of Day 1. 
At Baseline, patient eligibility for the study will be reconfirmed and the patient will be randomized.  
Patients will undergo a full physical examination.  Height and body weight will be measured and 
body mass index (BMI) will be calculated.  Any AEs or changes in concomitant medications since 
Screening will be recorded.  Patients will undergo Baseline efficacy evaluations as specified in 
Appendix 1, and blood samples will be drawn for safety, ACTH/cortisol, biomarkers and gene 
expression.  Bone evaluations (spine radiography and DXA scan) will be performed if approved by 
the appropriate governing bodies at each site or country.  Patients and their families will be provided 
with written and verbal instructions for study drug administration.  Nutritional guidance will also be 
given and study drug will be dispensed. 
6.3. 
Efficacy Assessments 
Efficacy will be assessed at the timepoints specified in Appendix 1.  
6.3.1. 
North Star Ambulatory Assessment (NSAA) 
The NSAA is a clinician-reported outcome instrument designed to measure ambulatory function in 
males with DMD (Scott, 2012).  During this assessment, patients are asked to perform 17 different 
functional activities, including a 10MWT, rising from supine, rising from a sit to stand, standing on 
1 leg, e.g., climbing and descending a step, rising from the floor, lifting the head, standing on heels, 
and jumping.  The NSAA has undergone detailed psychometric evaluations based on traditional 
(reliability and validity) and modern (Rasch analysis) methods, and has been included in international 
clinical trials (Kinali, 2009).  In addition, 36-month longitudinal data are available in patients with 
DMD (Mazzone, 2011; Pane, 2014b).  The NSAA will be administered by trained evaluators; every 
effort will be made to have the same evaluator perform all assessments for a given child at the same 
time of day.  Completion of this test is expected to take approximately 20-30 minutes. 

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Additional details on the performance of the NSAA are provided in the Clinical Evaluator Manual. 
6.3.2. 
Timed Function Testing  
TFTs will include the 10MWT and the stand from supine (as measured in the NSAA) as well as the 
4-stair climb.  These tests have been used as clinical trial endpoints in DMD and have shown 
response to therapeutic intervention with steroids (Mendell, 1989; Griggs, 1990; Beenakker, 2005; 
Manzur, 2009).  TFTs will be performed by trained evaluators; every effort will be made to have the 
same evaluator perform all assessments for a given child at the same time of day.  Completion of 
TFTs is expected to take approximately 10 minutes. 
Additional details on the performance of the TFTs is provided in the Clinical Evaluator Manual. 
6.3.3. 
Muscle Strength Testing 
Muscle strength testing will include assessment of knee extension and elbow flexion.  Muscle testing 
will be performed using a hand-held dynamometer.  Knee myometry will be performed while the 
patient is in a sitting position.  Elbow myometry will be performed while the patient is positioned 
supine.  Muscle testing will be performed by trained evaluators; every effort will be made to have the 
same evaluator perform all assessments for a given child at the same time of day.  Completion of each 
muscle test is expected to take approximately 10-15 minutes, for a total of 20-30 minutes.   
Additional details on the assessment of muscle strength are provided in the Clinical Evaluator 
Manual. 
6.3.4. 
Performance of Upper Limb (PUL) Scale 
The PUL was specifically designed by an international Clinical Outcomes Group consisting of 
clinicians, scientists, patient advocacy groups and industries representative to assess upper limb 
function in ambulant and non-ambulant DMD patients (Mercuri, 2012; Mayhew, 2013b).  The PUL is 
made up of a 6-point entry item (based on the modified Brooke Upper Extremity Scale) to define the 
starting functional level, and 22 items subdivided into shoulder level (6 items), middle level (9 items) 
and distal level (7 items) dimension (Pane, 2018).  Loss of full overhead reach occurs at median age 
9.6 with some boys losing the ability as early as age 5 or 6 (McDonald, 2018).  Patients will perform 
the PUL entry item assessment as specified in Appendix 1.  Based on the age of patients in this study, 
most patients will score a 6 on the 6-point entry item assessment.  Those patients who score a 6 on the 
6-point entry item assessment will not be required to perform the additional items.  Patients who 
score below a 6 on the 6-point entry item assessment will perform a subset of the PUL battery 
including the shoulder level dimension and supination, consisting of 7 items with a maximum score 
of 14.  In boys with DMD, the PUL has robust internal reliability, validity, and hierarchical 
scalability (Mayhew, 2013a), excellent interobserver and intra-observer reliability (Pane, 2014a), and 
is sensitive to changes over time (Seferian, 2015) and in response to steroid treatment (Pane, 2015).  
It may be most suitable for DMD patients 5 years of age and above.  Completion of the 6-point entry 
item assessment is expected to take approximately 5 minutes. Completion of the battery of PUL 
assessments is expected to take approximately 20 minutes.  
Additional details on the PUL scale are provided in the Clinical Evaluator Manual. 

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6.3.5. 
The Pediatric Outcomes Data Collection Instrument (PODCI) 
The PODCI is a well-validated tool for assessment of health-related functioning in children, and has 
been used in a study of boys with DMD (Henricson, 2013).  It is designed to be completed by the 
parent/caregiver of children aged 10 or younger, contains 86 questions, takes approximately 
20-30 minutes to complete, and provides information on the following 6 scales:  
• Upper Extremity and Physical Function Scale:  Measures difficulty encountered in 
performing daily personal care and student activities. 
• Transfer and Basic Mobility Scale:  Measures difficulty experienced in performing routine 
motion and motor activities in daily activities. 
• Sports and Physical Functioning Scale:  Measures difficulty or limitations encountered in 
participating in more active activities or sports.   
• Pain/Comfort Scale:  Measures the level of pain experienced during the past week. 
• Happiness Scale:  Measures overall satisfaction with personal looks and sense of 
similarity to friends and others of own age. 
• Global Functioning Scale:  A general combined scale calculated from the first 4 scales 
listed above. 
Parents/caregivers will complete the PODCI listed in Appendix 5 at timepoints listed in Appendix 1. 
6.3.6. 
Assessor Training and Ensuring Compliance with Protocol-Specified Test-
Administration. 
The following efficacy assessments will be administered by trained evaluators:  NSAA, TFTs, muscle 
strength testing, and PUL.  To help ensure proper and consistent test administration across 
evaluators/sites, all evaluators will undergo training on the proper administration of these assessments 
prior to the study.  As part of this training, therapists will administer each assessment to boys with 
DMD who are not participating in the study; test administrations will be videotaped, reviewed for 
adherence and inter-rater consistency, and feedback will be provided as applicable. 
To help ensure proper and consistent test administration over the course of the study, administration 
of NSAA, TFTs, and muscle strength testing may be videotaped and reviewed for each patient at 
Screening and Week 52 and may also be required at Baseline as specified in Appendix 1. 
Additional information on the training and monitoring of the administration of these tests is provided 
in the Clinical Evaluator Manual.  
6.4. 
Safety Assessments 
Safety will be assessed for all enrolled patients from Screening through the safety follow-up, as 
specified in Appendix 1.  Safety parameters include physical examinations, growth parameters, vital 
signs, clinical laboratory tests (including chemistry, hematology, urinalysis, and tests for adrenal 
function), ECGs, and concomitant medication monitoring as described in Section 6.4.5 and AEs as 
described in Section 7.  A list of all required clinical laboratory assessments is provided in 
Appendix 3.   

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6.4.1. 
Physical Examination and Growth Parameters 
The physical examinations will include an assessment of the patient’s general appearance; skin; head, 
ears, eyes, nose, throat (HEENT); lymph nodes; heart; lungs; abdomen; extremities/joints; and 
neurological and mental status.  Physical examinations should be performed by the same person when 
possible.  Height and weight will be measured at the timepoints specified in Appendix 1 and BMI 
will be calculated. 
6.4.2. 
Vital Signs 
Vital signs (blood pressure, heart rate, respiratory rate, and temperature) will be measured at the 
timepoints specified in Appendix 1.  Systolic and diastolic blood pressure (preferably assessed on the 
same arm each time) will be measured only after the patient is positioned in a semi-supine position 
and resting for at least 5 minutes.   
6.4.3. 
Clinical Laboratory Tests 
Blood and urine samples will be collected for clinical laboratory evaluations (see Appendix 3 for a 
complete list of analytes). 
The clinical laboratory tests to be done at Screening include hematology with differential, chemistry, 
and urinalysis.   
Blood samples for ACTH and cortisol will be obtained at Baseline before initiation of treatment.   
Chemistry, hematology, and ACTH/cortisol assessments done during the treatment period will be 
performed in the morning when possible.   
A central laboratory will provide collection supplies, arrange collection, and perform analysis of 
clinical laboratory evaluations indicated in Appendix 3.  Using the central laboratory for unscheduled 
clinical laboratory evaluations and repeat testing is recommended.  Procedures for the handling and 
shipment of all central laboratory samples will be included in the Laboratory Manual.  Specimens 
will be appropriately processed by the central laboratory facility and laboratory reports will be made 
available to the Investigator in a timely manner to ensure appropriate clinical review. 
The enrolling Investigator is responsible for reviewing and signing all laboratory reports unless the 
patient is transferred to another site for all subsequent visits.  The clinical significance of each value 
outside of reference range will be assessed by the Investigator and documented as either not clinically 
significant (NCS) or clinically significant.  All clinically significant values require a comment and the 
out-of-range value or the overlying diagnosis (or value if the diagnosis is unknown) must be captured 
as an AE. 
Clinical laboratory reports will serve as source documents. 
6.4.4. 
Electrocardiogram 
The 12-lead ECGs will be performed only after the patient is positioned supine, resting, and quiet for 
a minimum of 5 minutes.  If findings are abnormal, the Investigator is responsible for indicating 

