A 24-month Phase II Open-label, Multicenter Long-term Extension Study to Assess the Long-Term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Sponsor: ReveraGen BioPharma, Inc.

 
 
 
 
Page 1 of 184 
ReveraGen BioPharma, Inc. – CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
Amendment #1 
 
Document Title: 
Amendment #1 for a 24-month Phase II Open-label, 
Multicenter Long-term Extension Study to Assess the 
Long-term Safety and Efficacy of Vamorolone in Boys with 
Duchenne Muscular Dystrophy (DMD) 
 
Protocol Number:  
VBP15-LTE 
Document Number: 
VBP15-LTE-A1 
 
FDA IND No.: 
 
118,942 
 
Investigational Product:  
Vamorolone (VBP15) 
 
 
Sponsor: 
 
ReveraGen BioPharma, Inc. 
 
155 Gibbs Street 
Suite 433 
Rockville, MD. 20850 
 
Study Chair:  
 
Paula R. Clemens, M.D. 
 
 
 
 
Phone: (412) 383-7207 
 
 
 
 
Email: clempr@upmc.edu 
 
Medical Monitor: 
 
Benjamin D. Schwartz, M.D., Ph.D. 
 
 
Phone: (314) 220-7067 
 
 
Email: bdschw@camdengroup.com 
 
 
Document Date: 
 
03 October 2018 
 
 
This document represents proprietary information belonging to ReveraGen BioPharma, Inc.  
Unauthorized reproduction of the whole or part of the document by any means is strictly prohibited.  
This protocol is provided to you as a Principal Investigator, potential Investigator or consultant for 
review by you, your staff and Institutional Review Board or Independent Ethics Committee.  The 
information contained in this document is privileged and confidential and, except to the extent 
necessary to obtain informed consent, must not be disclosed unless such disclosure is required by 
federal or state law or regulations.  Persons to whom the information is disclosed in confidence must be 
informed that the information is confidential and must not be disclosed by them to a third party. 

4 October 2018

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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ReveraGen BioPharma, Inc. – CONFIDENTIAL 
INVESTIGATOR PROTOCOL AGREEMENT 
________________________________________________________________________ 
Amendment #1 for a 24-month Phase II Open-label, Multicenter Long-term 
Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys 
with Duchenne Muscular Dystrophy (DMD) 
Protocol Number:   
VBP15-LTE 
Document Number:   
VBP15-LTE-A1 
Sponsor: 
ReveraGen BioPharma, Inc. 
Document Date: 
03 October 2018 
____________________________________________________________________________________________________________ 
 
By my signature, I confirm that my staff and I have carefully read and understand this 
protocol, protocol amendment, amended protocol, or revised protocol and agree to 
comply with the conduct and terms of the study specified herein and with any other 
study conduct procedures provided by ReveraGen BioPharma, Inc.  
I agree to conduct the study according to this protocol and the obligations and 
requirements of clinical Investigators and all other requirements listed in 21 CFR part 
312 and all applicable local, state, and federal regulations and ICH guidelines.  I will 
not initiate this study without the approval of an Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC). 
I understand that, should the decision be made by ReveraGen BioPharma, Inc. to 
terminate prematurely or suspend the study at any time for whatever reason, such 
decision will be communicated to me in writing.  Conversely, should I decide to 
withdraw from execution of the study, I will communicate immediately such decision in 
writing to ReveraGen BioPharma, Inc. 
For protocol amendments and amended protocols, I agree not to implement the 
amendment without agreement from ReveraGen BioPharma, Inc. and prior 
submission to and written approval (where required) from the IRB/IEC, except when 
necessary to eliminate an immediate hazard to the subjects, or for administrative 
aspects of the study (where permitted by all applicable regulatory requirements). 
 
 
___________________________________________ 
__________________  
Investigator’s Signature  
 
 
 
 
Date  
 
___________________________________________  
Investigator’s Name (Please print)  
Address (Please print): 
 
RETAIN THE ORIGINAL SIGNED AGREEMENT AT YOUR SITE AND RETURN AN 
ELECTRONIC SIGNED COPYTO REVERAGEN BIOPHARMA, INC. OR DESIGNEE 

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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ReveraGen BioPharma, Inc. – CONFIDENTIAL 
SERIOUS ADVERSE EVENT CONTACT INFORMATION 
In the event of a serious adverse event (SAE) (see Section 7.2.6.1), the Investigator 
will complete the SAE electronic case report form within 24 hours of first awareness 
of the event.  In the unlikely event that the electronic study database is inaccessible 
and the Investigator is unable to complete the SAE electronic case report form 
within 24 hours, the SAE Notification Form (pdf) should be completed and emailed 
or printed/faxed to the PRA safety management team within 24 hours, using the 
contact information below: 
Email CHOSafety@prahs.com 
Drug Safety Fax: 1-888-772-6919 or 1-434-951-3482 
 
SAE Questions: Drug Safety Hotline: 1-800-772-2215 or 1-434-951-3489 
 

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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ReveraGen BioPharma, Inc. – CONFIDENTIAL 
PROTOCOL AMENDMENT TRACKING 
Document 
Document Number 
Approval Date 
Original Protocol 
VBP15-LTE 
11 January 2017 
Amendment #1 
VBP15-LTE-A1 
03 October 2018 
Reasons for Protocol Amendment #1: 
1. To update Section 1 Introduction with safety results from Phase II studies in DMD boys 
(VBP15-002 and VBP15-003); 
2. To update Section 1.5 Overall Benefit/Risk; 
3. To update Section 13 References; 
4. To clarify that dose may be escalated incrementally to 6.0 mg/kg/day; 
5. To clarify the circumstances under which study drug dose should be interrupted, 
de-escalated, or discontinued; 
6. To allow dose de-escalation from 6.0 mg/kg/day to 2.0 mg/kg/day to be followed by dose 
escalation to 4.0 mg/kg/day, balancing efficacy and safety concerns, in the opinion of the 
Investigator; 
7. To prohibit use of Exondys 51, Translarna, and other medications indicated for treatment of 
DMD during the study; 
8. To add details of Data and Safety Monitoring Board (DSMB) responsibilities; 
9. To add collection of 8.5 mL of blood at the Month 24 Visit for deoxyribonucleic acid 
(DNA) testing for established genetic modifiers of DMD; 
10. To add spine x-ray for detection of fracture at the Month 24 Visit; 
11. To add hand x-ray for assessment of bone age at the Month 24 Visit; 
12. To remove the designation of BMI z-score as the primary safety outcome;  
13. To update the primary efficacy endpoint; 
14. To remove comparison of vamorolone with prednisone-treated historical control data for 
serum PD biomarkers of safety; 
15. To add comparison of vamorolone to prednisone- and deflazacort-treated historical control 
data for bone age, spine fracture, and height z-score, and comparison to deflazacort-treated 
historical control data for BMI z-score;  
16. To update the statistical methodology and composition of the control populations; 
17. To clarify that collection of the Pediatric Outcomes Data Collection Instrument (PODCI) 
does not need to be repeated at the VBP15-LTE Baseline Visit if the Baseline Visit occurs 
≤ 28 days after the date of the VBP15-003 Week 24 Visit;  
18. To clarify the PD biomarkers to be evaluated; 
19. To remove the designation of methodologies to be used for measurement of exploratory PD 
biomarkers; 
20. To clarify the exploratory endpoint for PODCI assessment;  
21. To clarify that vital signs, height, and clinical laboratory test results are included in safety 
data; and 
22. To correct typographical errors. 
The Sections changed by amendment are listed in was/is format in Appendix 14.2. 

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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ReveraGen BioPharma, Inc. – CONFIDENTIAL 
STUDY SYNOPSIS 
Protocol Title 
A 24-month Phase II Open-label, Multicenter, Long-Term Extension Study to 
Assess the Long-term Safety and Efficacy of Vamorolone in Boys with 
Duchenne Muscular Dystrophy (DMD) 
Protocol Number 
VBP15-LTE 
Name of Sponsor 
ReveraGen BioPharma, Inc. 
Drug Substance 
delta-1,4,9(11)-pregnatriene-17-alpha,21-dihydroxy-16-alpha-methyl-3,20-
dione 
Investigational Drug 
Product 
Vamorolone, 4% suspension for oral dosing 
Phase of 
Development 
Phase II 
Indication 
Treatment of Duchenne muscular dystrophy (DMD) 
Objectives 
Primary: 
1. To evaluate the long-term safety and tolerability of vamorolone, 
administered orally at daily doses up to 6.0 mg/kg over a 24-month 
Treatment Period, in young boys with DMD who completed protocol 
VBP15-003; and 
2. To compare the efficacy, as measured by the Time to Stand Test 
(TTSTAND), of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period vs. untreated DMD historical 
controls in young boys with DMD. 
Secondary: 
1. To investigate the effects of vamorolone, administered orally at daily doses 
up to 6.0 mg/kg over a 24-month Treatment Period on serum 
pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal 
axis suppression, and bone turnover);  
2. To investigate the effects of vamorolone, administered orally at daily doses 
up to 6.0 mg/kg over a 24-month Treatment Period, on muscle strength, 
mobility and functional exercise capacity vs. untreated DMD historical 
controls as measured by Time to Run/Walk Test (TTRW), North Star 
Ambulatory Assessment (NSAA), Time to Climb Test (TTCLIMB), 
6-minute Walk Test (6MWT), and Quantitative Muscle Testing (QMT) in 
young boys with DMD; and 
3. To compare the safety, as assessed by bone age, spine fractures, BMI 
z-score, and height z-score, of vamorolone administered orally at daily 
doses up to 6.0 mg/kg over a 24-month Treatment Period vs. prednisone- 
and deflazacort-treated historical control boys with DMD. 
Exploratory: 
1. To investigate the effects of vamorolone administered orally at daily doses 
up to 6.0 mg/kg over a 24-month Treatment Period on Quality of Life 
measures (Pediatric Outcomes Data Collection Instrument [PODCI]);  
2. To investigate the effects of vamorolone administered orally at daily doses 
up to 6.0 mg/kg over a 24-month Treatment Period on additional 
exploratory PD biomarkers; and 

Vamorolone 
03 October 2018 
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Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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ReveraGen BioPharma, Inc. – CONFIDENTIAL 
3. To determine if established genetic modifiers of DMD (gene 
polymorphisms associated with disease severity, or response to 
glucocorticoid treatment) are similarly associated with vamorolone-treated 
DMD patients (baseline disease severity, or response to vamorolone 
treatment). 
Study Design 
This long-term extension (LTE) study is an open-label, multicenter study to 
evaluate the long-term safety, tolerability, clinical efficacy, and PD of 
vamorolone at dose levels up to 6.0 mg/kg administered daily by liquid oral 
suspension over a Treatment Period of 24 months to young boys with DMD.   
Subjects who have completed the Phase IIa extension VBP15-003 Study 
Week 24 Follow-up assessments prior to enrollment are eligible for enrollment 
into the VBP15-LTE study.   
The LTE study is comprised of a Pretreatment Baseline Period of up to 
24 hours, which begins with the signing of the VBP15-LTE-specific informed 
consent form (ICF), a 24-month Treatment Period, and an up to 5-week 
Dose-tapering Period for subjects who elect to transition off vamorolone 
treatment at the end of the study. 
Subjects are enrolled at the time of the Informed Consent Form (ICF) signing.  
Parents or guardians of eligible subjects will provide written informed consent 
for VBP15-LTE long-term extension study participation.  The assessments 
collected at the final VBP15-003 Week 24 Visit will serve as the Baseline 
assessments for the VBP15-LTE study.  
Planned Sample 
Size 
Up to approximately 50 subjects who complete the VBP15-003 study will be 
enrolled. 
Population 
Inclusion Criteria: 
1. Subject’s parent or legal guardian has provided written informed consent 
and HIPAA authorization (if applicable) prior to any VBP15-LTE long-
term extension study-specific procedures; 
2. Subject has previously completed study VBP15-003 up to and including 
the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study 
at the conclusion of the VBP15-003 Week 24 Visit [Note: if entering the 
dose-tapering period, subject is enrolling within 8 weeks after the 
VBP15-003 final visit following dose-tapering]; and 
3. Subject and parent/guardian are willing and able to comply with scheduled 
visits, study drug administration plan, and study procedures. 
Exclusion Criteria: 
1. Subject had a serious or severe adverse event in study VBP15-003 that, in 
the opinion of the Investigator, was probably or definitely related to 
vamorolone use and precludes safe use of vamorolone for the subject in 
this long-term extension study; 
2. Subject has current or history of major renal or hepatic impairment, 
diabetes mellitus or immunosuppression;  
3. Subject has current or history of chronic systemic fungal or viral infections; 
4. Subject has used mineralocorticoid receptor agents, such as spironolactone, 
eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate 
potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the 
first dose of study medication; 
5. Subject has evidence of symptomatic cardiomyopathy.  [Note: 
Asymptomatic cardiac abnormality on investigation would not be 
exclusionary]; 