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whether the ECG tracing is NCS or clinically significant.  In addition, ECGs will be centrally 
evaluated.   
6.4.5. 
Concomitant Medications and Therapies 
Concomitant medications and therapies are to be assessed at all visits.  Reasonable efforts will be 
made to determine all treatments (pharmacological and non-pharmacological) received by the patient.   
A medication/therapy is considered concomitant if it is taken/administered at any time from 
Screening through the final study evaluation. 
Data on pharmacological and non-pharmacological treatments will be recorded on an eCRF page, to 
include:  drug name/name of procedure, dose, route, regimen, start date, stop date, and indication.  At 
each study visit, the parent or caregiver will be asked about any additional treatments or any changes 
in regimen or dosages since the last visit.  Indications for any new medications or therapies during the 
study period will be recorded as an AE. 
Patients and their parents/caregivers will be contacted by the site between scheduled visits to assess 
concomitant medications and AEs (as indicated in Appendix 1). 
For detailed information on prohibited concomitant medications please refer to Section 5.3.   
6.5. 
Pharmacokinetic Assessments 
Samples for determination of edasalonexent and its metabolite concentrations will be drawn at 
selected visits as detailed in Appendix 1.  
In addition to the PK analyses described, any of the collected PK plasma and urine samples from 
study patients may also be used for profiling of drug binding proteins, bioanalytical method 
validation purposes, stability assessments, metabolite assessments, or to assess other actions of study 
drug with plasma constituents. 
6.6. 
Pharmacodynamic Assessments 
Blood samples will be obtained at selected visits as indicated in Appendix 1.  Assessments may 
include: 
• Circulating protein biomarkers to evaluate course of disease and/or response to treatment 
• DNA, RNA (ribonucleic acid), and micro-RNA samples may be collected and used for 
pharmacogenomic analyses that might predict the course of disease and/or responses to 
treatment as well as analysis of drug metabolizing enzyme and/or transporters. 
Details of blood collection procedures will be provided in the Laboratory Manual.   
6.7. 
Cardiac Monitoring 
Patients with DMD are known to have resting tachycardia even in the age range in this clinical study 
(Thomas, 2012).  Additionally, decreases in heart rate variability have been observed (Thomas, 
2015).  Since decreases in heart rate to age-normative values were observed in a previous clinical 
study (CAT-1004-201), measures of heart rate and variability will be collected for approximately 48 
hours via a wearable cardiac monitoring device if approved for use in the participating country. In 
addition, the results from the patient’s last cardiac assessment should be documented as part of 

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medical history. Prospective cardiac assessments performed should also be documented as part of 
ongoing procedures. 
6.8. 
Bone Evaluations 
Patients with DMD have a deficiency of bone mineral density and increased incidence of bone 
fractures which becomes more severe when taking corticosteroids.  Patients who use corticosteroids 
have over two times as many fractures as steroid naïve patients (King, 2007).  Fractures that occur in 
lower extremities can lead to early loss of ambulation.  Bone evaluations will be performed through 
lateral thoracolumbar spine radiography and DXA scan.  In Germany, bone assessment will not be 
performed until the respective approvals from the German Federal Office for Radiation Protection 
(Bundesamt für Strahlenschutz) become available.  A qualified medical professional will review the 
results of the lateral thoracolumbar spine radiography and DXA scan and designate the findings as 
normal or abnormal; if abnormal, the Investigator will indicate whether the scans are NCS or 
clinically significant.  In addition, bone radiography will be centrally evaluated.  
6.9. 
Study Drug Acceptability 
To evaluate the acceptability and palatability of edasalonexent, caregivers will complete the study 
drug questionnaire listed in Appendix 4  at timepoints indicated in Appendix 1.  
6.10. 
Total Volume of Blood Collected 
The total number of venipunctures and the total volume of blood collected during the study will be 
limited to that needed for safety monitoring, PK, and PD measurement.  Refer to the SRM and/or 
laboratory manual for the collection preparation and procedures as well as the estimated total volume 
of blood to be collected during the study.  The total blood volume collected from each patient for the 
entire study is within the guidelines set forth by the World Health Organization (WHO) (Howie, 
2011). 

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7. 
ADVERSE EVENTS AND ADVERSE EVENT REPORTING 
At each study visit, patients will be evaluated for new AEs and the status of existing AEs.  The 
Investigator may elicit symptoms using an open-ended question, followed by appropriate questions 
that clarify the patient’s verbatim description of AEs or change in concomitant medications.  The 
enrolling Investigator is responsible for safety oversight of data for all visits unless the patient is 
transferred to another site for all subsequent visits.  All AEs from the time of signing the informed 
consent through follow-up will be recorded on the eCRF. 
7.1. 
Timeframe for Collection of Adverse Events 
7.1.1. 
Adverse Events Occurring Prior to Study Treatment 
All AEs that occur between the time informed consent is provided and the patient’s receipt of the first 
dose of investigational product will be considered pretreatment AEs. 
7.1.2. 
Adverse Events Occurring After Study Treatment 
All AEs that occur from the time of the administration of the first dose of investigational product 
through the end of the safety follow-up will be considered treatment-emergent AEs (TEAEs).  
7.1.3. 
Adverse Events Occurring Following Patient Discontinuation of Treatment 
For patients who prematurely discontinue study treatment (see Section 5.2.5), but who are not 
withdrawn from the study, AEs will continue to be recorded until the patient completes the study (see 
Section 3.3.3.1 for definition of patient completion).  See Section 7.6 for reporting requirements after 
the patient completes the study. 
7.2. 
Definitions 
7.2.1. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation patient, which does not 
necessarily have a causal relationship with the investigational product (active or placebo drug, 
biologic, or device).  An AE can, therefore, be any unfavorable and unintended symptom, sign, 
disease or condition, or test abnormality, whether considered related to the investigational product. 
Adverse events include: 
• Symptoms described by the patient or signs observed by the Investigator or medical staff 
• Test abnormalities (laboratory tests, ECG, X-rays, etc.) that result in an alteration in 
medical care (diagnostic or therapeutic) 
Adverse events do not include: 
• Changes that are characteristic of disease progression in Duchenne 
Abnormalities present at Baseline are considered AEs only if they reoccur after resolution or they 
worsen during the study. 

Clinical Trial Protocol:  CAT-1004-301 
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40 
7.2.2. 
Definition of a Serious Adverse Event 
Seriousness of an AE serves as a guide for defining regulatory reporting obligations.  An SAE is any 
AE that results in any of the following: 
Death:  The patient died as the result of the event. 
Life-threatening event:  Any AE that places the patient, in the view of the Investigator, at immediate 
risk of death from the AE as it occurred, i.e., does not include an AE that had it occurred in a more 
severe form, might have caused death. 
Required or prolonged inpatient hospitalization:  The AE resulted in an initial inpatient 
hospitalization or prolonged an existing hospitalization of the patient.  Note:  Planned hospital 
admissions, or surgical procedures for an illness or disease that existed before the administration of 
the study treatment or before the patient was enrolled in the study, will not be captured as SAEs 
unless they occur at a time other than the planned date. 
Persistent or significant disability/incapacity:  An AE that results in a substantial disruption of a 
person’s ability to conduct normal life functions. 
Congenital anomaly/birth defect:  A congenital anomaly/birth defect that occurs in the offspring of a 
patient exposed to the investigational product. 
Important medical events:  An AE that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, the event 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
7.3. 
Evaluation of Adverse Events/Serious Adverse Events 
7.3.1. 
Relationship to Study Treatment 
Assessment of the association between the AE and study drug exposure is important for regulatory 
reporting.  For each AE/SAE, the Investigator will determine whether there is a reasonable possibility 
that the AE may have been caused by the study drug according to the following categories: 
Not Related:  The AE is clearly not related to study drug. 
Unlikely Related:  There is no evidence of a causal relationship between study drug and the AE; 
although such relationship cannot be ruled out. 
Possibly Related:  There is some evidence supporting the possibility of a causal relationship between 
study drug and the AE. 
Related:  There is strong evidence that there is a causal relationship between study drug and the AE. 
A relationship to the investigational product must be given for each AE/SAE recorded, even if there 
is only limited information at the time.  The Investigator may change his/her opinion of causality in 
light of follow-up information, amending the AE/SAE report accordingly. 
7.3.2. 
Severity Grading of Adverse Event Scoring 
Note that severity is not the same as “seriousness,” which is defined in Section 7.2.2.   

Clinical Trial Protocol:  CAT-1004-301 
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The Investigator will grade the severity of all AEs/SAEs as mild, moderate, or severe, based on the 
following definitions (developed from Clinical Data Interchange Standards Consortium [CDISC] 
Study Data Tabulation Model [SDTM] standard terminology v3.1.1): 
Mild:  An AE that is usually transient and may require only minimal treatment or therapeutic 
intervention.  The event does not generally interfere with usual activities of daily living. 
Moderate:  An AE that is usually alleviated with specific therapeutic intervention.  The event 
interferes with usual activities of daily living, causing discomfort, but poses no significant or 
permanent risk of harm to the research participant. 
Severe:  An AE that interrupts usual activities of daily living, or significantly affects clinical status, or 
may require intensive therapeutic intervention. 
7.3.3. 
Outcome 
Outcome describes the status of the AE.  The Investigator will provide information regarding the 
patient outcome of each AE. 
Possible results of an AE outcome are defined as follows: 
Fatal:  The termination of life as a result of an AE. 
Not recovered/not resolved:  The patient has not recuperated or the AE has not improved. 
Recovering/resolving:  The patient is recuperating or the AE is improving. 
Recovered/resolved:  The patient has recuperated or the AE has resolved. 
Recovered with sequelae/resolved with sequelae:  The AE has resolved, but the patient has been left 
with symptoms or pathology. 
Unknown:  Not known, not observed, not recorded, or refused. 
7.3.4. 
Action Taken Regarding the Investigational Product 
The Investigator will be required to provide the action taken regarding investigational product (e.g., 
active, comparator) in response to the AE according to the following categories: 
Dose not changed:  No change in administration of the investigational product. 
Dose reduced:  Reduction in the frequency, strength or amount of investigational product 
administered. 
Drug (investigational product) interrupted:  Temporary interruption (termination) in administration of 
the investigational product. 
Drug (investigational product) withdrawn:  Administration of the investigational product terminated 
(no further dosing). 
Not applicable:  Determination of a value is not relevant in the current context. 
Unknown:  Not known, not observed, not recorded, or refused. 

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Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary 
43 
any safety alert notifications for onward submission to their local IRB/IEC as required.  All reports 
sent to Investigators will be blinded. 
The Investigator must continue to follow the patient until the SAE has resolved or until the condition 
becomes chronic in nature, stabilizes (in the case of persistent impairment) or the patient dies.  Within 
24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation (e.g., patient 
discharge summary or autopsy reports) to contacts above via fax or e-mail.  If it is not possible to 
access the EDC system, refer to the procedures outlined above for initial reporting of SAEs.   
7.7. 
Follow-up of Adverse Events/Serious Adverse Events 
All AEs/SAEs documented at a previous visit/contact that are designated as not recovered/not 
resolved or recovering/resolving will be reviewed by the Investigator at subsequent visits/contacts. 
All AEs will be followed until the parameter returns to its Baseline status, resolution of AE, 
completion of the patient’s participation, agreement is reached between the Investigator and Sponsor 
that the event no longer requires follow-up, or study termination, whichever occurs first.  SAEs will 
be followed until resolution, the condition stabilizes, or the Investigator and Medical Monitor agree 
that follow-up is no longer necessary.  Rules for AE/SAE follow-up apply to all patients, including 
those withdrawn prematurely to the extent allowed by the patient’s consent.  The Investigator will 
ensure that follow-up includes further investigations consistent with appropriate medical management 
and patient consent to elucidate the nature and/or causality of the AE/SAE. 
7.8. 
Pregnancy Reporting 
Not applicable for this study. 
7.9. 
Temporary or Persistent Dose Reductions 
Temporary or persistent dose reductions may be made for safety or tolerability reasons in the 
judgment of the Principal Investigator.  If at any time after initiation of treatment the patient 
experiences a clinically significant AE indicative of drug intolerance, the patient will undergo clinical 
assessment as soon as reasonably possible.  The Principal Investigator should discuss any potential 
dose modifications or reduction with the Medical Monitor.   
7.10. 
Monitoring of Abnormal Laboratory Values 
Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are common in 
patients with DMD, so exclusion of patients with abnormal Baseline values is not feasible.  Patients 
with abnormal GGT will be excluded.   
During the study, liver function tests will be monitored, including ALT, AST, GGT, alkaline 
phosphatase, glutamate dehydrogenase, and bilirubin.  If increases in ALT or AST are noted, the 
relationship of these to CK will be determined, as well as to GGT and measures of liver synthetic 
function.  Trends in these parameters will be monitored.  Safety alert flags for the Investigator and 
Medical Monitor will include an alert for increases in ALT >150 U/L with stable or decreased CK, as 
well as for total bilirubin, glutamate dehydrogenase, or GGT parameters greater than the ULN.   
Additional information on safety alert flags will be included in the Laboratory Manual.   

Clinical Trial Protocol:  CAT-1004-301 
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7.11. 
Stopping Rules 
Either the Investigator or Medical Monitor may stop dosing in individual patients based on 
tolerability or AEs. 
7.12. 
Restriction on the Lifestyle of Patients 
Not applicable. 

Clinical Trial Protocol:  CAT-1004-301 
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8. 
DATA COLLECTION, QUALITY ASSURANCE, AND 
MANAGEMENT 
8.1. 
Recording of Data 
The Investigator must provide the Sponsor or its designee direct access to each patient’s source 
documents.  Source documents may include, but are not limited to, the following original documents, 
data, and records where information is first recorded. 
• Hospital records 
• Medical histories and narrative statements relating to the patient’s progress 
• Clinical and office charts (electronic or paper) 
• Operative reports 
• Laboratory notes/reports 
• Project-specific worksheets (e.g., for study visits), including all worksheets developed 
specifically for this study 
• X-ray, MRI, and computed tomography (CT) reports 
• Cardiac ultrasound, echocardiogram 
Required data for this study will be captured using eCRFs via EDC unless otherwise specified in this 
document, below. 
Clinical data that are not recorded on the eCRF will be captured and transferred to the Sponsor or its 
designee. 
8.2. 
Data Quality Assurance 
The eCRFs will be reviewed by the Sponsor’s clinical monitor or designee for completeness and 
accuracy.  Source document verification will be performed.  The data will also be reviewed internally 
by the Sponsor’s Data Management department or its designee and, if necessary, the investigational 
sites will be queried for corrections and/or clarifications.  Upon completion of data entry and 
reconciliation, all EDC user access privileges will be changed to read only.  Upon completion of data 
entry, the database will undergo a quality review to ensure acceptable accuracy and completeness.   
8.3. 
Data Management 
The format and content of the eCRF will be approved by the Sponsor or its designee prior to the start 
of the study.  The Sponsor or its designee will be responsible for database creation, data entry if 
applicable, and management of data from sources other than the clinical database (e.g., laboratory 
data).  Once all patients have completed all study visits, the database will be cleaned, locked, 
unblinded and the statistical analysis will be performed. 
8.4. 
Data Safety Monitoring Board 
External oversight for this trial will be provided by a DSMB, which will include physicians 
experienced in treating DMD and a biostatistician experienced in clinical trials.  The primary 

Clinical Trial Protocol:  CAT-1004-301 
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responsibility of the DSMB is to protect the safety and welfare of patients participating in this clinical 
trial and to ensure the integrity of the clinical trial.   
Specifically, for this study, the DSMB will be responsible for examining accumulated safety data, 
PK, and compliance data to make recommendations concerning the continuation, termination, or 
modification of the trial based on the safety of the interventions under study throughout the study.  
The DSMB will meet with a frequency as defined in the DSMB charter. 
Further information regarding the DSMB review process will be provided in the DSMB charter. 

Clinical Trial Protocol:  CAT-1004-301 
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9. 
STATISTICAL METHODS AND PLANNED ANALYSES 
9.1. 
General Considerations 
A Statistical Analysis Plan (SAP), in compliance with the International Council for Harmonisation 
(ICH) and Food and Drug Administration’s Guidance for Industry: “Statistical Principles for Clinical 
Trials”, will be written and finalized prior to database lock and unblinding providing greater detail on 
the statistical analysis methodology. 
All eCRF data, as well as any outcomes derived from the data, will be displayed in data listings.   
Descriptive characteristics for continuous variables will be summarized using mean, median, standard 
deviation, minimum and maximum values.  For categorical variables, the number and percentage of 
patients (or observations) will be reported.  
Unless otherwise defined for a particular endpoint, a patient’s baseline value is the last measurement 
prior to initiation of study drug. 
9.2. 
Determination of Sample Size 
Approximately 126 patients will be enrolled and assigned to either edasalonexent or placebo in a 
2:1 ratio.  Based on Phase 1/2 data of changes in NSAA in this age group, an effect size of 0.625 is 
assumed.  With this effect size, and assuming a dropout rate of approximately 20%, the study has 
approximately 80% power to show a difference between the treatment groups at a 2-sided type I error 
rate of 0.05.   
The number of enrolled patients on eteplirsen should not exceed their representation in the Duchenne 
population. 
9.3. 
Analysis Sets  
The following are the analysis populations for this study: 
Randomized Population:  The Randomized Population consists of all patients who are randomized 
into the study.  
Note: If a randomized patient has a sibling assigned to the same treatment group, the non-randomized 
sibling (i.e., the sibling assigned to the same treatment as the randomized sibling) will not be included 
in the randomized population (see Section 5.5.1).   
Safety Population:  The Safety Population will consist of all patients who receive at least 1 dose of 
study drug.  This will include the set of patients who were assigned the same treatment as their 
randomized sibling.   
Full Analysis Population:  The Full Analysis Population for efficacy analyses will be a modified 
intent to treat (mITT) population and will consist of all patients in the Randomized Population who 
receive at least 1 dose of study drug, and provide at least 1 valid post Baseline NSAA efficacy 
assessment.   
Per Protocol Population:  The Per Protocol (PP) Population will consist of all patients in the Full 
Analysis Population who complete the study, without any significant protocol violations.   