Vamorolone 
03 October 2018 
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Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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6. Subject is currently being treated or has received previous treatment with 
oral glucocorticoids or other immunosuppressive agents [Notes: Past 
transient use of oral glucocorticoids or other oral immunosuppressive 
agents for no longer than 3 months cumulative, with last use at least 3 
months prior to first dose of study medication, will be considered for 
eligibility on a case-by-case basis.  Inhaled and/or topical glucocorticoids 
prescribed for an indication other than DMD are permitted but must be 
administered at stable dose for at least 3 months prior to study drug 
administration]; 
7. Subject has used idebenone within 4 weeks prior to the first dose of study 
medication; 
8. Subject has an allergy or hypersensitivity to the study medication or to any 
of its constituents;  
9. Subject has severe behavioral or cognitive problems that preclude 
participation in the study, in the opinion of the Investigator; 
10. Subject has previous or ongoing medical condition, medical history, 
physical findings or laboratory abnormalities that could affect safety, make 
it unlikely that treatment and follow-up will be correctly completed or 
impair the assessment of study results, in the opinion of the Investigator 
11. Subject is currently taking any investigational drug, or has taken any 
investigational drug other than vamorolone within 3 months prior to the 
start of study treatment. 
 Note: Subjects may be re-evaluated if ineligible due to a transient condition 
which would prevent the subject from participating. 
Number of Centers 
The study will be conducted at approximately 15 United States (US) and 
non-US study sites. 
Study Period 
First subject enrolled: 1Q 2017 
Last subject last visit: 2Q 2020 
Study Duration  
Up to approximately 4 years total duration 
Individual Subject 
Study Duration 
Approximately 24-25 months: 
• 
Baseline Period: up to 24 hours immediately prior to administration of 
first dose of study medication in VBP15-LTE long-term extension study 
• 
Treatment Period: 24 months 
• 
Dose-tapering Period: up to 5 weeks 
• 
Subjects may leave the study at their own discretion at any time.  Subjects 
who discontinue vamorolone will follow the Dose-tapering Period 
procedures. 
Study Drug 
Formulation, 
Dosage & 
Administration 
Vamorolone 4% oral suspension will be administered once daily over a 
24-month Treatment Period, at one of the following planned dose levels 
investigated in VBP15-003: 0.25 mg/kg/day, 0.75 mg/kg/day, 2.0 mg/kg/day, or 
6.0 mg/kg/day with a glass of full fat milk (approximately 8 grams fat or 
equivalent).   
Subjects will receive vamorolone throughout the 24-month Treatment Period, 
initially at the same dose level they received at the time they completed the 
Week 24 Final Visit of the VBP15-003 Phase IIa extension study.  Subjects, 
after they have been on their initial dose for at least 1 month in VBP15-LTE 
may be escalated to the next higher dose level at the discretion of the Study 
Chair and Medical Monitor once the next higher dose has been determined to be 
safe in the VBP15-002 Phase IIa Study, and no safety issues with that dose have 

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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emerged in the VBP15-003 Phase IIa extension study.  (See procedure detailed 
below on how to escalate to the next dose level).   
Dosing is to occur at home throughout the 24-month Treatment Period, except 
at the Month 9 and Month 21 Visits when dosing will occur at the study site to 
accommodate morning fasted blood collections.  Study drug will be 
administered by mouth using a volumetric syringe.  Following administration of 
the dose of study drug, the syringe will be filled once with water and the water 
will be administered by mouth using the volumetric syringe.  The subject will 
then drink approximately 50 mL (approximately 2 ounces) of water to ensure 
the full dose has been ingested. 
The daily dose of study medication should be taken with a glass of full fat milk 
(approximately 8 grams of fat) or food with similar fat content of the subject’s 
choice.  There are no additional food or drink restrictions before or after dosing. 
Procedure to escalate to the next higher dose: Dose escalation within this 
study will be considered at the discretion of the Study Director and Medical 
Monitor.  Subjects, after they have been on their initial dose for at least 1 month 
in VBP15-LTE, may be escalated to the next higher dose level once the next 
higher dose has been determined to be safe in the VBP15-002 Phase IIa Study, 
and no safety issues with that dose have emerged in the VBP15-003 Phase IIa 
extension study.  Dose may be escalated in no greater than 3 increments, not to 
exceed the MTD identified in the VBP15-002 dose finding study and confirmed 
in the VBP15-003 Phase IIa extension study. 
Study Summary 
This long-term extension study is an open-label, multiple-dose study to evaluate 
the long-term safety, tolerability, efficacy and PD of vamorolone administered 
once daily by liquid oral suspension over a Treatment Period of 24 months to 
young boys with DMD who participated in the VBP15-002 Phase IIa and 
VBP15-003 Phase IIa extension core studies. 
Only subjects who have completed the VBP15-003 Phase IIa extension study 
Week 24 Final Visit assessments will be eligible for participation in this 
open-label VBP15-LTE study.  Participation in this LTE study will be 
discussed with the subject’s parent or guardian prior to the VBP15-003 Week 
24 Visit.  Standard of care treatment (glucocorticoids) for DMD should be 
discussed with the subject’s parent/guardian prior to the decision to enroll the 
subject in the LTE study.  Standard of care glucocorticoids should be offered to 
the subject following completion of the VBP15-003 Phase IIa extension study, 
if the subject’s parent or guardian does not wish to enroll the subject in this 
long-term extension study and/or the Investigator feels it to be in the best 
interest of the subject.  A total of up to approximately 50 subjects will be 
enrolled into this long-term extension study. 
The parents or legal guardians of subjects who choose to enroll in this 
long-term extension study will give written informed consent for the long-term 
extension study at the VBP15-LTE Baseline Day -1 Visit, which may coincide 
with the conclusion of the VBP15-003 Week 24 Visit following all assessments 
in the trial, or may occur up to 8 weeks following the final visit of the Dose-
tapering Period for subjects who dose-taper.  Subjects are considered to be 
enrolled in the VBP15-LTE long-term extension study after the parent or 
guardian has signed the VBP15-LTE-specific ICF at the Baseline Visit.  Each 
subject will retain the study identification number assigned to him at the start of 
the Phase IIa core study VBP15-002 and used for the Phase IIa extension study 
VBP15-003. 
Subjects who participated in the VBP15-003 study will begin dosing in this 
study on Study Day 1 at the same vamorolone dose level they received at the 
time of the Week 24 Final Visit in the VBP15-003 Phase IIa extension study.  

Vamorolone 
03 October 2018 
Amendment #1  
Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
IND 118,942 
 
 
 
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Subjects, after they have been on their initial dose for at least 1 month in 
VBP15-LTE, may be escalated to the next higher dose level at the discretion of 
the Study Chair and Medical Monitor once the next higher dose has been 
determined to be safe in the VBP15-002 Phase IIa Study, and no safety issues 
with that dose have emerged in the VBP15-003 Phase IIa extension study. 
The planned dose levels in the VBP15-003 study are 0.25 mg /kg (Dose 
Level 1), 0.75 mg/kg (Dose Level 2), 2.0 mg/kg (Dose Level 3), and 6.0 mg/kg 
(Dose Level 4). 
If dose limiting toxicities are identified in the VBP15-002 or VBP15-003 
studies which preclude confirmation of safety of planned dose levels, the dose 
levels in this long-term extension study will be modified, as needed. 
In the event any clinical observation suggests an intolerability for an individual 
subject to the study medication, in the opinion of the Investigator, the subject’s 
dose level may be decreased to the next lower dose level and maintained at that 
lower dose level throughout the duration of the Treatment Period, with the 
caveat stated below for subjects de-escalating from 6.0 mg/kg/day to 2.0 
mg/kg/day.  In the event the next lower dose level is also not tolerated and is 
considered a safety risk to the subject, in the opinion of the Investigator, Study 
Chair, and Medical Monitor, the subject will be withdrawn from the study.  
Subjects whose dose is decreased from 6.0 mg/kg/day to 2.0 mg/kg/day may 
have their dose subsequently increased to 4.0 mg/kg/day if they have been 
taking the 2.0 mg/kg/day dose for at least one month and, in the opinion of the 
Investigator, balancing efficacy with safety concerns, they could benefit from 
an intermediate higher dose.   
Subjects will be assessed for safety and tolerability, clinical efficacy, 
pharmacodynamic biomarkers, and quality of life at scheduled visits throughout 
the 24-month Treatment Period.  Treatment Period study visits for VBP15-LTE 
will occur at Month 1, Month 3 and then at 3-month intervals extending through 
Month 24.  Adverse events (AEs), including serious adverse events (SAEs), and 
concomitant medications will be recorded throughout the study. 
Once-daily Treatment Period study drug dosing will occur at home on all days 
throughout the 24-month Treatment Period, except at the Month 9 and Month 
21 Visits when dosing will occur at the study site to accommodate morning 
fasted blood collections.   
Subject diaries will be dispensed at Baseline Day -1 and at each 3-monthly 
study visit to record AEs and any changes to concomitant medications taken 
during the study. 
All subjects will return to the clinical site for Month 24 assessments.  Following 
completion of the 24-month Treatment Period, subjects may be offered further 
extended treatment with vamorolone in a separate extension study, or switch to 
standard of care treatment (e.g., glucocorticoids) for DMD, as deemed 
appropriate for each subject.  Alternatively, subjects may choose to discontinue 
vamorolone and not begin standard of care glucocorticoid treatment for DMD.  
Subjects who switch to standard of care glucocorticoids for DMD or who 
discontinue treatment will participate in a Dose-tapering Period of up to 5 
weeks in duration, following the end of the Treatment Period and prior to 
discharge from the study; subjects who elect to receive further vamorolone 
treatment will be discharged from the VBP-LTE study after completion of final 
VBP-LTE study assessments at the Month 24 Visit, prior to enrollment in the 
separate extension study.  Subjects will be discharged from the study following 
completion of all final Month 24 or Dose-tapering Period assessments, as 
appropriate. 

Vamorolone 
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Document No. VBP15-LTE-A1 
Protocol No. VBP15-LTE 
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In the event that any clinical or laboratory parameters remain abnormal at the 
time of discharge from the study, the subject will be followed medically as 
clinically indicated. 
A subject may decide to discontinue vamorolone treatment at any time.  If the 
subject discontinues vamorolone, then the up-to-5-week dose-tapering schedule 
should be followed. 
Safety Measures 
• 
Physical examination 
• 
Weight  
• 
Height 
• 
Body Mass Index (BMI) 
• 
Vital signs (supine blood pressure, heart rate, respiratory rate, oral 
temperature) 
• 
Clinical laboratory tests  
o Hematology and biochemistry  
o Urinalysis (by dipstick and microscopic analysis) 
o Lipid profile (triglycerides, total cholesterol, low density lipoprotein 
[LDL], high density lipoprotein [HDL]) 
• 
12-lead electrocardiogram (ECG) 
• 
Hand x-ray 
• 
Spine x-ray 
• 
Clinical signs and symptoms (AEs and SAEs) 
• 
Grading of clinical and clinical laboratory AEs will be according to the 
Common Terminology Criteria for Adverse Events (CTCAE), v4.0.3  
Pharmacodynamic 
Measures 
• 
Blood will be drawn for a serum PD biomarker panel at scheduled visits 
during the Treatment Period and at the end of the Dose-tapering Period, if 
applicable, to explore the effect of vamorolone on biomarkers of adrenal 
axis suppression, bone turnover, insulin resistance, and exploratory 
biomarkers of efficacy and safety. 
Clinical Efficacy 
Measures 
• 
Time to Stand Test (TTSTAND) 
• 
Time to Climb Test (TTCLIMB) 
• 
Time to Run/Walk Test (TTRW) 
• 
North Star Ambulatory Assessment (NSAA) 
• 
Six-minute Walk Test (6MWT) 
• 
Quantitative Muscle Testing (QMT) 
Exploratory 
Measures  
• 
Measures of serum PD biomarkers 
• 
Quality of life (PODCI) 
• 
DNA testing for established genetic modifiers of DMD 
Statistical Methods 
Analysis Populations: 
Four populations will be defined for data analysis: the Safety Population, the 
Full Analysis Set, the control population CINRG Duchenne Natural History 
Study, and the control population FOR DMD Study. 
Safety Population 
All subjects who receive at least one dose of vamorolone study medication in 
the VBP15-LTE extension study will be included in the Safety Population.  The 
Safety Population is the primary analysis population for safety assessments.  
This is also the modified Intention to Treat (mITT) population. 
Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in 
the VBP15-LTE extension study and have at least one post-baseline assessment 
will be included in the FAS.  The FAS is the primary analysis population for 
clinical efficacy and PD assessments.  The FAS population is the mITT 

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Protocol No. VBP15-LTE 
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population, with the additional requirement of having at least one post-baseline 
assessment.  Subjects who receive at least one dose of vamorolone but never 
have post-baseline assessments will be excluded. 
Control Population from CINRG Duchenne Natural History Study  
The control population from the CINRG Duchenne Natural History Study will 
include all subjects who were observed as part of the study in ages ≥ 4 years 
and <7 years of age at a start of an interval of observation; observed for at least 
two years with TTSTAND, TTCLIMB, TTRW, NSAA, 6MWT and QMT 
measured; remained glucocorticoid-naive during the entire observation period; 
and were able to walk independently without assistive devices, able to complete 
the TTSTAND; and lacked any history of disease, impairment, or medications 
that would have made them ineligible to receive the vamorolone intervention as 
defined by the VBP15-LTE exclusion criteria at the start of the interval. 
Control Population FOR DMD Study 
The control population from the FOR DMD Study will include all subjects who 
were 4-7 years old at entry and who were randomized to the daily prednisone or 
daily deflazacort arm. 
General Statistical Considerations: 
All measurements will be analyzed based upon the type of distribution and 
descriptive statistics presented by treatment group and time point, as 
appropriate.  No interim statistical analyses are planned.  Missing values for 
safety and exploratory outcomes will be treated as missing. 
All statistical tests will be performed at the 0.05 level.  Paired t-tests will be 
utilized for select variables.  When available, baseline from the VBP15-002 will 
be utilized when calculating change from baseline. 
 
Efficacy Analyses: 
The primary efficacy outcome is TTSTAND (velocity).  Secondary efficacy 
outcomes are the NSAA assessment, TTCLIMB, TTRW, QMT, and the 
6MWT.  TTSTAND, TTCLIMB, and TTRW will be analyzed using raw scores 
and velocity.   
The primary outcome is TTSTAND (velocity) change from VBP15-002 study 
baseline to Month 24 and will be compared between vamorolone and historical 
untreated controls using a restricted maximum likelihood (REML)-based mixed 
model for repeated measures (MMRM).  This model will include fixed effects 
for treatment, visit, baseline TTSTAND velocity (from the VBP15-002 study), 
age at study entry, and the treatment-by-visit interaction.  The initial model will 
compare combined vamorolone doses to untreated natural history controls and 
subsequent secondary models may compare individual and other combinations 
of dose levels to untreated natural history controls.  The secondary outcome 
measures will be compared using similar models.  Full details will be provided 
in the Statistical Analysis Plan (SAP).  
Pharmacodynamics Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover will be assessed, as well as exploratory biomarkers of safety and 
efficacy.  Biomarkers will be summarized descriptively over time. 

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Safety Analyses: 
All subjects who received at least one dose of vamorolone (Safety Population) 
will be included in the safety analyses.  In general, descriptive statistics for each 
safety endpoint will be presented by the combined vamorolone dose level, 
individual dose levels, and other combinations of dose levels. 
Safety data will include BMI (raw units and z-score), height (raw units and 
z-score), vital signs, clinical laboratory test results, hand x-ray, spine x-ray, and 
ECG results.   
Changes in BMI z-score and height z-score will be analyzed using the same 
type of statistical models used for efficacy with vamorolone being compared 
with the daily prednisone and the daily deflazacort arms from the FOR DMD 
study.  Hand x-ray and spine x-ray results will also be compared with the daily 
prednisone and the daily deflazacort arms from the FOR DMD study.   
Adverse events will be summarized overall and by dose level by system organ 
class (SOC) and preferred term (using the Medical Dictionary for Regulatory 
Activities [MedDRA]); by relationship to study medication; and by intensity 
(CTCAE grade).   
 

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TABLE OF CONTENTS 
PROTOCOL AMENDMENT TRACKING....................................................................5 
STUDY SYNOPSIS ...........................................................................................................6 
LIST OF TABLES ...........................................................................................................18 
LIST OF FIGURES .........................................................................................................19 
LIST OF ABBREVIATIONS .........................................................................................20 
1 
INTRODUCTION...................................................................................................24 
1.1 
BACKGROUND AND UNMET NEED........................................................................24 
1.2 
NONCLINICAL EXPERIENCE .................................................................................26 
1.2.1 
Safety Pharmacology ................................................................................26 
1.2.2 
Pharmacokinetics and Metabolism ..........................................................28 
1.2.3 
Toxicology .................................................................................................32 
1.3 
CLINICAL EXPERIENCE ........................................................................................40 
1.3.1 
Phase I Study in Healthy Adult Volunteers .............................................40 
1.3.2 
Pharmacokinetics in Phase II Study in 4 to 7 years Duchenne 
Muscular Dystrophy Boys (VBP15-002) ..................................................55 
1.3.3 
Safety in Phase II Studies in 4 to7 years Duchenne Muscular 
Dystrophy Boys (VBP15-002 and VBP15-003)........................................57 
1.4 
RATIONALE FOR STUDY DESIGN..........................................................................59 
1.5 
OVERALL BENEFIT/RISK .....................................................................................62 
2 
STUDY OBJECTIVES AND ENDPOINTS .........................................................63 
2.1 
STUDY OBJECTIVES ..............................................................................................63 
2.1.1 
Primary Objectives ....................................................................................63 
2.1.2 
Secondary Objectives ................................................................................63 
2.1.3 
Exploratory Objectives ..............................................................................64 
2.2 
STUDY ENDPOINTS ...............................................................................................65 
2.2.1 
Safety Endpoints .......................................................................................65 
2.2.2 
Clinical Efficacy Endpoints ......................................................................66 
2.2.3 
Pharmacodynamic Endpoints...................................................................67 
2.2.4 
Exploratory Endpoints ..............................................................................67 
2.2.5 
Endpoints for Subject Reported Outcomes ..............................................67 
3 
STUDY DESIGN .....................................................................................................67 
3.1 
OVERALL STUDY DESIGN ....................................................................................67 
3.2 
STUDY SUMMARY .................................................................................................70 

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4 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS .........................70 
4.1 
SUBJECT SCREENING, ENROLLMENT, AND IDENTIFICATION LOG .....................70 
4.2 
INCLUSION CRITERIA ...........................................................................................71 
4.3 
EXCLUSION CRITERIA ..........................................................................................71 
4.4 
WITHDRAWAL OF SUBJECTS FROM STUDY .........................................................73 
4.5 
REPLACEMENT OF WITHDRAWN SUBJECTS ........................................................74 
4.6 
TERMINATION OF STUDY .....................................................................................74 
5 
TREATMENT OF STUDY SUBJECTS ..............................................................74 
5.1 
STUDY MEDICATION ADMINISTERED ..................................................................74 
5.2 
IDENTITY OF INVESTIGATIONAL PRODUCT .........................................................75 
5.3 
DOSAGE SCHEDULE AND ADMINISTRATION OF STUDY MEDICATION ................75 
5.4 
RATIONALE FOR DOSE SELECTION .....................................................................76 
5.5 
TREATMENT COMPLIANCE ..................................................................................77 
5.6 
STUDY DRUG DOSE INTERRUPTION, DE-ESCALATION, OR DISCONTINUATION .77 
5.7 
PRIOR AND CONCOMITANT MEDICATIONS AND THERAPIES ..............................78 
5.7.1 
Prior Therapy ............................................................................................78 
5.7.2 
Concomitant Therapy ...............................................................................78 
5.7.3 
Prohibited Therapies .................................................................................79 
5.7.4 
Permitted Therapies ..................................................................................80 
5.8 
STUDY MEDICATION MANAGEMENT ...................................................................80 
5.8.1 
Packaging and Labeling of Study Medication .........................................80 
5.8.2 
Storage of Study Medication.....................................................................81 
5.8.3 
Study Medication Shipping and Handling ...............................................81 
5.8.4 
Study Medication Accountability..............................................................82 
5.9 
PROCEDURES FOR ASSIGNING SUBJECT STUDY NUMBERS .................................82 
6 
STUDY SCHEDULE ..............................................................................................83 
6.1 
TIME AND EVENTS SCHEDULE .............................................................................83 
6.2 
INFORMED CONSENT/HIPAA AUTHORIZATION .................................................87 
6.3 
VISIT SCHEDULE AND PROCEDURES ....................................................................88 
6.3.1 
Baseline Period (Day -1) ...........................................................................88 
6.3.2 
Treatment Period Day 1 ............................................................................90 
6.3.3 
Treatment Period Months 1-24.................................................................91 
6.3.4 
Dose Tapering Period (Months 24-25) .....................................................92 
6.4 
SUBJECT DISCONTINUATION ................................................................................94 
6.5 
STUDY COMPLETION ............................................................................................94 
7 
STUDY ASSESSMENTS AND MEASUREMENTS ..........................................94 
7.1 
DEMOGRAPHIC ASSESSMENTS .............................................................................94 

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7.1.1 
Genetic Modifiers of DMD .......................................................................94 
7.2 
SAFETY AND TOLERABILITY ASSESSMENTS ........................................................95 
7.2.1 
Interim Medical History............................................................................95 
7.2.2 
Physical Examination, Weight, and Height .............................................95 
7.2.3 
Vital Signs .................................................................................................96 
7.2.4 
Clinical Laboratory Tests..........................................................................96 
7.2.5 
12-Lead ECG .............................................................................................99 
7.2.6 
Adverse Events and Serious Adverse Events .........................................100 
7.2.7 
Bone Age (Hand X-ray) ..........................................................................107 
7.2.8 
Spine X-ray ..............................................................................................107 
7.3 
CLINICAL EFFICACY AND PHARMACODYNAMIC ASSESSMENTS ......................108 
7.3.1 
Time to Stand Test (TTSTAND) .............................................................108 
7.3.2 
Time to Climb Test (TTCLIMB) .............................................................108 
7.3.3 
Time to Run/Walk Test (TTRW) ............................................................108 
7.3.4 
North Star Ambulatory Assessment (NSAA) .........................................109 
7.3.5 
Six-minute Walk Test (6MWT)...............................................................109 
7.3.6 
Quantitative Muscle Testing (QMT) ......................................................110 
7.3.7 
Pharmacodynamic Biomarker Panel .....................................................110 
7.3.8 
Pediatric Outcomes Data Collection Instrument (PODCI) ...................111 
7.4 
TOTAL BLOOD VOLUME REQUIRED ..................................................................112 
8 
DATA COLLECTION .........................................................................................112 
8.1 
SOURCE DOCUMENTS .........................................................................................112 
8.2 
ELECTRONIC CASE REPORT FORM COMPLETION ............................................113 
8.3 
DATA PROCESSING .............................................................................................114 
8.4 
SUBJECT DIARIES ...............................................................................................114 
9 
STATISTICAL METHODS AND PLANNED ANALYSES ............................114 
9.1 
STATISTICAL AND ANALYTICAL PLAN (SAP) ...................................................115 
9.1.1 
Deviations from the Statistical Analysis Plan ........................................115 
9.2 
ANALYSIS POPULATIONS....................................................................................115 
9.2.1 
Safety Population ....................................................................................115 
9.2.2 
Full Analysis Set (FAS) ..........................................................................116 
9.2.3 
Control Population DNHS Study ...........................................................116 
9.2.4 
Control Population FOR DMD Study ....................................................116 
9.3 
MEASURES TAKEN TO AVOID/MINIMIZE BIAS .................................................116 
9.4 
INTERIM ANALYSIS ............................................................................................116 
9.5 
MISSING, UNUSED, AND SPURIOUS DATA ..........................................................117 
9.6 
STATISTICAL ANALYSIS .....................................................................................117 

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9.6.1 
General Considerations ..........................................................................117 
9.6.2 
Subject Disposition, Demographics, and Baseline Characteristics ......117 
9.6.3 
Safety Analyses ........................................................................................117 
9.6.4 
Clinical Efficacy and Pharmacodynamic Analyses ...............................118 
9.6.5 
Concurrent Medications .........................................................................119 
10 
STUDY MANAGEMENT AND ETHICAL AND REGULATORY 
REQUIREMENTS................................................................................................119 
10.1 REGULATORY APPROVAL AND GOOD CLINICAL PRACTICE ............................119 
10.2 INVESTIGATOR RESPONSIBILITIES ....................................................................120 
10.2.1 
Subject Information and Informed Consent ..........................................120 
10.2.2 
Institutional Review Board/Independent Ethics Committee Approval 
and Other Institutional Requirements ...................................................121 
10.2.3 
Study Documentation ..............................................................................122 
10.2.4 
Delegation of Investigator Responsibilities ............................................123 
10.3 PROTOCOL DEVIATIONS AND VIOLATIONS .......................................................123 
10.3.1 
Protocol Deviation and Violation Definitions .......................................123 
10.3.2 
Reporting Deviations/Violations.............................................................124 
10.4 STUDY RECORDS RETENTION AND DIRECT ACCESS TO SOURCE DOCUMENTS124 
10.5 DATA AND SAFETY MONITORING BOARD (DSMB) AND OTHER STUDY 
MONITORING ...............................................................................................................125 
10.5.1 
DSMB ......................................................................................................125 
10.5.2 
Study Monitoring ....................................................................................126 
10.6 QUALITY ASSURANCE ........................................................................................127 
10.7 STUDY TERMINATION AND SITE CLOSURE........................................................128 
10.8 SITE TERMINATION ............................................................................................128 
10.9 DISCONTINUATION OF STUDY ............................................................................129 
11 
DISCLOSURE OF DATA ....................................................................................129 
11.1 CONFIDENTIALITY .............................................................................................129 
11.2 PUBLICATION .....................................................................................................130 
12 
INVESTIGATOR’S PROTOCOL AGREEMENT ...........................................131 
13 
REFERENCES ......................................................................................................132 
14 
APPENDICES .......................................................................................................137 
APPENDIX 14.1 VAMOROLONE DOSE CALCULATION WORKSHEET AND BULK 
DISPENSING GUIDE ......................................................................................................138 
APPENDIX 14.2 PROTOCOL AMENDMENT #1 COMPLETE LIST OF CHANGES ........141 
 

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LIST OF TABLES 
Table 1 
Summary of pharmacokinetic parameters for vamorolone after oral 
administration of single doses of 0.1, 0.3, 1.0, 3.0, 8.0, and 20.0 mg/kg to 
healthy subjects under fasted conditions .................................................42 
Table 2 
Summary of pharmacokinetic parameters for vamorolone after single 
dose oral administration of 8 mg/kg to healthy subjects under fed and 
fasted conditions .........................................................................................44 
Table 3 
Summary of pharmacokinetic parameters for vamorolone during oral 
administration of 1, 3, 9, and 20 mg/kg doses once daily for 14 days to 
healthy subjects under fasted conditions .................................................45 
Table 4 
Serum osteocalcin concentrations (ng/ml) in vamorolone Phase I MAD 
groups.  Within 2 hours prior to dosing (pre-dose); 8 hours postdose 
day 1 (8 hr); 1 day after 14 days of dosing (14 day); 3 days after last 
dose (Rec) ....................................................................................................53 
Table 5 
Serum CTX1 concentrations (ng/ml) in vamorolone Phase I MAD 
groups.  Within 2 hours prior to dosing (pre-dose); 8 hours postdose 
day 1 (8 hr); 1 day after 14 days of dosing (14 day); 3 days after last 
dose (Rec) ....................................................................................................53 
Table 6 
Pharmacokinetics of 0.25 mg/kg/day vamorolone in 4-7 years DMD 
boys ..............................................................................................................56 
Table 7 
Biomarkers previously defined to be responsive to chronic doses of 
glucocorticoids in DMD boys ....................................................................61 
Table 8 
Schedule of Study Activities ......................................................................85 
Table 9 
Vamorolone Dose Tapering .......................................................................93 
Table 10 
Hematology, Chemistry, and Lipids Clinical Laboratory Tests ............98 
Table 11 
Urinalysis Clinical Laboratory Tests ........................................................98 
Table 12 
Pharmacodynamic Biomarkers ..............................................................111 
Table 13 
Blood Sample Number and Volume .......................................................112 
 

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LIST OF FIGURES 
Figure 1 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) after oral administration of single doses of 0.1, 
0.3, 1, 3, 8, and 20 mg/kg to healthy subjects under fasted conditions - 
linear plot (top); semi-logarithmic plot (bottom) ....................................41 
Figure 2 
Relationship between individual subject vamorolone AUC(inf) and dose 
after oral administration of single doses of 0.1, 0.3, 1, 3, 8, and 20 mg/kg 
to healthy subjects under fasted conditions .............................................42 
Figure 3 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) after single dose oral administration of 8 mg/kg to 
healthy subjects under fed and fasted conditions - linear (top panel) 
and semi-logarithmic (bottom panel) axes ...............................................43 
Figure 4 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) on Days 1 and 14 during oral administration of 
1, 3, 9, and 20 mg/kg doses once daily for 14 days to healthy subjects 
under fasted conditions (linear axes) ........................................................46 
Figure 5 
Morning cortisol measures in the vamorolone Phase I MAD 
volunteers.* .................................................................................................48 
Figure 6 
Fasting serum glucose during the Phase I MAD period (two weeks daily 
treatment) ....................................................................................................50 
Figure 7 
Comparisons of serum osteocalcin and CTX1 show no differences of 
placebo compared to 20 mg/kg/day vamorolone.  Within 2 hours prior 
to dosing (pre-dose); 8 hours postdose day 1 (8 hr); 1 day after 14 days 
of dosing (14 day); 3 days after last dose (Rec) ........................................52 
Figure 8 
Pharmacokinetics of 0.25 mg/kg/day vamorolone in 4-7 years DMD 
boys ..............................................................................................................56 
 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition/Term 
ACTH 
adrenocorticotropic hormone 
ADL 
activities of daily living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0-24hr 
area under the concentration-time curve from time 0 to 24 hours 
AUC0-t 
area under the concentration-time curve from time 0 to time t 
AUCinf 
area under the concentration-time curve from time 0 to infinity 
AUClast 
area under the plasma concentration-time curve from time 0 to 
the last observed measurable concentration 
BMI 
body mass index 
BUN 
blood urea nitrogen 
C 
Celsius 
CD23 
cluster designation 23 
CFR 
Code of Federal Regulations 
CINRG 
Cooperative International Neuromuscular Research Group 
CK 
creatine kinase 
CL 
clearance 
ConA 
concanavalin A 
cm 
centimeter 
Cmax 
maximum observed plasma concentration 
CQMS 
CINRG Quantitative Measurement System 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTM 
Clinical Trial Material 
CTX 
carboxy-terminal telopeptide 
CYP 
cytochrome P450 
dL 
deciliter 
DMD 
Duchenne muscular dystrophy 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 