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PK Population:  The PK Population will consist of all patients in the Safety Population who receive at 
least 1 dose of edasalonexent and have at least 1 measured plasma concentration.   
Other analysis populations may be defined in the SAP.   
9.4. 
Demographics and Baseline Characteristics 
Demographics, including age at Baseline considered as a continuous variable, frequency of age by 
year, age at Baseline (≤6.0 years or >6.0 years) and Baseline characteristics, including time to stand 
from supine (≤5 seconds or >5 seconds) treatment with eteplirsen (yes or no), and region (North 
America or Europe/Asia/Australia) will be listed by patient, and summarized by treatment group and 
overall.   
9.5. 
Concomitant Medications 
Concomitant medications will be listed by treatment and coded using the WHO Drug dictionary.  
9.6. 
Medical History 
Medical history will be listed and coded by patient using the Medical Dictionary for Regulatory 
Activities (MedDRA®) dictionary Version 21.0. 
9.7. 
DMD-Specific Medical History 
DMD-specific medical history, including age at symptom onset and diagnosis, will be listed by 
patient, and summarized by treatment group and overall.   
9.8. 
Patient Disposition 
All patients who sign the informed consent will be included in a summary(s) of patient disposition.  
The number of patients randomized, and the number and percentage of patients discontinuing and 
completing treatment, will be presented.  The number of patients discontinuing before study 
completion (including reason for discontinuation), and the number of patients completing the study 
will be presented as well.  The number and percentage of patients in the various analysis populations 
will be presented separately. 
9.9. 
Study Treatment Usage and Compliance 
For the Safety Population, treatment duration, number of administrations, and compliance will be 
summarized by treatment group and overall.   
9.10. 
Efficacy Analyses 
Results of efficacy assessments will be listed by patient, and summarized by treatment group and 
timepoint, as applicable.  For the TFTs, both the times to complete in seconds and their speed (i.e., 
the reciprocals) will be tabulated (in the case of the 10MWT, in units of 10 meters per second; in the 
case of the stand from supine and 4-stair climb in units of task per second).  Descriptive statistics will 
be calculated for quantitative efficacy data as well as for the CFB, and differences between groups as 
applicable. 

Clinical Trial Protocol:  CAT-1004-301 
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9.10.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint will be the CFB in the NSAA Total Score at Week 52. 
The CFB in NSAA Total Score will be analyzed using a mixed-model repeated-measures (MMRM) 
analysis of covariance (ANCOVA), implemented using SAS® Proc Mixed.  The factors in the model 
will be Baseline age (≤6.0 years or >6.0 years), time to stand from supine (≤5 seconds or >5 seconds), 
region (North America or Europe/Asia/Australia), visit, treatment group, Baseline value, Baseline 
value by visit, and treatment group by visit. 
The primary analysis will test the treatment difference at Week 52 via the MMRM model at the two-
sided 0.05 level.  Details of the MMRM model will be provided in the SAP. The primary analysis 
will be performed on the Full Analysis Population with exclusions that may be defined in the SAP, 
such as excluding patients receiving treatment with eteplirsen. 
9.10.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints will be the CFB to Week 52 on the 10MWT, stand from supine, 
and 4-stair climb. 
The Baseline values and CFB in each will be summarized by treatment group and timepoint using 
descriptive statistics.  The CFB will be analyzed using the same MMRM ANCOVA model as 
described above for the primary efficacy endpoint. The secondary efficacy analyses will be performed 
on the Full Analysis Population with exclusions that may be defined in the SAP, such as excluding 
patients receiving treatment with eteplirsen. 
9.10.3. 
Controlling for Multiplicity 
The method for controlling the overall Type I Family-wise error rate at the two-sided 0.05 level will 
be provided in the SAP. 
9.10.4. 
Sensitivity Analyses of the Primary and Secondary Efficacy Endpoints 
Sensitivity analyses of the primary and secondary efficacy endpoints will be specified in the SAP.   
While the MMRM analysis represents the primary method for incorporating patients with missing 
data (i.e., observed case analyses), a multiple imputation method for addressing missing data will be 
applied using the primary and secondary analysis methods.   
Additional details on the methods to assess the impact of missing data will be provided in the SAP. 
9.10.5. 
Additional Efficacy Endpoints 
Additional efficacy endpoints will include CFB on the following endpoints: 
• Muscle strength testing  
• PUL entry item assessment 
• PODCI Transfer and Basic Mobility scale 
The analysis methods for these endpoints will be defined in the SAP.  Additional efficacy endpoints 
may also be defined in the SAP. 

Clinical Trial Protocol:  CAT-1004-301 
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9.11. 
Pharmacokinetic Analyses 
Serial plasma concentration time data collected for edasalonexent and its metabolites will be analyzed 
using non-compartmental methods for all patients with evaluable data.  Actual sample and dosing 
times will be used for pharmacokinetic analyses. Pharmacokinetic parameters, as data permit, will be 
reported for individual patients and summarized using descriptive statistics by visit. Trough 
concentrations will be summarized separately, along with other single time-point plasma 
concentration data by visit. Exploratory PK-PD analyses may be performed as deemed necessary. 
In addition to non-compartmental analyses or when the data do not lend to a non-compartmental 
approach, pharmacokinetic data will be analyzed using non-linear mixed-effects modeling approach 
for population pharmacokinetic analyses. For population PK analyses, data from this clinical study 
will be pooled with data from other clinical studies with extensive and/or sparse sampling. The 
population PK analyses will characterize the inter- and intra-subject variability in pharmacokinetic 
parameters and evaluate the effect of covariates such as but not limited to, demographics (e.g., age, 
body weight, race), disease status on oral clearance and volume. Exploratory population PK-PD 
analyses may also be performed to evaluate and characterize exposure-response relationships. 
As an exploratory analysis, urine samples will be analyzed in terms of concentrations of 
edasalonexent and/or metabolites. 
Raw and derived data will be summarized using descriptive statistics and presented graphically, as 
appropriate.  Plasma PK parameters will be estimated from plasma concentration-versus-time data 
using noncompartmental analyses.   
The following noncompartmental PK parameters will be calculated from plasma samples: 
• Area under concentration time curve from time 0 to time of last quantifiable concentration 
(AUClast) 
• Area under concentration time curve from time 0 to 4 hours post dosing (AUC0-4) 
• Maximum plasma concentration (Cmax) 
• Last quantifiable plasma concentration (Clast) 
• Time of Cmax (Tmax) 
• Time of Clast (Tlast) 
• Time between the time of dosing and time of appearance of plasma concentration (Tlag) 
The detailed methodology will be described in the SAP. 
9.12. 
Safety Analyses 
Safety will be assessed using the incidence of treatment-emergent AEs and SAEs, physical 
examination findings, growth parameters, vital signs, clinical laboratory evaluations, and ECGs.   
Results of all safety assessments will be listed by patient, and summarized by treatment group and 
timepoint as applicable.  
These safety analyses will be compared qualitatively between groups; however, there will be no 
inferential statistical comparisons between groups. 

Clinical Trial Protocol:  CAT-1004-301 
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9.12.1. 
Physical Examination, Growth Parameters, Electrocardiograms, and Vital Signs 
Physical examination (general appearance, skin, HEENT, etc.) abnormal results will be summarized.  
Physical examination results will also be summarized in a shift table from Baseline. 
Growth parameters (height, weight, BMI) will be compared to age-normative percentiles. 
ECG results will be summarized at each timepoint, and also using shift tables from Baseline. 
Vital signs (temperature, heart rate, respiratory rate, and systolic and diastolic blood pressure), and 
changes from Baseline in vital signs, will be summarized descriptively at Baseline and other study 
timepoints.  Data listings will be provided. 
9.12.2. 
Clinical Laboratory Tests 
Values at all study timepoints and changes from Baseline to post Baseline timepoints in clinical 
chemistry, hematology and urinalysis results will be summarized descriptively.  Shift tables from 
Baseline to each timepoint and from Baseline to each patient’s final visit will be produced by cohort 
and overall.   
Abnormal clinical laboratory values will be identified as outside (above or below) the normal range 
and will be evaluated for clinically notable abnormalities.  Reference (normal) ranges for laboratory 
parameters will be included in the clinical study report.   
9.12.3. 
Adverse Events 
Adverse events will be coded using the MedDRA® dictionary and will be categorized by system 
organ class (SOC) and preferred term.  
An overall summary of TEAEs will include the number and percentage of patients in each cohort and 
overall reporting: 
• Any TEAEs 
• Treatment-related TEAEs 
• Severe TEAEs 
• Serious TEAEs, including any events resulting in death 
• Treatment-related serious TEAEs 
• TEAEs (and treatment-related TEAEs) leading to discontinuation of study drug 
TEAEs will be summarized by SOC and preferred term, with each patient counted only once for each 
AE reporting level.  TEAEs will also be summarized by SOC, preferred term, and severity and by 
SOC, preferred term, and relatedness.  The most severe occurrence of a TEAE, as well as the most 
extreme relationship of the TEAE to the study procedures or treatment, will be used in tabulations of 
severity and relatedness in cases of multiple occurrences of the same TEAE.   
9.13. 
Pharmacodynamic Analyses 
Pharmacodynamic analyses may include evaluation of gene expression as well as circulating protein 
and micro-RNA biomarkers that help inform target engagement and efficacy.  These will be assessed 
at the times specified in Appendix 1.  Blood samples will also be collected at times specified in 