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Abbreviation 
Definition/Term 
EDC 
electronic data capture 
F 
Fahrenheit 
F, F% 
bioavailability, percent bioavailability 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GLDH 
glutamate dehydrogenase 
GLP 
Good Laboratory Practice 
HbA1c 
hemoglobin A1c 
HDL 
high density lipoprotein 
HIPAA 
Health Insurance Portability and Accountability Act 
hr 
hour 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IGFBP-2 
insulin-like growth factor-binding protein 2 
IGFBP-5 
insulin-like growth factor-binding protein 5 
IL-22BP 
interleukin-22 binding protein 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
K2-EDTA 
dipotassium ethylenediaminetetraacetic acid 
kg 
kilogram 
λz 
elimination rate constant 
L 
liter 
LLC 
Limited Liability Company 
LC-MS 
Liquid Chromatography – Mass Spectrometry 
LDH 
lactate dehydrogenase 
LDL 
low density lipoprotein 
m 
meter 
MAD 
multiple ascending dose (study) 
mdx 
mouse model lacking dystrophin 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
min 
minute 
MIST 
Metabolites in Safety Testing 

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Abbreviation 
Definition/Term 
mITT 
modified Intention to Treat 
mL 
milliliter 
MMP-3 
matrix metalloproteinase-3 
MMP-12 
matrix metalloproteinase-12 
MS Band 
Microsoft Band 
NADPH 
nicotinamide adenine dinucleotide phosphate 
NCA 
noncompartmental 
NF-κB 
nuclear factor kappa-light-chain-enhancer of activated B cells 
ng 
nanogram 
No., n 
number 
NOAEL 
no observed adverse effect level 
NSAA 
North Star Ambulatory Assessment 
OTC 
over-the-counter (non-prescription medication) 
%CV 
percentage coefficient of variation 
P1NP 
serum aminoterminal propeptide of type I collagen 
PBL 
peripheral blood leukocytes 
PD 
pharmacodynamics 
PHI 
Protected Health Information 
PK 
pharmacokinetics 
PODCI 
Pediatric Outcomes Data Collection Instrument  
PR [PQ] 
interval from onset of P wave to start of the QRS complex 
Q 
quarter 
QMT 
Quantitative Muscle Testing 
QRS 
in electrocardiography, the complex consisting of Q, R, and S 
waves, corresponding to depolarization of ventricles [complex] 
QSAR 
quantitative structure-activity relationship  
QT 
in cardiology, the interval between the start of the Q wave and 
end of the T wave 
QTcF 
Corrected QT interval using Fredericia’s calculation 
RBC 
Red Blood Cell 
RR 
in electrocardiography, the interval between successive R 
waves (peaks of QRS complexes) 
6MWT 
Six-minute Walk Test 
SAD 
single ascending dose (study) 
SAE 
Serious Adverse Event 
SAP 
statistical analysis plan 
SD 
standard deviation 

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Abbreviation 
Definition/Term 
SOC 
system organ class 
SOP 
standard operating procedures 
SSL 
secure socket layers 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum observed plasma concentration 
TTCLIMB 
Time to Climb (Test) 
TTSTAND 
Time to Stand (Test) 
TTRW 
Time to Run/Walk (Test) 
US 
United States 
vs. 
versus 
Vss 
volume of distribution at steady state 
Vz 
terminal phase volume of distribution 
WBC 
White Blood Cell 
WHO 
World Health Organization 

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1 
INTRODUCTION 
1.1 
Background and Unmet Need 
Duchenne muscular dystrophy (DMD) is a rapidly progressive form of muscular 
dystrophy that occurs primarily in males and manifests prior to the age of six years.  
Duchenne muscular dystrophy affects approximately 1 in 3,600 to 9,300 male births 
worldwide.1  Duchenne muscular dystrophy is caused by mutations in the dystrophin 
gene which codes for a protein that provides structural stability to the dystroglycan 
complex on muscle cell membranes.2  The lack of dystrophin reduces plasma membrane 
stability.  Membrane destabilization results in altered mechanical properties and aberrant 
signaling, which contribute to membrane fragility, necrosis, inflammation, and 
progressive muscle wasting.3 
In addition to the significant contribution of membrane destabilization and mechanical 
injury in DMD, aberrant intracellular signaling cascades that regulate inflammatory and 
immune processes also contribute to DMD pathophysiology.  Up-regulated inflammatory 
gene expression and activated immune cell infiltrates, at least partially mediated by 
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, are 
evident during early disease stages and play a significant role in muscle wasting.3  NF-κB 
has been shown to regulate the expression of numerous inflammatory genes in immune 
cells and muscle fibers,4,5,6,7 and the infiltration and activation of these cells can trigger 
muscle fiber death.8,9 
Although significant advances have been made in understanding the etiology of DMD, a 
cure has not been found, and current treatment options are all medications used “off-
label” to alleviate the symptoms of DMD.  Despite scientific advances, only 
glucocorticoids, such as prednisone, have consistently demonstrated efficacy in clinical 
trials.10  Further, many disease modifying technologies that are currently in development 
focus on subsets of dystrophin mutations and therefore do not address the unmet need in 
all persons with DMD.  However, it is likely that glucocorticoids will need to be 
co-administered with many of these compounds for maximum effect and glucocorticoids 
have extensive side effect profiles, often limiting long-term administration.  The current 

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goal of DMD research is to find a mutation-independent treatment that matches or 
exceeds the efficacy of glucocorticoids with a significantly lower side effect profile. 
Vamorolone is a first-in-class delta-9, 11 chemical compound belonging to the structural 
class of synthetic steroidal drugs, which includes the glucocorticoids prednisone, 
methylprednisone, deflazacort, and dexamethasone.11  The chemical structure of 
vamorolone has optimized four subactivities of traditional glucocorticoid drugs, namely 
transactivation, transrepression, physiochemical membrane properties, and 
mineralocorticoid receptor antagonism.11  By reducing transactivation subproperties, 
retaining transrepression, imparting membrane stabilizing properties, and inhibiting the 
mineralocorticoid receptor pathway, vamorolone has favorable efficacy and side effect 
profiles relative to classic glucocorticoids in nonclinical models and is anticipated to be 
an attractive candidate for the treatment of DMD in pediatric patients. 
In vitro, nonclinical, and clinical (Phase I) data to date suggest that vamorolone may offer 
a much needed alternative to the current glucocorticoids which are standard of care for 
DMD,12 with administration beginning around the age of 5 years in most developed 
countries, or even earlier in some cases. 
The significant effects of glucocorticoids on growth and development, however, prevent 
their routine administration in infancy or ‘toddler’ years, despite evidence that the earlier 
the administration, the better the overall functional outcome.13  The cumulative side 
effects of glucocorticoids, including excess weight, delayed puberty, fragile skin, loss of 
bone mineral density, bruising, and Cushingoid appearance continue to negatively impact 
on the quality of life of the individual, leading to significant variations in clinical 
practice.14  Glucocorticoids also contribute to further muscle damage with long-term 
administration.  Vamorolone has shown few if any of the side effects of traditional 
glucocorticoids in mouse models of DMD.11,15,16 
This study is targeted to explore whether vamorolone will show at least equal efficacy to 
glucocorticoids with a more favorable side effect profile, thereby improving the quality 
of life for DMD patients.  This profile would enable use of vamorolone in DMD boys 
who are at a younger age than when glucocorticoid treatment is currently initiated.  In 

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addition, vamorolone could be prescribed in later stage non-ambulant young men with 
DMD and for a longer period of time, or in very young infants or neonates with DMD, 
where the risk:benefit balance of glucocorticoids is often less favorable. 
Efficacy may also be improved over classic glucocorticoids in the longer term.  In 
addition to the anti-inflammatory properties of vamorolone as a result of NF-κB pathway 
inhibition, vamorolone may also improve efficacy over conventional glucocorticoids due 
to the lack of interference in the AKT1/FOXO pathway, a key feature of glucocorticoid 
therapy which leads in the long term to muscle wasting and atrophy.17  Further, 
vamorolone has been recently demonstrated to improve asynchronous remodeling, 
believed to be a component of progressive muscle weakness and wasting in DMD.18  
Vamorolone is an antagonist to the mineralocorticoid receptor, whereas glucocorticoids 
are typically agonists.  An antagonist for the mineralocorticoid receptor, epleronone, was 
recently shown to significantly improve DMD heart function.19  Finally, vamorolone 
imparts physical stability to myofiber plasma membranes, whereas prednisone 
destabilizes membranes.  This property addresses the primary defect of membrane 
instability in dystrophin deficient myofibers in DMD.15 
Potentially, the administration of vamorolone to a DMD patient may begin soon after 
birth to slow the dystrophic process of muscle, retaining regenerative capacity and 
substantially improving patient quality of life. 
1.2 
Nonclinical Experience 
The safety pharmacology, pharmacokinetics (PK) and metabolism, and toxicology of 
vamorolone have been evaluated in multiple nonclinical studies in vitro and in mice, rats, 
beagle dogs, and cynomolgus monkeys in vivo. 
1.2.1 
Safety Pharmacology 
Stunted growth is a significant side effect of chronic glucocorticoid use in children.20,21  
Chronic treatment with glucocorticoids negatively affects bone growth and development 
and can cause osteoporosis.22,23 

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The effect of vamorolone as compared to prednisolone on bone growth and development 
was evaluated in the mdx mouse model of DMD that lacks dystrophin due to a premature 
chain-terminating mutation in the mouse homologue of the dystrophin gene.  In the pre-
symptomatic mdx study, tibia length was measured to determine if vamorolone inhibited 
bone growth.  Prednisolone significantly decreased tibia length whereas vamorolone did 
not affect tibia length at any concentration tested.  Micro-computed tomography was 
performed on femurs to examine bone density and structure.  Comparison of vehicle, 
prednisolone, and the highest vamorolone dose showed prednisolone to significantly 
reduce trabecular thickness compared to vehicle, while vamorolone did not.15 
In normal, male CD-1® mice, these effects were reproduced.  Unlike CD-1 mice treated 
with prednisolone, CD-1 mice receiving vamorolone did not experience tibia length 
shortening.16  However, at the highest vamorolone dose tested, mice did have 
significantly reduced body length, though to a lesser extent as compared to prednisolone. 
Duchenne muscular dystrophy is associated with cardiomyopathy that can become life 
threatening, and increased fibrosis with prednisone treatment in heart muscle of the mdx 
mouse has been reported.24  Histologically, clear fibrosis was evident in 50% of young 
(8-week) prednisolone-treated mouse hearts compared to no incidence of fibrosis 
identified in the other groups (wild type; mdx vehicle, and vamorolone -treated). 
Pharmacologically, glucocorticoids show immunosuppressive and immunotoxic 
properties that limit therapeutic windows and long-term use.  Vamorolone (5, 15, 
30 mg/kg/day) was benchmarked against prednisolone (5 mg/kg/day) to determine if 
similar properties were observed.15  Untreated mdx mice showed increased numbers of 
peripheral blood leukocytes (PBL) and enlarged spleens resulting from ongoing muscle 
damage compared to wild type mice.  Vamorolone treatment reduced spleen mass and 
PBL counts in a dose-dependent manner.  This finding is attributed to a reduction in 
muscle damage by vamorolone that decreases spleen size to levels resembling those in 
wild type mice.  Prednisolone reduced these measures below wild type, suggesting 
immunosuppressive and/or immunotoxic properties.  Further, prednisolone significantly 
decreased viable splenocytes per gram of tissue (p<0.005), whereas this decrease was not 

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observed for any vamorolone dose tested (ReveraGen Report No. MDX-RBP-VBP15-
02).15 
To further query the potential immune modulation, the effects of vamorolone and 
prednisolone on counts of splenic B and T-lymphocytes isolated from treated mdx mice 
were examined.  CD4+ T-cell activation was assayed by stimulation of splenocytes with 
the T-cell mitogen, concanavalin A (ConA).  Splenocytes obtained from prednisolone-
treated mice displayed a significant reduction of the percentage of splenic activated 
CD4+CD25+ T-cells upon ConA stimulation while splenocytes derived from 
vamorolone-treated mice did not (ReveraGen Report No. MDX-RBP-VBP15-02). 
Taken together, these findings suggest that while prednisolone treatment leads to a 
reduction in T-cell number and activation status, vamorolone modulates inflamed mdx 
immune systems towards a wild type state without compromising T-cell activation status. 
1.2.2 
Pharmacokinetics and Metabolism 
1.2.2.1 
Single Dose 
Vamorolone PK profiles were determined in male CD-1 mice, Sprague Dawley rats and 
beagle dogs after a single intravenous injection of 10 mg/kg and after a single oral dose 
of 50 mg/kg in mice and rats and 30 mg/kg in dogs. 
Pharmacokinetic results for vamorolone following a single intravenous administration of 
10 mg/kg in Crl:CD1(ICR) mice demonstrated a clearance (CL) of 18.8 mL/min/kg.  The 
terminal half-life (t½) was 0.35 hours.  Volume of distribution at steady state (Vss) was 
0.76 L/kg.  Following oral administration of 50 mg/kg in mice, the maximum observed 
plasma concentration (Cmax) of 6787 ng/mL was observed at 2 hours (time to maximum 
observed plasma concentration [Tmax]) after drug administration, and percent 
bioavailability (F%) was 74.5%.  Following oral administration of 15 mg/kg via cherry 
syrup, the Cmax of 1527 ng/mL was observed at 2 hours after drug administration and 
bioavailability was 47.7% (ReveraGen Report No. PH-DPMK-VBP-10-004). 
Pharmacokinetic results for vamorolone following a single intravenous administration of 
50 mg/kg in Sprague Dawley rats indicated a CL of 20.2 mL/min/kg. The t½ was 

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0.58 hours.  Vss was 0.77 L/kg, which was similar to that observed in mice.  After oral 
administration of 50 mg/kg in rats, a Cmax of 2543 ng/mL was observed at 4 hours after 
dose administration, and bioavailability was 47.8% (ReveraGen Report No. PH-DPMK-
VBP-10-007). 
In beagle dogs, vamorolone had a CL of 24.7 mL/min/kg.  The t½ was 5.42 hours and Vss 
was 1.93 L/kg.  After oral administration of 30 mg/kg in dogs, a Cmax of 814 ng/mL was 
observed at 6 hours after dose administration and bioavailability was 53.2% (ReveraGen 
Report No. 48504-10-464). 
Vamorolone clearance was therefore comparable in all 3 species studied 
(19-25 mL/min/kg).  Bioavailability ranged from approximately 50% in mouse (cherry 
syrup), rat, and dog to 75% in the mouse (30% Labrafil) (ReveraGen Report Nos. 
PH-DPMK-VBP-10-004, PH-DPMK-VBP-10-007, 48504-10-464). 
1.2.2.2 
Multiple Dose 
Crl:CD1(ICR) mice were administered vamorolone or vehicle once daily for 
28 consecutive days.  Vamorolone exposure (as assessed by the Cmax and area under the 
concentration-time curve [AUC]) increased with increasing dose on Study Days 1 and 28.  
Repeated dosing of vamorolone over a 28-day duration was associated with decreases in 
mean vamorolone AUClast values in the 30 and 100 mg/kg dose groups compared to 
Day 1, indicating possible enzyme induction.  On Study Day 28, mean AUClast values 
were 1.81-fold and 5.02-fold lower compared to Study Day 1 for the 30 and 100 mg/kg 
dose groups, respectively.  The observed difference in exposure relative to Day 1 
increased with the increase in administered dose of vamorolone (ReveraGen Report No. 
1998-009). 
Beagle dogs were either administered vamorolone or vehicle once daily for 28 
consecutive days.  Vamorolone exposure in dogs (as assessed by Cmax and AUClast) 
generally increased with increasing dose on Study Days 1 and 28.  For the 2 and 10 
mg/kg dose groups, exposure on Day 28 was generally higher than on Day 1, indicating 
possible inhibition of metabolism of vamorolone at these dose levels.  On Day 28, mean 
AUClast values were 2.35-fold and 2.43-fold (males) and 3.03-fold and 3.23-fold 

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(females) higher compared to Study Day 1 for the 2 and 10 mg/kg/day dose groups, 
respectively.  For the 50 mg/kg dose group, exposure on Day 28 was similar to that on 
Day 1.  At the 50 mg/kg dose, AUClast values in males were 1.71-fold lower whereas 
females were 1.22 higher on Day 28 compared to Day 1 (ReveraGen Report No. 
031302). 
Beagle dogs were administered vehicle or vamorolone at doses of 2 mg/kg/day, 
10 mg/kg/day, or 50 mg/kg/day for 39 weeks.  Systemic exposure (AUC0-24hr) to 
vamorolone appeared to be independent of sex.  Mean AUC0-24hr and Cmax values for 
vamorolone increased with increasing dose in an approximately dose proportional 
manner on Days 1 and 270.  Mean systemic exposure (AUC0-24hr) to vamorolone 
appeared to increase following repeated administration of vamorolone.  Due to the 
alterations in the feeding regimen, changes in systemic exposure following repeated 
administration should be viewed with caution due the influence of feeding on exposure.  
For the 2 and 10 mg/kg/day dose groups, exposure on Day 270 was generally higher than 
on Day 1, indicating possible inhibition of metabolism of vamorolone at these dose 
levels.  On Day 270, mean AUC0-24hr values were 2.34-fold and 2.98-fold higher 
compared to Study Day 1 for the 2 and 10 mg/kg/day dose groups, respectively.  For the 
50 mg/kg dose group, exposure on Day 270 was 2.07-fold higher compared to that on 
Day 1 (ReveraGen Report No. 1998-014). 
Non-naïve cynomolgus monkeys were administered vamorolone (300 and 
600 mg/kg/day) or vehicle once daily for 7 consecutive days.  Vamorolone exposure (as 
assessed by Cmax and AUClast) generally increased with increasing dose on Study Days 1 
and 7 with the exception of male monkeys on Day 7, which showed no clear increase in 
exposure between the 300 and 600 mg/kg/day dose levels.  Repeated dosing over the 
7-day study duration was associated with decreases in mean plasma vamorolone AUClast 
values for female and male monkeys indicating possible metabolic induction.  On Day 7, 
mean AUClast values were 1.60-fold, 2.19-fold, and 2.02-fold lower in females and 
1.20-fold, 2.09-fold, and 2.88-fold lower in males compared to Study Day 1 for the 100, 
300 and 600 mg/kg/day dose groups, respectively (ReveraGen Report Nos. 1998-001, 
SW11-0418). 

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1.2.2.3 
Distribution 
In the plasma protein binding studies, percent bound was similar in human and mouse 
cells in culture (88.06% and 86.71%, respectively).  In the blood partition experiment 
done ex vivo, the blood to plasma ratio was similar between human and mouse (0.87 and 
0.68, respectively), but the red blood cell to plasma ratio for the mouse (0.33) was less 
than half that of the human (0.74).  Human in vivo data are presented in Section 1.3 
(VBP15-001).  In the blood/brain concentration mouse experiment in vivo, the plasma 
concentrations of vamorolone were higher than brain concentrations with the AUC and 
Cmax approximately 2-fold higher in plasma than in brain (ReveraGen Report Nos. 
ADME-NCG-PPB-NC135, ADME-VBP-PPB-V002, ADME-NCG-BP-NC134, NCATS 
2013-38). 
1.2.2.4 
Metabolism 
The in vitro and in vivo data demonstrate that vamorolone can be metabolized via 
multiple metabolic pathways, including glucuronidation, hydroxylation, and reduction.  
Glucuronidation appeared to be the major metabolic pathway in human cells in vitro.  All 
metabolites observed in human in vitro were observed in monkey in vitro.  Most human 
metabolites identified in vitro were also found in mouse and dog.  Thus, there is no 
unique human metabolite identified for vamorolone. 
The metabolic stability of vamorolone was assessed in non-Good Laboratory Practice 
(GLP) studies.  Based on the data generated, vamorolone was highly stable for up to 
60 minutes in human, monkey, dog, and mouse liver microsomes in the presence or 
absence of nicotinamide adenine dinucleotide phosphate (NADPH) and stable for up to 
60 minutes in rat liver in the absence of NADPH.  Moderate metabolism was apparent in 
rat liver microsomes in the presence of NADPH stimulation (35% remaining), suggesting 
that rat was a high metabolizer of vamorolone relative to other species (mouse, dog, 
human) (ReveraGen Report Nos. NIH-R2526, and ADME-VBP-LM-V003). 
Vamorolone did not significantly inhibit any of the cytochrome P450 (CYP) enzyme 
isoforms tested (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4).  Vamorolone 
moderately induced CYP3A4 (24% to 42%), indicating that vamorolone is a potential 

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inducer of CYP3A4 (ReveraGen Report Nos. ADME-VBP-Inhibition-V005, ADME-
VBP-Induction-V006, ADME-VBP-Induction-V009). 
1.2.2.5 
Excretion 
Vamorolone showed high plasma clearance in rats but, consistent with the extensive 
metabolism in hepatocytes from this species, the biliary and urinary excretion of the 
parent compound was low with an average of <0.05% of the dose recovered in bile and 
approximately 0.1% in urine.  Overall, vamorolone showed high plasma clearance and 
extremely low biliary and urinary excretion (ReveraGen Report No. NCATS 2013-44). 
1.2.3 
Toxicology 
1.2.3.1 
Single Dose 
Crl:CD1(ICR) mice were administered vamorolone once via oral gavage at 50, 125, 250, 
and 500 mg/kg and observed for abnormalities.  All animals survived to their scheduled 
termination, and there were no significant abnormalities observed.  There was a slight 
decrease in body weight attributed to vamorolone in both males and females at doses 
above 125 mg/kg.  A dose dependent decrease in food consumption related to 
vamorolone was also observed in males and females.  No other abnormalities were 
observed in experimental mice (ReveraGen Report No. 1998-002). 
Beagle dogs received single 60, 180, 360, and 750 mg/kg doses of vamorolone using an 
escalation study design with a 4-day washout period between doses.  All animals 
survived dose escalation.  Clinical signs attributed to vamorolone (750 mg/kg) included 
red discoloration of the ears and face.  This effect occurred within a few hours of dosing 
and was transient.  The highest dose also resulted in increased white blood cell count 
(increased neutrophils and monocytes [female only] and decreased lymphocytes and 
eosinophils [male and female]).  At the 360 and 750 mg/kg dose levels, slight elevations 
in albumin were observed.  A mild elevation in cholesterol at the 750 mg/kg (and 
possibly 360 mg/kg) dose level was also observed (ReveraGen Report No. 13788.01.01). 
In cynomolgus monkeys, single oral doses of up to 500 mg/kg were well tolerated with 
no significant abnormalities observed (ReveraGen Report No. 1998-001). 

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1.2.3.2 
Multiple Dose 
Vamorolone or vehicle was administered to Crl:CD1(ICR) mice once daily for 28 
consecutive days at doses of 10, 30 and 100 mg/kg/day.  All animals survived to their 
scheduled necropsy with the exception of a female mouse (100 mg/kg/day dose group) 
that was found dead on Day 16.  The cause of death was considered incidental and 
attributed to a dosing injury based on the amount of red fluid in the thoracic cavity. 
No effects attributable to vamorolone were observed in food consumption, ophthalmic 
examination, or urinalysis during the study.  Dose-dependent decrease in body weight 
gain was observed at all doses; however, weight was fully regained during the recovery 
period.  Adrenal gland weights were variable between groups and generally decreased, 
but without a dose response relationship, and correlated microscopically with minimal to 
moderate vacuolar degeneration and cortical atrophy.  After the 2-week recovery period 
there was evidence of vacuolar degeneration of the adrenal gland.  Liver weights were 
significantly increased at the 100 mg/kg/day dose level.  Hepatocellular hypertrophy, 
increased vacuolation, and necrosis (single cell) were seen in a few male mice at 
30 mg/kg/day.  There was evidence of lipid and glycogen accumulation.  Serum alanine 
aminotransferase and aspartate aminotransferase levels were higher with associated 
microscopic hypertrophy/vacuolation/necrosis at 100 mg/kg/day.  Spleen weights 
decreased in a dose-dependent manner and correlated with a decreased number of 
lymphocytes in spleen.  Thymus weights decreased in a dose dependent manner and were 
associated microscopically with lymphoid atrophy.  Mice had dose-dependent reductions 
in serum lymphocytes which were significant in the 100 mg/kg dose group.  After the 
recovery period, all parameters returned to normal (untreated) except for thymus weights, 
which were increased. 
Based on the liver-related findings in this study, the no observed adverse effect level 
(NOAEL) for vamorolone in mice is 30 mg/kg/day (ReveraGen Report No. 1998-009). 
Vamorolone or vehicle was administered to beagle dogs once daily for 28 consecutive 
days at doses of 2, 10 and 50 mg/kg/day.  All animals survived to their scheduled 
termination and no effect of vamorolone was noted on gross visual inspection, body 

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weight, body temperature, food consumption, ophthalmology, electrocardiography or 
urinalysis parameters at necropsy.  A dose-dependent decrease in the expected normal 
body weight gain was observed at all doses but weights generally increased to a normal 
level during the recovery period. 
Adrenal gland weights decreased with vamorolone treatment, which correlated with mild 
or moderate diffuse bilateral atrophy of the adrenal cortex, mild multifocal bilateral 
vacuolation of the adrenal cortex, increased white blood cell and neutrophil counts, and 
decreased eosinophil counts.  Liver weights increased in the 50 mg/kg/day dose group, 
which correlated with diffuse hypertrophy and vacuolation and increased levels of 
alkaline phosphatase and gamma glutamyltransferase.  Spleen weights decreased, which 
correlated with lymphoid depletion.  Thymus weights decreased, which corresponded to 
diffuse lymphoid depletion.  With the exception of diffuse depletion of lymphocytes in 
thymus in the 50 mg/kg group, all abnormal parameters returned to normal during the 
recovery period. 
The NOAEL was considered by the study director to be 10 mg/kg/day.  Although 
reversible, the liver changes were considered adverse at 50 mg/kg/day because the 
severity score was moderate and the changes were diffuse in nature in all animals treated 
at the high dose.  This determination is in contrast to the conclusion drawn by the study 
pathologist, who considered the NOAEL to be 50 mg/kg/day due to reversibility 
following cessation of dosing (ReveraGen Report No. 31302). 
Vamorolone or vehicle was administered to beagle dogs once daily for 39 weeks at doses 
of 2, 10 and 50 mg/kg/day.  Six dogs of each sex received each dose or placebo, and two 
of the six dogs of each sex at each dose or placebo were followed for an additional 
4 weeks to evaluate reversibility, progression, or delayed appearance of any observed 
changes.  One male dog that received 50 mg/kg/day was euthanized in extremis on Day 
273 due to paraphimosis (an extended penis).  All other animals survived to their 
scheduled termination. 
Detailed clinical observations considered test article-related at 50 mg/kg/day, and 
reversible, included decreased activity (considered adverse), struggling during dosing, 

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feces soft, limb function impaired, interdigital cysts, and unkempt appearance 
(considered adverse).  Test article-related, dose-dependent increases in body weight gains 
correlating with increases in food consumption were observed relative to controls in 
males at all dose levels and in females at 10 and 50 mg/kg/day.  Test article-related, 
reversible increases in average mean food consumption, relative to controls, over the 
course of the 39-week dose phase were observed in both sexes at 10 and 50 mg/kg/day. 
No test article-related ophthalmological effects were noted.  No test-article-related 
changes were noted in respiratory rates or rectal temperatures.  There may have been a 
mild dose-related reversible increase in the heart rate at the terminal post-dose interval 
that was significantly different from vehicle in both sexes following the 50 mg/kg/day 
dose.  Semen analysis/evaluation for test article affects could not be conducted as there 
were not enough viable samples collected. 
Test article-related effects on clinical pathology endpoints with microscopic correlates 
included the following: 
• A hepatocellular and hepatobiliary effect in males at 10 mg/kg/day and both sexes 
at 50 mg/kg/day, which included increased alkaline phosphatase, gamma 
glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase 
activity.  These changes correlated with microscopic changes in the liver, bile 
duct, and gall bladder.  This spectrum of changes was considered adverse in both 
sexes at 50 mg/kg/day. 
• There was also evidence of an inflammatory response in both sexes at 
50 mg/kg/day, which included increased total leukocyte, neutrophil, and 
monocyte counts, and increased fibrinogen and/or globulin concentrations.  The 
inflammatory response was likely secondary to inflammation in the liver 
associated with hepatocellular necrosis.  Platelet counts were also increased in 
both sexes at 50 mg/kg/day and may have been secondary to the inflammatory 
response. 