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Appendix 1  for pharmacogenomic studies that might predict the course of disease and/or response to 
treatment as well as analysis of drug metabolizing enzyme and/or transporters.   
9.14. 
Cardiac Monitoring 
Measures of cardiac autonomic dysfunction, including heart rate variability, will be measured at the 
times specified in Appendix 1. Results will be summarized by treatment group and timepoint as 
applicable.  
The detailed analyses will be provided in the SAP. 
9.15. 
Bone Evaluations 
Lateral thoracolumbar spine radiography scans and DXA scans will be performed at the times 
specified in Appendix 1. Bone radiography will be locally read and centrally evaluated. 
Results will be summarized by treatment group and timepoint as applicable.  
The detailed analyses will be provided in the SAP. 
9.16. 
Other Statistical Issues 
9.16.1. 
Missing or Invalid Data 
For the primary and secondary efficacy analyses, the MMRM analyses will be observed case 
analyses.  Multiple imputation will be used as a sensitivity analysis to address missing data (see 
Section 9.10.4); additional methods will be specified in the SAP.  
If a patient is not able to complete a TFT, a value of 0 tasks/second will be assigned. 
If a patient initiates corticosteroid therapy or discontinues study treatment, all observations from a 
patient after these events will be censored from the primary and secondary efficacy analyses.  
Sensitivity analyses which incorporate these observations will be defined in the SAP. 
9.16.2. 
Multisite Issues   
Summary statistics for the primary and secondary efficacy endpoints will be presented by 
investigative site. 
9.16.3. 
Subgroup Analyses 
The SAP will address analyses of additional subgroups. 

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10. 
SPECIAL REQUIREMENTS AND PROCEDURES 
This protocol was designed and will be conducted, recorded, and reported in compliance with the 
ICH/Good Clinical Practice (GCP) guideline.  These requirements are stated in the ICH Guideline 
Topic E6 entitled “Guideline for Good Clinical Practice”. 
10.1. 
Institutional and Ethics Review 
This protocol and a patient informed consent form, participant-facing information sheets, and any 
proposed advertising materials, must be reviewed and approved by an IRB/IEC, applicable regulatory 
authorities, and host institution(s) for written approval (where applicable) before enrollment of 
patients and release of investigational product.  Documentation of IRB/IEC approval and the 
approved consent form must be received by the Sponsor or its designee prior to obtaining the 
patient’s informed consent.  These documents will also be submitted to and approved by the above 
parties for all substantial amendments to the original approved documents, where applicable. 
10.2. 
Changes to the Conduct of the Study or Protocol 
Any changes in the study protocol, such as changes in the study design, objectives or endpoints, 
inclusion and exclusion criteria, and/or procedures (except to eliminate an immediate hazard) will be 
implemented only after the mutual agreement of the Investigator and the Sponsor or designee.  All 
protocol changes must be documented in protocol amendment(s).  Protocol amendment(s) must be 
signed by the Investigator and approved by the IRB/IEC and Competent Authorities (CA), if 
applicable, prior to implementation.  Any changes in study conduct that result from a pending 
amendment will be considered protocol deviations until required IRB/IEC/CA approvals are granted.  
Documentation of IRB/IEC/CA approval (as applicable) must be returned to the Sponsor or designee.  
10.3. 
Investigator’s Responsibilities 
10.3.1. 
Patient Informed Consent 
Investigators must adhere to GCP, which includes ethical principles that have their origin in the 
Declaration of Helsinki, when developing the patient informed consent form and when obtaining 
consent from the patient.  Written informed consent from the parent or legal guardian of the patient 
(and written assent for pediatric patients as per regional and/or IRB/IEC requirements) is required 
prior to enrollment in the study.  It is the responsibility of the Investigator to document the consent 
process within the source documents and obtain consent using an IRB-/IEC-approved consent form. 
10.3.2. 
Case Report Forms 
Copies of pertinent records relevant to the study, including all source documents, will be made 
available to the Sponsor or its designee on request with due precaution towards protecting the privacy 
of the patient. 
Data will be entered by the site onto the eCRFs in the EDC system.  Unless explicitly directed, blank 
data fields are not acceptable.  Any erroneous entries made on the eCRFs should be corrected.  
Changes made to the data after initial entry into the eCRF will be captured via an electronic audit 
trail, and should include the reason for change.  Incomplete entries or entries needing additional 
explanation will be highlighted or queried to the Investigator for clarification. 

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10.3.3. 
Record Retention 
The enrolling Investigator is responsible for oversight and maintenance of the study records and 
patient source documents unless the patient is transferred to another site for all subsequent visits.  
These records must be readily available for audit or inspection. 
The Investigator must retain study records for at least 2 years after the last marketing approval has 
been granted, or at least 2 years have elapsed since the formal discontinuation of clinical program.  
However, these documents should be retained for a longer period, if required by other applicable 
requirements (e.g., applicable local regulatory requirement) or by an agreement with the Sponsor or 
its designee.  The Investigator should contact the Sponsor or its designee prior to any record 
destruction. 
Patient records or other source data must be kept for the maximum period of time mandated by the 
hospital, institution, or private practice, but not less than 15 years. 
If off-site archiving is used, all records should be retrieved and made available for review at the time 
of an audit or regulatory authority inspection. 
10.3.4. 
Monitoring 
A representative of the Sponsor or its designee will visit the Investigator periodically for the purpose 
of monitoring the progress of this study in accordance with the protocol, GCP, and local regulations.  
Noncompliance with the protocol, GCP, and local regulations will be documented and corrective 
actions implemented, as necessary.  It is the responsibility of the Investigator to be present or 
available for consultation during monitoring visits.  During these routine visits, all data pertaining to a 
patient’s participation in this clinical investigation must be made available to the monitor. 
Monitoring during the COVID-19 pandemic is subject to Investigator and/or local restrictions. It is 
possible that after local restrictions are lifted, monitoring may resume with more intense pace to clean 
all data accumulated during the pandemic.   
At any time prior to, during, or after completion of the clinical study, an audit may be performed by 
the Sponsor or its designee or a representative of a national regulatory agency may choose to inspect 
a study site.  Investigators should notify the Sponsor or its designee upon notification of inspection by 
a representative of a national regulatory agency.  A Sponsor or designee representative will be 
available to assist in the preparation for study site inspections.  All pertinent study data should be 
made available for verification, audit, or inspection purposes. 
10.3.5. 
Study or Site Termination 
If the Sponsor, the Investigator, or regulatory authorities discover any conditions during the study that 
indicate that the study or study site should be terminated, this action may be taken after appropriate 
consultation between the Sponsor and the Investigator.  The Sponsor has the right to terminate the 
participation of either an individual site or the study at any time, for any reason, which may include 
the following: 
• The incidence and severity of AEs in this or other studies indicates a potential health 
hazard to patients 
• Patient enrollment is unsatisfactory 

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• Data recording is inaccurate or incomplete. 
• Investigator(s) does not adhere to the protocol or applicable regulatory guidelines in 
conducting this study 
• Submission of knowingly false information from the study site to the Sponsor or 
regulatory authorities 
In the event that the study is terminated early, the Sponsor will provide specific guidance to 
investigational sites regarding the end-of-study procedures. 
10.3.6. 
Investigational Product Control 
10.3.6.1. Receipt of Investigational Product 
A proof of receipt, which details the quantity and description of the investigational product, will 
accompany the shipment from the Sponsor or designee to the Investigator.  The site must 
acknowledge each shipment of investigational product in the IWRS system once received. The 
Investigator must ensure that the investigational product is maintained in a controlled location, with 
limited access, and under adequate storage conditions (as described in Section 5.1.4). 
10.3.6.2. Disposition of Unused Investigational Product 
All unused investigational products must be maintained under adequate storage conditions in a 
limited-access area.  If any unused material is remaining upon completion of the study, the material 
will be returned to the Sponsor or destroyed only after the following has been completed: 
• Accountability has been performed by a representative of the Sponsor. 
• Approval to return or destroy unused Investigational Product.  Refer to the SDHM for 
further details. 
10.3.6.3. Product Handling and Complaints Reporting 
If there are any issues during the study related to the quality of the Investigational Product, the 
clinical site pharmacist or pharmacy designee should contact the Sponsor. 
10.3.7. 
Disclosure of Data 
All details related to the disclosure and publication of study data will be addressed in the 
Investigator’s study contract.   
10.3.8. 
Confidentiality and Data Privacy    
Personal data recorded on all documents will be regarded as strictly confidential and will be handled 
and stored in accordance with the General Data Protection Regulation (GDPR 25May2018) in 
European Union Member States.  
Sponsor affirms the patient's right to protection against invasion of privacy and to be in compliance 
with ICH and other local regulations (whichever is more stringent). Sponsor requires the Investigator 
to permit sponsor representatives (monitor) and when necessary, representatives from regulatory 
authorities, to review and/or copy any medical records relevant to the study in accordance with local 
laws (any copies of patients’ records must be duly anonymised to protect patients’ confidentiality).  