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Following a 4-week recovery period, all noted clinical pathological changes resolved, 
with the exceptions of increased alanine aminotransferase activity in both sexes at 
50 mg/kg/day, and increased globulin in males at 50 mg/kg/day. 
Reversible, test article-related macroscopic findings included mildly to moderately 
enlarged livers in males and females at 50 mg/kg/day, which correlated microscopically 
with panlobular hepatocellular hypertrophy and/or hepatocellular vacuolation; 
hemorrhage in the gall bladder of one 50 mg/kg/day female, that was associated with 
moderate acute inflammation and mild vascular necrosis, and considered to be adverse; 
red focus/foci within the pylorus of the stomach of one 50 mg/kg/day female and one 
male at 10 mg/kg/day, which correlated microscopically with mild acute inflammation in 
the female. 
Test article-related organ weight changes at the terminal necropsy included decreases in 
adrenal gland weights in both sexes at ≥ 2 mg/kg/day (microscopic correlate of bilateral 
cortical atrophy); increases in liver weights in both sexes at ≥ 10 mg/kg/day (microscopic 
correlates of panlobular hepatocellular hypertrophy and/or hepatocellular vacuolation); 
increases in kidney weights in females at ≥ 10 mg/kg/day and males at 50 mg/kg/day 
(microscopic correlate of bilateral tubular vacuolation); decreases in prostate gland 
weights in males at 50 mg/kg/day (microscopic correlate of decreased secretory product).  
These organ weight changes were all reversible, except for the decreases in the prostate 
gland.  Microscopic evaluation revealed the following test article-related changes: 
adrenal glands (atrophy of the zona fasciculata and zona reticularis and 
hypertrophy/hyperplasia of the zona glomerulosa in both sexes at ≥ 10 mg/kg/day and 
atrophy was considered adverse); esophagus and pylorus of the stomach 
(erosion/ulceration in a few animals of both sexes at 50 mg/kg/day); gallbladder 
(hypertrophy/hyperplasia of the mucosal epithelium in both sexes at ≥ 10 mg/kg/day and 
cytoplasmic vacuolation of the mucosal epithelium in males at ≥ 10 mg/kg/day and 
females at ≥ 2 mg/kg/day); liver (hepatocellular vacuolation in males at ≥ 10 mg/kg/day 
and females at ≥ 2 mg/kg/day, panlobular hypertrophy in males at 50 mg/kg/day and 
females at ≥ 10 mg/kg/day, and inflammation/necrosis in both sexes at 50 mg/kg/day and 
considered adverse, bile duct hyperplasia in both sexes at 50 mg/kg/day, bile duct 

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hypertrophy in males at 50 mg/kg/day and females at ≥ 10 mg/kg/day, and cytoplasmic 
vacuolation of the bile duct epithelium in both sexes at ≥ 10 mg/kg/day); kidneys 
(bilateral tubular vacuolation in males at 50 mg/kg/day and females at ≥ 10 mg/kg/day 
and an increased incidence of bilateral basophilic tubules in males and females at 
50 mg/kg/day); lymphoid depletion in both sexes at 50 mg/kg/day in mandibular and 
mesenteric lymph nodes, thymus and spleen (with extramedullary hematopoiesis in 
50 mg/kg/day females); bone marrow in the sternum (increased adipocytes in males at 
≥ 2 mg/kg/day and females at 50 mg/kg/day); testes (spermatocyte/spermatid 
degeneration in males at 50 mg/kg/day); epididymides (oligospermia/germ cell debris in 
males at 50 mg/kg/day); ovaries (absent corpora lutea in females at ≥ 2 mg/kg/day and 
considered adverse); the mammary gland and other tissues in the female reproductive 
tract (uterus, cervix, and vagina) of these animals were consistent with animals that have 
not ovulated; vacuolation in the epithelium of the mammary gland duct in females at 
50 mg/kg/day; parotid salivary gland (cytoplasmic alteration in both sexes at 
≥ 10 mg/kg/day); biceps femoris (atrophy of the skeletal muscle in both sexes at 
50 mg/kg/day); skin (atrophy and alopecia/hypotrichosis in males at 50 mg/kg/day and 
females at ≥ 10 mg/kg/day); prostate gland (decreased secretory product in males at 
50 mg/kg/day); thyroid glands (bilateral increased colloid in males at ≥ 10 mg/kg/day). 
Many of the findings were felt by the Study Director to be consistent with the 
pharmacology of the test article including cortical atrophy of the adrenal glands (affecting 
the zona fasciculata and reticularis), generalized lymphoid depletion in lymphoid tissues 
(thymus, spleen, and lymph nodes), increased adipocytes in the bone marrow, atrophy of 
the skeletal muscle, alopecia/hypotrichosis and atrophy of the skin (thinning of the 
dermal collagen and atrophy of hair follicles and adnexa), an absence of corpora lutea in 
the ovary (likely indicative of delayed puberty), decreased secretory product in the 
prostate gland, and multiple changes in the liver.  The liver had panlobular hypertrophy 
and vacuolation of hepatocytes consistent with glycogen accumulation.  Due to the 
magnitude of hypertrophy and vacuolation, there were (likely secondary) foci of 
hepatocellular necrosis and inflammation. 

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Test article-related microscopic findings at the recovery necropsy were present in the 
adrenal glands, liver, gallbladder, kidneys, stomach (pylorus), female reproductive tract 
(ovaries), male reproductive tract (testes, epididymides, prostate gland), mesenteric  
lymph node, skeletal muscle (biceps femoris), and parotid salivary gland. 
The No Observed Adverse Effect Level was 2 mg/kg/day for males; a No Observed 
Adverse Effect Level was not observed for females (ReveraGen Report No. 1998-014).  
Non-naive cynomolgus monkeys were administered vamorolone or vehicle once daily for 
7 consecutive days at doses of 100, 300, and 600 mg/kg.  All animals survived until the 
end of the study period.  There were effects on clinical observations, food consumption, 
and urinalysis attributable to vamorolone that are described below. 
There was a dose proportional decrease in body weight gain observed in males and 
females at each dose (up to 11% and 9% respectively) related to vamorolone.  A 
cessation of the body weight loss in treatment was observed during the recovery phase 
but no recovery of body weight lost during the 7 days of dosing was observed. 
At termination there were nonsignificant increases in red cell mass and decreases in 
lymphocytes (up to 56%) in the 600 mg/kg/day dose group.  However, most individual 
animals, including controls, had decreases in lymphocytes (up to 81%) at termination 
relative to their respective pretest.  They had resolved by the recovery interval in both 
sexes. 
In both sexes receiving ≥ 300 mg/kg/day, there was increased urea nitrogen (up to 141%), 
creatinine (up to 58%), total protein (up to 15%), albumin (up to 11%), globulin (up to 
25%), and/or potassium (up to 39%) with concurrent decreases in sodium (up to 10%) 
and chloride (up to 10%) relative to controls.  At the recovery interval, the majority of 
these effects had resolved (ReveraGen Report No. 1998-001). 
1.2.3.3 
Genotoxicity 
The mutagenic and genotoxic potential of vamorolone was assessed in several assays.  A 
non-GLP Ames screen was negative for bacterial mutations (ReveraGen Report No. 
BIO-VBP-001-AMES).  In a GLP Ames test, no background lawn toxicity was observed; 

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however, a reduction in revertant counts was observed (ReveraGen Report No. 
AD79DT.502ICH.BTL).  Vamorolone was negative for inducing chromosomal 
aberrations in cultured mouse lymphocytes without and with metabolic activation 
(ReveraGen Report No. AD79DT.704.BTL). 
Femoral bone marrow was microscopically evaluated for the presence of polychromatic 
erythrocytes (PCEs) containing micronuclei.  No significant reductions in the PCEs/EC 
(total erythrocytes) ratio were observed in the vamorolone groups compared to the 
vehicle control group.  Although statistically significant increases in the incidence of 
micronucleated PCEs in the vamorolone treated groups were observed, no dose response 
was observed with respect to other groups and the values of micronuclei for the 
individual animals were within the historical range.  Therefore, the statistically 
significant increase was considered as biologically insignificant (ReveraGen Report No. 
AD76BK.123012ICH.BTL). 
A study was performed to evaluate the potential mutagenicity of two theoretical epoxide 
impurities related to the drug substance vamorolone (formerly VBP15), which is a 
steroid-like structure containing a delta 9,11 double bond.  The delta 9,11 epoxide 
structures evaluated were VBP15-B-3, which is structurally similar to vamorolone except 
for the epoxide moiety, and VBP15-B-2, which has a 21-acetate substitution (vamorolone 
and VBP15-B-3 contain a 21-hydroxy moiety).  Two validated and complementary 
in silico prediction methodologies were used for assessing mutagenic potential.  The 
statistics-based quantitative structure-activity relationship (QSAR) program MultiCASE 
CASE Ultra was used, employing four different modules (GT1_A7B, GT1_AT_ECOLI, 
PHARM_ECOLI, and PHARM_SAL) designed to cover a wide range of molecular 
substructures collected from both proprietary and public compounds.  In addition, the 
expert rule-based SAR program Derek Nexus was used to determine if the theoretical 
impurities contained structural alerts associated with known genotoxicants.  CASE Ultra 
predicted both VBP15-B-2 and VBP15-B-3 as negative for mutagenicity [ReveraGen 
Report “In Silico Mutagenicity Evaluation of Delta 9,11 Epoxide Structures of VBP15: 
VBP15-B-2 (21-Acetate) and VBP15-B-3 (21-Hydroxy)”]. 

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Taken together, these data indicate vamorolone has not generated a mutagenic signal 
based on these simulations. 
1.3 
Clinical Experience 
1.3.1 
Phase I Study in Healthy Adult Volunteers 
Clinical experience is limited to a single Phase I clinical trial of vamorolone in healthy 
adult volunteers (VBP15-001).  This study evaluated the safety, tolerability, and PK of 
vamorolone in a Phase I randomized, placebo-controlled, double-blind, single ascending 
dose (SAD) and multiple ascending dose (MAD) study.  In the SAD portion of the study, 
Cohorts 1 through 5 and Cohort 7 were comprised of eight subjects each; six subjects in 
each cohort received a single oral dose of vamorolone (0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg, 
3.0 mg/kg, 8.0 mg/kg, and 20 mg/kg, respectively) and two subjects in each cohort 
received placebo under fasted conditions.  In Cohort 6, six subjects received a single oral 
dose of 8.0 mg/kg vamorolone within 30 minutes of beginning a high fat/high calorie 
meal.  The MAD portion of the study had four cohorts (6 drug, 2 placebo in each) 
receiving 14 daily doses of vamorolone (1.0, 3.0, 9.0 and 20.0 mg/kg/day).  The clinical 
conduct for all seven SAD cohorts and all four MAD cohorts has been completed. 
The primary objectives of the Phase I study were to evaluate the safety and tolerability of 
single and multiple oral doses of vamorolone, and to evaluate the PK of single doses and 
multiple doses of vamorolone.  A secondary objective was to evaluate the effect of food 
on the absorption and PK of vamorolone.  Other objectives were to obtain samples from 
subjects on Day 1 (pre-dose) and Day 14 of the MAD cohorts for use in Metabolites in 
Safety Testing (MIST) assessments, and to test back-up PK samples from a subset of 
MAD subjects for pharmacodynamic (PD) biomarkers. 
1.3.1.1 
SAD Cohorts 
1.3.1.1.1 
SAD Cohorts – Pharmacokinetics Fasted 
Vamorolone PK data shows strong adherence to dose linearity and dose proportionality, 
with relatively little subject-subject variation (Figure 1, Table 1, Figure 2).  The half-life 

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was about 2 hours for doses 0.1-1.0 mg/kg.  Doses at 3.0, 8.0 and 20.0 mg/kg showed an 
extended tail, increasing half-life to 2.5, 3.8 and 3.8 hours, respectively (Figure 1). 
 
Figure 1 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) after oral administration of single doses of 0.1, 0.3, 
1, 3, 8, and 20 mg/kg to healthy subjects under fasted conditions - linear 
plot (top); semi-logarithmic plot (bottom) 
 
 

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Table 1 
Summary of pharmacokinetic parameters for vamorolone after oral 
administration of single doses of 0.1, 0.3, 1.0, 3.0, 8.0, and 20.0 mg/kg to 
healthy subjects under fasted conditions 
 
Cmax = maximum observed plasma concentration; Tmax = time to maximum observed plasma concentration; AUC(0-t) = 
area under concentration-time curve from time 0 to time t; AUC(inf) = area under concentration-time curve from time 0 
to infinity; λz = elimination rate constant; t½ = terminal half-life; CL/F = apparent total clearance from plasma; Vz/F = 
apparent volume of distribution during terminal phase. 
Figure 2 
Relationship between individual subject vamorolone AUC(inf) and dose 
after oral administration of single doses of 0.1, 0.3, 1, 3, 8, and 20 mg/kg 
to healthy subjects under fasted conditions 
 

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1.3.1.1.2 
SAD Cohorts – Pharmacokinetics Fed 
For the food effect group, a high fat meal (45 grams fat) was given to a cohort of Phase I 
SAD volunteers with the 8.0 mg/kg dose of vamorolone.  These data were then compared 
to the fasted 8.0 mg/kg cohort data.  This showed that absorption was increased by 
2.5-fold by the high fat meal, consistent with the lipophilic character of vamorolone 
(steroidal compound) (Figure 3, Table 2). 
Figure 3 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) after single dose oral administration of 8 mg/kg to 
healthy subjects under fed and fasted conditions - linear (top panel) and 
semi-logarithmic (bottom panel) axes 
 
 

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Table 2 
Summary of pharmacokinetic parameters for vamorolone after single 
dose oral administration of 8 mg/kg to healthy subjects under fed and 
fasted conditions 
 
*Geometric mean (%CV) (N) except Tmax for which the median (N) is reported. 
†Ratio of the geometric means. 
Cmax = maximum observed plasma concentration; Tmax = time to maximum observed plasma concentration; AUC(0-t) = 
area under concentration-time curve from time 0 to time t; AUC(inf) = area under concentration-time curve from time 0 
to infinity; λz = elimination rate constant; t½ = terminal half-life; CL/F = apparent total clearance from plasma; Vz/F = 
apparent volume of distribution during terminal phase. 
1.3.1.1.3 
SAD Cohorts – Adverse Events 
One subject in the SAD 8.0 mg/kg showed a delayed mild elevation of liver enzymes.  
These elevations were not felt to be drug-related due to timing of the elevations.  
Unblinding revealed that the subject had received placebo.  There were no other adverse 
events (AEs) seen in any dose group. 
1.3.1.2 
MAD Cohorts  
The Phase I MAD treatment plan was discussed in light of the initial PK data.  The 
relatively short half-life of vamorolone (2-4 hours), coupled with the planned daily dose 
schedule, would be expected to give PK data on each single dose, not cumulative dose, as 
the dosing interval was > 5 × t½.  Thus, the MAD component would be a study of 
individual daily doses, rather than dose-related accumulation and pharmacodistribution 
related to cumulative drug exposure.  In other words, a typical goal of a MAD study is to 
determine steady state drug levels after multiple doses; yet with the short half-life of 
vamorolone, useful information would not be expected to be gained with the current daily 

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dosing schedule.  Safety and tolerability are additional goals of the MAD study, and these 
remain important endpoints independent of the PK studies. 
1.3.1.2.1 
MAD Cohorts – Pharmacokinetics Fasted 
The original design for the Phase I MAD was modified to remove the two lowest doses 
(0.1, 0.3 mg/kg/day), and to begin dosing at 1.0 mg/kg/day.  The clinical conduct of all 
four cohorts has been completed (1.0 mg/kg/day, 3.0 mg/kg/day, 9.0 mg/kg/day, 
20.0 mg/kg/day) for the MAD study (Table 3). 
Table 3 
Summary of pharmacokinetic parameters for vamorolone during oral 
administration of 1, 3, 9, and 20 mg/kg doses once daily for 14 days to 
healthy subjects under fasted conditions 
 
Vamorolone Dose 
1 mg/kg 
3 mg/kg 
9 mg/kg 
20 mg/kg 
Day 1 
Cmax (ng/mL) 
153 (15.9) 
281 (36.9) 
1,082 (23.3) 
2,416 (51.1) 
Tmax (hr) 
3.04 
2.01 
1.75 
1.00 
[1.50 – 4.00] 
[1.00 – 3.00] 
[1.00 – 6.00] 
[0.50 – 3.00] 
AUC(0-t) (hrxng/mL) 
686 (22.4) 
1,471 (23.6) 
5,709 (29.9) 
10,182 (28.1) 
AUC(0-24) (hr×ng/mL) 
686 (22.4) 
1,471 (23.6) 
5,709 (29.9) 
10,182 (28.1) 
AUC(inf) (hr×ng/mL) 
695 (22.1) 
1,487 (23.7) 
5,745 (29.5) 
10,190 (27.0) 
λz (1/hr) 
0.3848 (10.9) 
0.2918 (18.1) 
0.2317 (22.6) 
0.1747 (44.3) 
t½ (hr) 
1.80 (10.9) 
2.38 (18.1) 
2.99 (22.6) 
3.97 (44.3) 
CL/F (L/hr/kg) 
1.44 (22.1) 
2.02 (23.7) 
1.57 (29.5) 
1.96 (27.0) 
Vz/F (L/kg) 
3.74 (16.9) 
6.91 (34.8) 
6.76 (46.9) 
11.2 (77.6) 
Day 14 
Cmax (ng/mL) 
203 (30.1) 
276 (35.6) 
935 (48.3) 
2,491 (27.9) 
Tmax (hr) 
2.96 
2.50 
1.25 
2.00 
[1.50 – 3.00] 
[1.00 – 4.00] 
[0.55 – 3.00] 
[1.00 – 2.00] 
AUC(0-24) (hr×ng/mL) 
794 (22.3) 
1,494 (18.6) 
4,366 (20.2) 
9,309 (38.8) 
λz (1/hr) 
0.3993 (20.4) 
0.3273 (25.2) 
0.1629 (63.5) 
0.1879 (31.6) 
t½ (hr) 
1.74 (20.4) 
2.12 (25.2) 
4.25 (63.5) 
3.69 (31.6) 
CL/F (L/hr/kg) 
1.26 (22.3) 
2.01 (18.6) 
2.06 (20.2) 
2.15 (38.8) 
Vz/F (L/kg) 
3.15 (20.6) 
6.14 (39.7) 
12.7 (79.9) 
11.4 (49.1) 
Cmax = maximum observed plasma concentration; Tmax = time to maximum observed plasma concentration; AUC(0-t) = 
area under concentration-time curve from time 0 to time t; AUC(0-24) = area under concentration-time curve from time 0 
to 24 hours; AUC(inf) = area under concentration-time curve from time 0 to infinity; λz = elimination rate constant; t½ = 
terminal half-life; CL/F = apparent total clearance from plasma; Vz/F = apparent volume of distribution during terminal 
phase. 

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Taking into account the small numbers and different subjects, the geometric mean values 
for Cmax, AUC(0-t), and AUC(inf) are not different for the SAD and MAD cohorts.  Within 
the MAD, there is good agreement between Days 1 and 14 at all dose groups.  There is no 
accumulation — the geometric mean Cmax and AUC(0-24) on Days 1 and 14 are not 
different, consistent with the t½ (~2 hour) and dosing interval (24 hours) (Figure 4; 
Table 3). 
Figure 4 
Arithmetic mean ± standard error plasma concentrations of 
vamorolone (VBP15) on Days 1 and 14 during oral administration of 
1, 3, 9, and 20 mg/kg doses once daily for 14 days to healthy subjects 
under fasted conditions (linear axes) 
 
 
1.3.1.2.2 
MAD Cohorts – Adverse Events 
Three subjects have discontinued dosing; one subject (1.0 mg/kg/day group) withdrew 
consent on Day 10 so that he could receive care for an exacerbation of a previously 
existing dental condition.  Dosing was discontinued in a second subject on Day 9 (on 
placebo in the 1.0 mg/kg/day cohort after completing 8 days of dosing) due to an increase 
in alanine aminotransferase (ALT).  The subject’s baseline value was 40 (normal ≤ 50); 
on Days 7, 8, and 9, it was 70, 86, and 106, respectively.  Following cessation of dosing, 
the ALT has slowly declined and is continuing to be followed.  Aspartate 

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aminotransferase (AST) was within normal limits with the exception of a value of 47 on 
Day 9 (normal ≤ 45), which was again normal the following day.  Alkaline phosphatase, 
bilirubin, and coagulation parameters have remained within normal limits and the subject 
has remained asymptomatic.  A third subject who was on active drug in the 20 mg/kg 
dose group was discontinued after 9 days of dosing due to an increase in ALT.  The 
subject’s baseline value was 43 (normal ≤ 50) at screening; on Days 7, 8, and 9, it was 
56, 60, and 73, respectively.  Following cessation of dosing, the ALT increased to 96 and 
104 on Days 10 and 12; on Day 17, it had declined to 85.  The subject continues to be 
followed and has remained asymptomatic.  Aspartate aminotransferase was within 
normal limits with the exception of a value of 47 on Day 12 (normal ≤ 45); total bilirubin 
was 0.7 at screening (normal 0.2-1.2); it was increased at 1.4, 1.9, and 1.4 on Days 1, 2, 
and 3, respectively, and within normal limits for the remainder of dosing and follow-up.  
No subject in the 3.0 or 9.0 mg/kg/day cohorts had to discontinue dosing for an AE. 
1.3.1.2.3 
Pharmacodynamic Safety Biomarkers 
Vamorolone has shown improved safety profiles relative to prednisone in nonclinical 
testing, both in vitro and in vivo.15,17  Safety concerns with glucocorticoids include 
suppression of the adrenal axis and insulin resistance.  Pharmacodynamic biomarker 
assays of suppression of the adrenal axis (serum cortisol) and insulin resistance (serum 
glucose) were measured in the Phase I MAD studies of vamorolone. 
Suppression of the adrenal axis.  Prednisone directly impinges on cortisol regulatory 
pathways (adrenal axis) both acutely and chronically.  Acute suppression of adrenal 
function is seen within hours of doses of a single 0.1 mg/kg/day (approximate) dose of 
prednisone, as evidenced by reductions in adrenocorticotropic hormone (ACTH) levels in 
normal volunteers.25  More chronic suppression of the adrenal axis, characterized as 
severe, is typically diagnosed when morning cortisol is < 100 nmol/L (< 3.6 
microgram/dL) when drawn > 24 hrs after the last dose of pharmacological steroids. 
Morning serum cortisol levels were measured in the vamorolone Phase I MAD cohorts, at 
baseline (prior to drug administration), 24 hours after the first dose (Day 1), and 24 hours 
after the 14-day dose (Day 15) (Figure 5).  Active substance volunteers at four MAD 

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dose levels are shown (1.0 mg/kg/day; 3.0 mg/kg/day; 9.0 mg/kg/day; 20.0 mg/kg/day); 
all subjects were treated for 14 days with daily dosing.  The red hatched line on each 
graph shows a typical threshold for adrenal axis suppression (< 100 nmol/L, or 
< 3.6 µg/dL).  P values shown are for paired T test, indicating significance of the 
consistency of longitudinal changes of subjects relative to their own individual baseline 
values.  Acute adrenal axis suppression is measured at 24 hours (after first dose), whereas 
chronic adrenal axis suppression is measured after 14 days of daily dosing (24 hours after 
last dose). 
Figure 5 
Morning cortisol measures in the vamorolone Phase I MAD 
volunteers.* 
* Placebo subjects from each of the four MAD cohorts are graphed together. 
Vamorolone showed little evidence of either acute (24 hour data), or chronic (Day 15 
data) suppression of the adrenal axis at doses of either 1.0 mg/kg/day or 3.0 mg/kg/day.  
The data suggest that vamorolone induces variable, mild, acute and chronic suppression 
of the adrenal axis at 9.0 mg/kg/day, and stronger evidence of both acute and chronic 
adrenal axis suppression at 20.0 mg/kg/day.  Prednisone typically shows both acute and 
chronic adrenal axis suppression approximately at 0.1 mg/kg/day,25 suggesting that 
vamorolone has an improved safety window regarding adrenal axis suppression. 

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Vamorolone thus shows approximately a 100-fold improvement in safety window 
compared to prednisone on a mg/kg comparative basis.  These data are consistent with in 
vitro and ex vivo nonclinical mouse data comparing VBP15/vamorolone to prednisone for 
adrenal suppression.15 
Insulin resistance.  Prednisone induces the safety signal of insulin resistance, where 
glucose is not efficiently taken up from the blood by target tissues, such as muscle and 
liver, leading to hyperglycemia.25  Insulin resistance may be an important safety signal 
for dystrophic muscle, where the dysfunctional myofibers have been shown to have 
inadequate energy stores,18,26 and insulin resistance likely limits availability of glycogen 
substrates for glycolysis.  The hyperglycemia, in turn, leads to chronic increases in 
insulin levels (hyperinsulinemia). 
Levels of fasting glucose and insulin are reasonably sensitive and reliable measures of 
insulin resistance in non-diabetic individuals.  Glucose is acutely (single dose) and 
chronically (multiple doses) elevated after treatment with pharmacological 
glucocorticoids.  Glucose is elevated 24 hours after a single administration of 
glucocorticoids (2.0 mg/kg).27,28 
In the Phase I MAD of vamorolone, fasting serum glucose was measured at 10 time 
points during the 2-week study; each sample was taken 24 hours after the previous dose 
of vamorolone (Figure 6). 