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Should direct access to medical records require a waiver or authorisation separate from the patient’s 
statement of informed consent, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual. Representative of the sponsor may be required to have access 
to patient’s medical records for quality assurance purposes but patients should be reassured that their 
confidentiality will be respected at all times.  
Representative of sponsor must maintain the confidentiality of all patient’s data and will not disclosed 
information by which patients may be identified to any third party other than those directly involved 
in the treatment and organization for which the patient has given explicit consent for data transfer. 

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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
 
Screen a 
BL b 
Double Blind, Placebo-Controlled Treatment (Weeks 1 - 52) 
Safety F/U c 
Study Week(s) 
-4 - 0 
0 
6 
13 
19 
26 
32 
39 
45 
52/ETd  
 
Informed Consent/Assent 
X 
 
 
 
 
 
 
 
 
 
 
Site Visit e  
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Site Call e, f 
 
 
X 
 
X 
 
X 
 
X 
 
X 
Med History/Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Confirm Eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
Randomization g 
 
X 
 
 
 
 
 
 
 
 
 
Vital Signs  
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Weight  
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Height 
 
X 
 
 
 
X 
 
 
 
X 
 
Physical Examination 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
AEs/Con Medsh  
X 
Continuous 
12-Lead ECGi  
X 
 
 
 
 
X 
 
 
 
X 
 
Cardiac Monitoring j 
X 
 
 
 
 
X 
 
 
 
X 
 
Hematology/Chemistry k 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
ACTH/Cortisol k  
 
X 
 
X 
 
X 
 
X 
 
X 
 
Urinalysis  
X 
 
 
 
 
X 
 
 
 
X 
 
DNA Sample l 
 
X 
 
 
 
 
 
 
 
 
 
Biomarkers, Gene Expression k 
 
X 
 
X 
 
X 
 
X 
 
X 
 
NSAA, Stand from Supine, 10MWT, 
4-Stair Climb, Muscle Strength m 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
PUL n 
 
X 
 
 
 
X 
 
 
 
X 
 
Videotape Functional Assessments o 
X 
X 
 
 
 
 
 
 
 
X 
 
PODCI p 
 
X 
 
 
 
 
 
 
 
X 
 
Lateral Spinal Radiography, DXA q 
 
X 
 
 
 
 
 
 
 
X 
 
Study Drug Questionnaire 
 
 
 
 
 
X 
 
 
 
 
 
Nutritional Guidance r 
 
X 
 
 
 
 
 
 
 
 
 
Drug Dispensation  
 
X 
 
X 
 
X 
 
X 
 
 
 
Drug Accountability 
 
 
 
X 
 
X 
 
X 
 
X 
 
PK (plasma and urine) s 
 
 
 
X 
 
X 
 
 
 
X 
 
 
a Per Investigator’s discretion, informed consent, medical history/demographic data and lab assessments may be completed remotely by a qualified medical professional. 
b The first day of study drug is “Day 1”; unless otherwise specified, all assessments should be completed within a 4 week window prior to Day 1. 
c Safety follow-up should occur within 2 wks. after last dose of study drug.  Patients continuing in the open-label extension study are not required to perform the safety follow-up. 
d If patient discontinues treatment early, patient will be asked to return for early termination (ET) visit prior to their last dose of study drug.  Functional assessments performed 
within 6 weeks of discontinuing treatment do not need to be repeated at the ET visit.  If the ET visit occurs after drug has been discontinued, certain assessments may be omitted 
per Sponsor discretion. 

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e Weeks 6-19 should be conducted within the study week with a ±4-day window.  Weeks 26-54 have a ±10-day window. 
, f Per Investigator discretion, site calls may occur by telephone or use of other technology. 
g Randomization occurs after Screening assessments have been completed and eligibility is confirmed. 
h AEs and concomitant medication/therapy will be assessed at all visits and during site calls. 
i ECGs will be performed predose at all timepoints. At Week 26, ECG will per performed predose and 2 hours postdose (+/-15 min). 
j Cardiac monitoring will be performed for approximately 48 hours remotely via a wearable cardiac monitoring device if approved for use in the participating country. 
k Blood samples will be drawn in the morning when possible.  
l DNA sample may be collected at Baseline for drug metabolizing enzyme and/or transporter analysis as well as pharmacogenomic analysis of potential markers of clinical 
risk/benefit. 
m Assessments should be performed in the order listed and in the morning when possible.  Time to stand from supine and 10MWT will be recorded as measured in the NSAA.  
n The PUL 6-point entry item scale will be performed at all timepoints.  If a patient scores a 6 on the PUL entry item scale, no further PUL testing is required for the visit. 
o  Videotaping at Baseline is required if Screening video did not pass QC.   
p PODCI will be performed when feasible. 
q These assessments should be collected within 2 months prior to Day 1. In Germany, bone assessment will not be performed until the respective approvals from the German 
Federal Office for Radiation Protection (Bundesamt für Strahlenschutz) become available. 
r Patient compliance with the nutritional guidance will be confirmed throughout the trial. 
s Urine PK collection will be performed at Week 13.  Plasma PK collection will be performed predose at Week 13 and Week 52.  At Week 26 plasma PK collection will be 
performed predose, 1 hour (+/- 5 min), 2 hours (+/-15 min), and 4 hours (+/- 15 min) postdose.

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APPENDIX 2. POTENTIAL MODIFICATIONS TO THE SCHEDULE OF 
ASSESSMENTS DURING THE COVID-19 PANDEMIC 
At the time of the COVID-19 pandemic, all enrolled patients had completed at least Week 26 so 
the implementation of alternative means to complete study assessments is intended for Week 39 
and Week 52 only.  
If the Investigator is able to perform the scheduled visit without impact to the safety of the 
patients and their families because of the COVID-19 pandemic, the Investigator should perform 
study assessments on site according to Appendix 1.   
If the Investigator is unable or unwilling to perform the scheduled Week 52 visit within window 
without impact to the safety of the patients and their families because of the COVID-19 
pandemic, the Investigator, along with the patient/caregiver may decide to conduct the visit out 
of window (but in no case should the projected target date be changed by more than 2 months).    
The COVID-19 pandemic has impacted study sites variably, so individual situations at each site 
may impact the capabilities of sites to perform certain study assessments.  The purpose of 
Appendix 2 is to outline considerations for sites to perform study procedures either on site or 
remotely by using alternative approaches to collect study assessments.  While some study 
assessments can be performed remotely, it is acknowledged that others are not feasible to be 
conducted remotely. 
As the top priority is safety, assessing for AE and concomitant medications is the highest priority 
to continue, which will occur remotely at intervals specified in Appendix 1.  Based on the safety 
profile of edasalonexent to date, and consideration that all patients in this study have been on 
study drug for 6 months, other safety assessments, including physical examinations, chemistry 
and hematology labs and urinalysis can be deferred for six-month intervals if not feasible given 
the COVID-19 pandemic.   
The next priority is study integrity, which requires continued administration of study drug and 
efficacy assessments.  Drug dispensation can take place according to local site procedures, 
including secured, temperature-controlled shipments to the patients’ homes.  Study drug 
accountability can be assessed remotely as well.   
Remote collection of efficacy measurements may occur if not feasible on site. Efficacy 
measurements collected remotely will be administered and monitored by trained evaluators. 
Additional details on the remote collection of efficacy measurements are provided in the Remote 
Efficacy Assessment Clinical Evaluator Manual developed for Duchenne clinical trials during 
the COVID-19 pandemic.  Functional assessments may be limited by the remote testing 
environment.  
Some study assessments from Appendix 1 may be not included in Appendix 2 due to the 
Sponsor’s assessment of patient safety vs. criticality during the COVID-19 pandemic.   
In the situation where the Investigator is able to perform study procedures on site but requires 
prioritization of study assessments to minimize patient time on site or exposure to certain 
locations within the study location, the Investigator should prioritize according to the outline 

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below. If a prioritized assessment cannot be performed, that does not preclude other assessments 
for the specific Visit in Appendix 1 if feasible and without additional risk.  
 
• Week 39 Visit: performed on-site, priorities listed below 
− Assess AE and Concomitant Medications 
− Measure weight (to re-supply study drug), perform study drug accountability, re-
supply Study Drug 
− Perform Primary and Secondary Efficacy Assessments (NSAA, TFTs, PUL) 
− Physical examination and vital signs 
− Lab assessments:  chemistry, hematology, UA and PK (drawn at the same time) 
• Week 39 Visit: on-site visit is cancelled, priorities listed below 
− Reconsent/assent for remote efficacy assessments  
− Assess AE and Concomitant Medications 
− Measure weight by home scale (to re-supply study drug), assess drug 
accountability as appropriate, re-supply Study Drug via courier service 
− Perform Primary and Secondary Efficacy Assessments (NSAA, TFTs, PUL) 
remotely requires videotaping. More detail can be found in the Remote Efficacy 
Assessment Clinical Evaluator Manual 
• Week 52 Visit: performed on-site, priorities listed below 
− Assess AE and Concomitant Medications 
− Perform Primary and Secondary Efficacy Assessments (NSAA, TFTs, PUL) 
− Physical examination and vital signs, including height and weight 
− Lab assessments:  chemistry, hematology, UA and PK and biomarkers (drawn at 
the same time) 
− ECG 
− PODCI (if time limitations, provide and collect at next opportunity) 
− DXA and lateral spine films (recognizing that traveling to other parts of the clinic 
or hospital) may not be conducive at this time) 
• Week 52 Visit: on-site visit is cancelled, priorities listed below 
− Reconsent/assent for remote efficacy assessments  
− Assess AE and Concomitant Medications 
− Perform Primary and Secondary Efficacy Assessments (NSAA, TFTs, PUL) 
remotely requires videotaping. More detail can be found in the Remote Efficacy 
Assessment Clinical Evaluator Manual 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary  
64 
− Measure weight by home scale and height as feasible.  
− Perform drug accountability as appropriate 
− Lab assessments:  chemistry, hematology, UA to be considered via local labs but 
defer to Investigators’ judgement and interval since most recent assessments 
− PODCI (provide electronically and collect at next opportunity 
 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary  
65 
APPENDIX 3. LIST OF CLINICAL LABORATORY ASSESSMENTS  
For timing of laboratory assessments, see Schedule of Assessments in Appendix 1   
Clinical Safety Assessments 
Clinical Chemistry 
Urinalysis 
Hematology 
Sodium 
Potassium 
Chloride 
Bicarbonate 
Total protein 
Albumin 
Creatine kinase  
Calcium 
Phosphorus 
Glucose 
Blood urea nitrogen 
Creatinine 
Uric Acid 
Lactate dehydrogenase 
Total bilirubin (direct if above ULN) 
Alkaline phosphatase 
AST 
ALT 
GGT 
Cystatin C 
Cortisol (AM) 
ACTH 
Glutamate dehydrogenase 
Specific gravity 
pH 
Protein 
Glucose 
Ketones 
Bilirubin 
Blood 
RBCs 
WBCs 
Epithelial cells 
Bacteria 
Casts 
Crystals 
WBC count 
RBC count 
Hemoglobin 
Hematocrit 
MCV, MCH, and MCHC 
Platelet count 
WBC differential (% and 
absolute) 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
 
 
ACTH=adrenocorticotropic hormone; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
GGT=gamma-glutamyl transferase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; ULN=upper level of normal; WBC=white blood cell 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary  
66 
APPENDIX 4.    STUDY DRUG QUESTIONNAIRE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Patient Initials 
|  
|  
|  
| 
        Patient Study ID 
 |__|__|__| - |__ |__|__| 
 
STUDY DRUG QUESTIONNAIRE          
Protocol CAT-1004-301 
 
 
 
 
 
09Jul2018 
 
 
Patient Initials ________           Subject ID: _______ - _______          Date: _________________ 
 
 
This questionnaire should be completed by the caregiver of the patient. Please circle the answer that most 
closely reflects the patient’s opinion of the study drug. Circle only one answer per question.  
 
1. The taste and aftertaste (a taste that remains in your mouth after swallowing) of the study drug 
capsules are acceptable: 
 
 
 
 
 
2. The smell of the study drug capsules is acceptable: 
 
 
 
 
 
3. The size and shape of the study drug capsules are acceptable: 
 
1 
2 
3 
4 
5 
Strongly Agree 
Agree 
Neither Agree Nor 
Disagree 
Disagree 
Strongly Disagree 
1 
2 
3 
4 
5 
Strongly Agree 
Agree 
Neither Agree Nor 
Disagree 
Disagree 
Strongly Disagree 
1 
2 
3 
4 
5 
Strongly Agree 
Agree 
Neither Agree Nor 
Disagree 
Disagree 
Strongly Disagree 

Clinical Trial Protocol:  CAT-1004-301 
16 April 2020 
Confidential and Proprietary  
68 
APPENDIX 5.   PEDIATRIC OUTCOMES QUESTIONNAIRE (PODCI) 
 
 

 
 
 
Pediatric 
Outcomes Questionnaire 
 
 
 
 
Developed by: 
American Academy of Orthopaedic Surgeons® 
Pediatric Orthopaedic Society of North America 
American Academy of Pediatrics 
Shriner’s Hospitals 
 
To be completed by the parent for children 2 – 10 years old 
 
 
 
 
 
Based on the Version 2.0 Pediatrics-Parent/Child Outcomes Intrument 
 
 
Also commonly referred to as the PODCI ("Pediatric Outcomes Data Collection Instrument") 
 
 
Revised, renumbered, reformatted August 2005 
 

 
Pediatric Outcomes Instrument: Page 2 of 8 
Pediatric Health Assessment (parent-reported) 
 
FOR OFFICE USE ONLY 
 
Clinic ID  
 
 
First six letter of patient’s last name   
 
 
Physician ID 
 
 
Office Chart #  
 
 
 
Diagnosis & ICD-9 Code*  
Procedure & CPT Code 
CPT Date  
Side of body 
procedure was 
performed on:  
Primary DX  
DX  
 
ICD-9  
Tx  
 
ICD-9  
 
□ Right     □ Left  
□ Both      □ N/A  
Secondary DX  
DX  
 
ICD-9  
Tx  
 
ICD-9  
 
□ Right     □ Left  
□ Both      □ N/A  
Secondary DX  
DX  
 
ICD-9  
Tx  
 
ICD-9  
 
□ Right     □ Left  
□ Both      □ N/A  
Secondary DX  
DX  
 
ICD-9  
Tx  
 
ICD-9  
 
□ Right     □ Left  
□ Both      □ N/A  
Secondary DX  
DX  
 
ICD-9  
Tx  
 
ICD-9  
 
□ Right     □ Left  
□ Both      □ N/A  
 
 

 
Pediatric Outcomes Instrument: Page 3 of 8 
Pediatric Health Assessment (parent-reported) 
 
 
Today’s Date 
 
 / 
 
 / 
 
Thank you for completing this questionnaire!  
 
This questionnaire will help us to better understand your 
general health and any problems related to bone and muscle 
conditions.  
 
Your completion of this questionnaire is completely voluntary 
and your responses will be held in the strictest confidence.  
 
Please answer every question. Some questions may look 
like others, but each one is different.  
 
There are no right or wrong answers. If you are not sure how 
to answer a question, just give the best answer you can. You 
can make comments in the margin. We do read all your 
comments, so feel free to make as many as you wish.  
Your Child's Birth Date   
/  
 
/ 
 
Your Child's Social Security Number ___________________ 
Your Social Security Number ______________________ 
 

 
Pediatric Outcomes Instrument: Page 4 of 8 
Pediatric Health Assessment (parent-reported) 
 
 
Some kind of problems can make it hard to do many activities, such as eating, bathing, school work, and playing 
with friends. We would like to find out how your child is doing. (Circle one response on each line.)  
 
During the last week was it easy or hard for your child to:  
 
 
 
Easy 
A little 
hard 
Very 
hard 
Can't do 
at all 
Too young for 
this activity 
1. 
Lift heavy books? 
1 
2 
3 
4 
5 
2. 
Pour a half gallon of milk? 
1 
2 
3 
4 
5 
3. 
Open a jar that has been opened 
before? 
1 
2 
3 
4 
5 
4. 
Use a fork and spoon? 
1 
2 
3 
4 
5 
5. 
Comb his/her hair?  
1 
2 
3 
4 
5 
6. 
Button buttons?  
1 
2 
3 
4 
5 
7. 
Put on his/her coat? 
1 
2 
3 
4 
5 
8. 
Write with a pencil? 
1 
2 
3 
4 
5 
 
 
9.  On average, over the last 12 months, how often did your child miss school (preschool, day care, camp, etc.) 
because of his/her health?  
 
1. Rarely 
2. Once a month 
3. Two or three times a month 
4. Once a week 
5. More than once a week 
6. Does not attend school, etc. 
 
During the last week  how happy has your child been with: (Circle one response on each line.)  
 
 
 
Very 
happy 
Somewhat 
happy 
Not sure 
Somewhat 
unhappy 
Very 
unhappy 
Child is 
too young 
10. 
How he/she looks? 
1 
2 
3 
4 
5 
6 
11. 
His/her body? 
1 
2 
3 
4 
5 
6 
12. 
What clothes or shoes he/she can 
wear? 
1 
2 
3 
4 
5 
6 
13. 
His/her ability to do the same things 
his/her friends do? 
1 
2 
3 
4 
5 
6 
14. 
His/her health in general? 
1 
2 
3 
4 
5 
6 
 

 
Pediatric Outcomes Instrument: Page 5 of 8 
Pediatric Health Assessment (parent-reported) 
During the last week, how much of the time: 
(Circle one response on each line.) 
 
 
 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of the 
time 
15. 
Did your child feel sick and tired? 
1 
2 
3 
4 
16. 
Were your child full of pep and energy?  
1 
2 
3 
4 
17. 
Did pain or discomfort interfere with your 
child's activities? 
1 
2 
3 
4 
 
 
During the last week, has it been easy or hard for your child to:  
 
 
 
 
(Circle one response on each line.)  
 
 
 
 
 
 
Easy 
A little hard 
Very hard 
Can't do 
at all 
Too young for 
this activity 
18. 
Run short distances? 
1 
2 
3 
4 
5 
19. 
Bicycle or tricycle? 
1 
2 
3 
4 
5 
20. 
Climb three flights of stairs?  
1 
2 
3 
4 
5 
21. 
Climb one flight of stairs? 
1 
2 
3 
4 
5 
22. 
Walk more than a mile? 
1 
2 
3 
4 
5 
23. 
Walk three blocks? 
1 
2 
3 
4 
5 
24. 
Walk one block? 
1 
2 
3 
4 
5 
25. 
Get on and off a bus? 
1 
2 
3 
4 
5 
 
 
26.  How often does your child need help from another person for walking and climbing? (Circle one response.)  
 
1    Never 
2    Sometimes 
3    About half the time 
4    Often 
 5    All the time 
 
 
27.  How often does your child use assistive devices (such as braces, crutches, or wheelchair) for walking and 
climbing? (Circle one response.)  
 
1    Never 
2    Sometimes 
3    About half the time 
4    Often 
 5    All the time 
 
 
During the last week, has it been easy or hard for your child to: 
(Circle one response on each line.)   
 
 
Easy 
A little hard 
Very hard 
Can't do 
at all 
Too young for 
this activity 
28. 
Stand while washing his/her hands and face 
at a sink? 
1 
2 
3 
4 
5 
29. 
Sit in a regular chair without holding on? 
1 
2 
3 
4 
5 
30. 
Get on and off a toilet or chair? 
1 
2 
3 
4 
5 
31. 
Get in and out of bed? 
1 
2 
3 
4 
5 
32. 
Turn door knobs? 
1 
2 
3 
4 
5 
33. 
Bend over from a standing position and pick 
up something off the floor? 
1 
2 
3 
4 
5 

 
Pediatric Outcomes Instrument: Page 6 of 8 
Pediatric Health Assessment (parent-reported) 
 
34. How often does your child need help from another person for sitting and standing? (Circle one response.)  
 
1    Never 
2    Sometimes 
3    About half the time 
4    Often 
 5    All the time 
 
 
35. How often does your child use assistive devices (such as braces, crutches, or wheelchair) for sitting and 
standing? (Circle one response.) 
 
1    Never 
2    Sometimes 
3    About half the time 
4    Often 
 5    All the time 
 
 
36. Can your child participate in recreational outdoor activities with other children the same age?  
(For example: bicycling, tricycling, skating, hiking, jogging)  (Circle one response.)  
 
1    Yes, easily 
2    Yes, but a little hard 
3    Yes, but very hard 
4    No 
 
If you answered “no” to Question 36 above, was your child's activity limited by: (Circle yes to all that apply)  
 
 
 
Yes 
37. Pain? 
1 
38. General Health? 
1 
39. Doctor or parent instructions? 
1 
40. Fear the other kids won’t like him/her? 
1 
41. Dislike of recreational outdoor activities? 
1 
42. Too young? 
1 
43. Activity not in season? 
1 
 
 
44. Can your child participate in pickup games or sports with other children the same age?  
(For example: tag, dodge ball, basketball, soccer, catch, jump rope, touch football, hop scotch)   
(Circle one response.)  
 
1    Yes, easily 
2    Yes, but a little hard 
3    Yes, but very hard 
4    No 
 
If you answered “no” to Question 44 above, was your child's activity limited by: (Circle yes to all that apply)  
 
 
 
Yes 
45  Pain? 
1 
46. General Health? 
1 
47. Doctor or parent instructions? 
1 
48. Fear the other kids won’t like him/her? 
1 
49. Dislike of pickup games or sports? 
1 
50. Too young? 
1 
51. Activity not in season? 
1 
 
 

 
Pediatric Outcomes Instrument: Page 7 of 8 
Pediatric Health Assessment (parent-reported) 
52.  Can your child participate in competitive level sports with other children the same age? 
(For example: hockey, basketball, soccer, football, baseball, swimming, running [track or cross country], 
gymnastics, or dance) (Circle one response.)  
 
1    Yes, easily 
2    Yes, but a little hard 
3    Yes, but very hard 
4    No 
 
If you answered “no” to Question 52 above, was your child's activity limited by: (Circle yes to all that apply)  
 
 
 
Yes 
53. Pain? 
1 
54. General Health? 
1 
55. Doctor or parent instructions? 
1 
56. Fear the other kids won’t like him/her? 
1 
57. Dislike of pickup games or sports? 
1 
58. Too young? 
1 
59. Activity not in season? 
1 
 
 
60. How often in the last week did your child get together and do things with friends? (Circle one response.)  
 
1    Often 
2    Sometimes 
3    Never or rarely 
 
If you answered “sometimes” or “never or rarely” to Question 60 above, was your child's activity limited by: 
(Circle yes to all that apply)  
 
 
Yes 
61. Pain? 
1 
62. General Health? 
1 
63. Doctor or parent instructions? 
1 
64. Fear the other kids won’t like him/her? 
1 
65. Friends not around? 
1 
 
 
66. How often in the last week did your child participate in gym/recess? (Circle one response.)  
 
1    Often 
2    Sometimes 
3    Never or rarely 
4    No gym or recess 
 
If you answered “sometimes” or “never or rarely” to Question 63 above, was your child's activity limited by: 
(Circle yes to all that apply)  
 
 
Yes 
67. Pain? 
1 
68. General Health? 
1 
69. Doctor or parent instructions? 
1 
70. Fear the other kids won’t like him/her? 
1 
71. Dislike of gym/recess? 
1 
72. School not in session? 
1 
73. Does not attend school? 
1 
 
74.  Is it easy or hard for your child to make friends with children his/her own age? (Circle one response.)  
 
1  Usually easy 
2    Sometimes easy 
3    Sometimes hard 
4    Usually hard 

 
Pediatric Outcomes Instrument: Page 8 of 8 
Pediatric Health Assessment (parent-reported) 
75. How much pain has your child had during the last week? (Circle one response.)  
 
1  None 
2    Very mild 
3   Mild 
4   Moderate 
5   Severe 
6   Very severe 
 
 
76. During the last week, how much did pain interfere with your child's normal activities  (including at home, 
outside of the home, and at school)?  (Circle one response.)  
 
1    Not at all 
2    A little bit 
3    Moderately 
4    Quite a bit 
 5    Extremely 
 
 
 
What expectations do you have for your child's treatment? 
As a result of my child's treatment, I expect my child: 
(Circle one response on each line.) 
 
 
 
Definitely 
yes 
Probably 
yes 
Not sure 
Probably 
not 
Definitely 
not 
77. 
To have pain relief. 
1 
2 
3 
4 
5 
78. 
To look better. 
1 
2 
3 
4 
5 
79. 
To feel better about himself/herself. 
1 
2 
3 
4 
5 
80. 
To sleep more comfortably. 
1 
2 
3 
4 
5 
81. 
To be able to do activities at home. 
1 
2 
3 
4 
5 
82. 
To be able to do more at school. 
1 
2 
3 
4 
5 
83. 
To be able to do more play or 
recreational activities (biking, walking, 
doing things with friends).  
1 
2 
3 
4 
5 
84. 
To be able to do more sports. 
1 
2 
3 
4 
5 
85. 
To be free from pain or disability as an 
adult.  
1 
2 
3 
4 
5 
 
 
86.  If your child had to spend the rest of his/her life with his/her bone and muscle condition as it is right now, 
how would you feel about it? (Circle one response.)  
 
1    Very satisfied 
2    Somewhat satisfied 
3    Neutral  
4    Somewhat dissatisfied 
 5    Very dissatisfied 
 

Clinical Trial Protocol CAT-1004-301 
Summary of Changes 
 
 
 
 
 
 
           16 April 2020  
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 
Study of Edasalonexent in Pediatric Patients with Duchenne 
Muscular Dystrophy 
Protocol Number: 
CAT-1004-301 
Original Version Date: 
09 July 2018 
Amendment: 
 1 
Summary and Rationale for Changes 
The following information summarizes the changes captured in Amendment 1 reflective of 
study conduct during the COVID-19 pandemic:  
• 
As patients may not be able to come on-site for visits or for a reduced amount of time, 
modifications have been made to the original study procedures and schedule of 
assessments to reduce the patient’s risk or exposure to COVID-19 for Week 39 and 
Week 52 study visits. These include: 
o Allowance for the Week 52 visit to be conducted out of the visit window (but 
in no case should the projected target date be changed by more than 2 months). 
o Ability to perform study procedures either on site or remotely by using 
alternative approaches to collect study assessments. 
o As the top priority is safety, assessing for AE and concomitant medications is 
the highest priority to continue, which will occur remotely at intervals. 
o Based on the safety profile of edasalonexent to date, and consideration that all 
patients in this study have been on study drug for 6 months, other safety 
assessments, including physical examinations, chemistry and hematology labs 
and urinalysis can be deferred for six-month intervals if not feasible. 
o Drug dispensation can take place according to local site procedures, including 
secured, temperature-controlled shipments to the patients’ homes 
o A prioritized list of assessments has been included in Appendix 2 of the 
protocol. 
 
• 
Clarification that post the COVID-19 pandemic, clinical monitoring may resume with 
more intense pace to clean all data accumulated.