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Figure 6 
Fasting serum glucose during the Phase I MAD period (two weeks daily 
treatment) 
 
Glucose levels for all vamorolone dose groups were similar to those of the placebo group.  
There was no evidence of elevations of glucose levels at any time point or any dose of 
vamorolone, suggesting that the side effect of insulin resistance was not seen with 
vamorolone.  These data are consistent with a nonclinical study in a dystrophin-deficient 
mouse model, where chronic treatment of prednisolone (5 mg/kg/day) versus vamorolone 
(15 mg/kg/day; 30 mg/kg/day) showed development of insulin resistance with 
prednisolone, but not vamorolone.29 
Bone remodeling.  Glucocorticoid side effects impacting bone cause significant 
morbidity. Extensively studied in older adults where glucocorticoids are often given for 
arthritis and other age-related chronic inflammatory states, adjusted relative rate of non-
vertebral fractures shows a dose-dependent increase to 2.5 times non-treated adults, and 
this is directly related to glucocorticoid-induced osteopenia.30  The bone effects in 
glucocorticoid-treated patients with DMD can be even greater because the standard of 
care for boys with DMD is chronic treatment with double the highest glucocorticoid dose 
typically used in older adults.31  Fractures due to osteoporosis are common in patients 
chronically treated with glucocorticoids, both in older adult populations (e.g. arthritis) 

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and in the pediatric population (e.g. Duchenne muscular dystrophy; DMD).  Bone safety 
is a significant cause of clinical morbidity, including vertebral fractures that can lead to 
chronic back pain and spinal deformity, and long bone fractures that have been linked to 
permanent, premature loss of ambulation.32 
Because the initiation of glucocorticoid treatment is recommended in early childhood for 
patients with DMD, the adverse effects of glucocorticoids are amplified through effects 
on bone cellular metabolism, bone growth and puberty. Osteoporosis, manifesting as low-
trauma vertebral or long bone fractures, is frequent in DMD.33  This is not surprising 
given the potent osteotoxicity of glucocorticoid therapy combined with the progressive 
myopathy, both of which are key risk factors for reduced bone strength.  Studies have 
reported that 20 to 60% of boys with DMD have low-trauma extremity fractures (usually 
of the distal femur or tibia/fibula) while up to 30% develop symptomatic vertebral 
fractures during the pediatric years.34,35,36  The number of symptomatic vertebral fractures 
that have been reported to date suggests the true vertebral fracture prevalence is likely 
higher, since vertebral fractures are frequently asymptomatic when identified in children 
with other glucocorticoid-treated illnesses through a monitoring program that includes a 
lateral spine radiography37.  Untreated, vertebral fracture lead to chronic back pain and 
spine deformity, while leg fractures can cause premature, permanent loss of ambulation.25  
Death due to fat embolism syndrome and subsequent respiratory distress after long bone 
fractures in both ambulant and non-ambulant patients has also been reported in DMD.38,39  
A recent study found that osteoporosis treatment with bisphosphonates may improve 
survival in DMD, emphasizing the urgency for effective osteoporosis diagnosis, 
monitoring and prevention strategies.40 
Bone turnover markers are often used to monitor effects of drugs and other interventions 
on bone health.  Serum osteocalcin is considered a biomarker for bone formation, where 
prednisone decreases serum levels, and this is correlated with bone health outcomes.  
Serum CTX1 (C-terminal telo peptide of Collagen 1) is a marker of bone reabsorption, 
prednisone causes increases in serum levels, and these are also correlated with later bone 
health outcomes.  Osteocalcin and CTX1 serum levels were measured in the Phase I 
MAD groups at the following four time points: Within 2 hours prior to dosing (pre-dose); 

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8 hours postdose day 1 (8 hr); 1 day after 14 days of dosing (14 day); 3 days after last 
dose (Rec) (Table 4, Table 5, Figure 7).  The results showed no significant changes of 
bone turnover markers through the highest vamorolone dose tested compared to placebo 
(20 mg/kg/day vamorolone).  These results are in contrast to prednisone, where two 
independent studies showed significant changes in these same biomarkers at all doses 
tested, to 0.25 mg/kg/day.25,41 
Figure 7 
Comparisons of serum osteocalcin and CTX1 show no differences of 
placebo compared to 20 mg/kg/day vamorolone.  Within 2 hours prior 
to dosing (pre-dose); 8 hours postdose day 1 (8 hr); 1 day after 14 days of 
dosing (14 day); 3 days after last dose (Rec) 
 
 

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Table 4 
Serum osteocalcin concentrations (ng/ml) in vamorolone Phase I MAD 
groups.  Within 2 hours prior to dosing (pre-dose); 8 hours postdose day 1 
(8 hr); 1 day after 14 days of dosing (14 day); 3 days after last dose (Rec) 
Dose vamorolone 
Osteocalcin (ng/ml):  Time Point 
 
Predose 
8 hr 
14 days 
Rec 
Placebo 
46.3 ± 9.7 
40.1 ± 7.4 
40.8 ± 7.9 
38.8 ± 6.2 
1.0 mg/kg 
33.2 ± 11.5 
27.4 ± 9.3 
28.8 ± 9.3 
25.9 ± 8.0 
3.0 mg/kg 
13.7 ± 11.6 
13.6 ± 11.5 
16.1 ± 12.5 
13.9 ± 9.5 
9.0 mg/kg 
32.9 ± 8.6 
20.4 ± 4.7 
26.7 ± 5.2 
33.5 ± 7.2 
20.0 mg/kg 
31.5 ± 6.7 
20.2 ± 4.6 
26.9 ± 4.9 
31.8 ± 5.6 
 
 
Table 5 
Serum CTX1 concentrations (ng/ml) in vamorolone Phase I MAD 
groups.  Within 2 hours prior to dosing (pre-dose); 8 hours postdose day 1 
(8 hr); 1 day after 14 days of dosing (14 day); 3 days after last dose (Rec) 
Dose vamorolone 
CTX1 (ng/ml):  Time Point 
 
Predose 
8 hr 
14 days 
Rec 
Placebo 
0.66 ± 0.12 
0.28 ± 0.05 
0.88 ± 0.22 
0.84 ± 0.22 
1.0 mg/kg 
0.50 ± 0.11 
0.22 ± 0.02 
0.68 ± 0.16 
0.55 ± 0.09 
3.0 mg/kg 
0.31 ± 0.05 
0.18 ± 0.00 
0.48 ± 0.10 
0.46 ± 0.12 
9.0 mg/kg 
0.59 ± 0.11 
0.19 ± 0.006 
0.77 ± 0.13 
0.60 ± 0.10 
20.0 mg/kg 
0.70 ± 0.14 
0.22 ± 0.02 
0.87 ± 0.12 
0.66 ± 0.12 
 
1.3.1.3 
Summary of Phase I data 
In summary: 
• Vamorolone PK data show strong adherence to dose linearity and dose 
proportionality, with relatively little subject-subject variation (both SAD and 
MAD). 
• The half-life was about 2 hours for doses 0.1-1.0 mg/kg.  Doses at 3.0, 8.0, and 
20.0 mg/kg showed an extended tail, increasing half-life to 2.5, 3.8, and 3.8 hours, 
respectively.  The PK for the MAD cohorts was very similar to the SAD cohorts, 
showing little if any drug accumulation, consistent with the short half-life and daily 
dosing schedule. 

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• For the food effect group, a high fat meal was given to a cohort of Phase I SAD 
volunteers with the 8.0 mg/kg dose of vamorolone.  These data were then compared 
to the fasted 8.0 mg/kg cohort data.  The comparison showed that absorption was 
increased by 2.5-fold by the high fat meal, consistent with the lipophilic character 
of vamorolone (steroidal compound). 
• For the MAD cohorts, there were no AEs precluding further escalations in dosing.  
The anticipated therapeutic dose in DMD boys is estimated between 1.0-
8.0 mg/kg/day, and this is the dose range proposed in the later Phase II first-
in-patient studies. 
• Regarding the primary target organ, liver, one subject on placebo in the 1.0 
mg/kg/day cohort and one subject on vamorolone in the 20 mg/kg/day cohort 
showed mild elevations of liver enzymes, and drug dosing was halted.  No subjects 
in the 3.0 or 9.0 mg/kg/day MAD cohorts showed elevations of liver enzymes. 
• Safety PD biomarker studies showed that vamorolone had an improved safety 
window for adrenal axis suppression (100-fold increase in therapeutic window), no 
evidence of insulin resistance, no changes in bone turnover markers (osteocalcin, 
CTX1), compared to prednisone studies reported in the literature.25,41 
The results show that the half-life of vamorolone is similar to glucocorticoids, such as 
prednisone.  Despite the short half-life, prednisone is typically given once per day for 
most indications (including DMD), and once daily dosing is also proposed for 
vamorolone.  Previous studies of increasing the frequency of drug administration of 
glucocorticoids have shown that this has increased side effect profiles without a 
significant gain in efficacy.  Thus, the mechanism of action of glucocorticoids may be 
related to the short-term (pulsed) daily drug exposure.  As vamorolone is thought to share 
a similar anti-inflammatory mechanism of action as glucocorticoids (NF-κB inhibition), 
it is felt that the daily pulsed exposure in the Phase I MAD is most relevant to the planned 
clinical trials in DMD including the Phase II MAD and Phase II efficacy/safety studies, 
where daily dosing schedules will be followed.  The option of increasing the dosing 
regimen in the Phase I MAD to better study drug accumulation and steady state PD was 

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considered, but this was felt to be unrelated to planned Phase II trials, and drug 
mechanism of action. 
1.3.2 
Pharmacokinetics in Phase II Study in 4 to 7 years Duchenne Muscular 
Dystrophy Boys (VBP15-002) 
Preliminary Assessment of Vamorolone (VBP15) Pharmacokinetics in Boys with DMD: 
Pharmacokinetics has been studied in six boys with DMD received 0.25 mg/kg oral doses 
of VBP15 once daily for 14 days.  The drug was administered with milk.  Six blood 
samples were collected at 0, 1, 2, 4, 6, and 8 hours and plasma was analyzed for VBP15.  
The time-course of plasma drug concentrations were assessed using noncompartmental 
(NCA) methods using the WinNonlin software (Certera).  Selected exposure parameters 
from this limited sampling schedule were compared with those from healthy adult men 
from Study VBP15-001, who received a range of single and multiple oral doses of 
VBP15. 
The graphs displayed in Figure 8 depict the plasma concentration versus time profiles for 
all subjects on Days 1 and 14.  The sampling schedule reasonably captured the absorption 
(upcurve) and disposition (downcurve) profiles with peak concentrations occurring at 2 to 
4 hours after dosing.  The Cmax averaged 18.9 (CV% = 46) on Day 1 and 37.9 (42%) 
ng/mL on Day 14.  The Area Under the Curve (AUC) with extrapolation  averaged 87.2 
(37%) on Day 1 and 147.9 (27%) on Day 14.  As the zero-time concentrations of VBP15 
were undetectable before dosing on Day 14 and the half-life of the drug was relatively 
short (5.9 hr on Day 1 and 3.55 hr on Day 14), the increase in concentrations from Day 1 
to Day 14 was not likely due to accumulation.  Increased bioavailability is more likely.  
As the Day 14 exposures are most relevant, a comparison of these plasma concentrations 
with data from adult men will be made. 
 

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Figure 8 
Pharmacokinetics of 0.25 mg/kg/day vamorolone in 4-7 years DMD 
boys 
 
A listing of the NCA pharmacokinetic parameters for the data from Day 14 is provided 
for the 6 subjects in the table.  It should be noted that the clearance values (CL) are 
apparent since the bioavailability of the drug in these subjects is uncertain. 
Table 6 
Pharmacokinetics of 0.25 mg/kg/day vamorolone in 4-7 years DMD 
boys 
 
The PK of VBP15 did not change from Day 1 to Day 14 in healthy men.  The following 
PK metrics were observed in 6 healthy men who received a single dose of 0.3 mg/kg of 
the drug under fasting conditions: 

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Cmax = 50.8 (16.5%); Tmax = 1.5 hr; AUC = 170 (16.5%) ng.hr/mL; t1/2 = 1.60 (17.8%) 
hours; CL/F = 1.76 (15.5%) L/hr/kg. 
It can be observed that most of these metrics are quite comparable between adult men and 
boys with DMD considering that the dose was about 20% lower in the latter group.  
While normal children typically metabolize drugs somewhat faster than adults (clearance 
usually relates to body weight as CL = a.BW**0.75 where “a” is a specific constant for 
each drug), the DMD boys may have somewhat low clearances.   The drug exhibits 
markedly increased absorption when ingested with food in adults.  Thus dosing of the 
drug with milk in the DMD boys may produce increased bioavailability as well and 
produce a higher AUC and lower apparent CL/F.  It can be noted that the mean half-life 
(t1/2) appears much shorter in adults (1.6 hr) than in DMD boys (3.55 hr).  It is likely that 
the longer mean t1/2 is due to prolonged absorption of the drug in 3 subjects as 3 of the 
DMD boys had a more reasonable t1/2 of about 1.5 hours.  It appears that the variability in 
the PK metrics is slighter greater in the DMD boys than in adults.  However, these 
parameters are expected to be more accurate in the adults owing to collection of more 
time samples (n = 13) versus 6 in the DMD boys. 
Conclusion: 
While the increased exposures of the 0.25 mg/kg doses VBP15 taken with milk on 
Day 14 compared to Day 1 are unexpected, the PK metrics observed on Day 14 in DMD 
boys are remarkably consistent with those from adult men who received single fasting 
doses of 0.3 mg/kg.  As VBP15 exhibits linear and consistent pharmacokinetics in adult 
men, increasing the dose in DMD boys should also produce predictably consistent 
increases in exposures. 
1.3.3 
Safety in Phase II Studies in 4 to7 years Duchenne Muscular Dystrophy Boys 
(VBP15-002 and VBP15-003)  
Adverse events: There were no serious adverse events (SAEs) reported over the 14-day 
treatment in the Phase I clinical trial in healthy adult volunteers, nor in the four cohorts 
(0.25 mg/kg, 0.75 mg/kg, 2.0 mg/kg, and 6.0 mg/kg) of the Phase IIa study (VBP15-002; 
14-day treatment) in boys ages 4 to <7 years with DMD.  There has been a total of 

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4 SAEs in the Phase IIa VBP15-003 study and one SAE to date in the VBP15-LTE 
extension study: two SAEs of pneumonia in two different subjects (both subjects 
receiving vamorolone 0.75 mg/kg/day), one SAE of bilateral testicular torsion and one 
SAE of hypoxia in the same subject receiving 6.0 mg/kg/day, and one SAE of influenza 
associated dehydration in a subject receiving 6.0 mg/kg/day.  Each of these SAEs was 
considered unrelated to study drug, and none of them resulted in discontinuation from the 
study.  In the VBP15-003 study, there were a total of 218 TEAEs among 42 of the 48 
subjects (87.5%).  In VBP15-003 study, the TEAEs with the highest incidence were viral 
upper respiratory tract infection (41.7%); pyrexia (35.4%); cough (18.8%); vomiting 
(14.6%); and diarrhea (10.4%).   
Body Mass Index (BMI): Body Mass Index was measured throughout the VBP15-003 
study.  The mean change from baseline to Week 24 for BMI was 0.03, 0.20, 0.23, and 
1.15 for the 0.25, 0.75, 2.0, and 6.0 mg/kg/day dose level groups, respectively.  Body 
Mass Index increases generally reflect an increase in weight.  Body Mass Index z-score 
was monitored in the VBP15-003 study.  The mean change from baseline to Week 24 for 
BMI z-score for the 6.0 mg/kg/day group showed a statistically significant increase 
compared to the mean change from baseline to Week 24 for the 0.25 mg/kg/day and 
0.75 mg/kg/day dose level groups.  In contrast, the mean change from baseline to 
Week 24 for the 2.0 mg/kg/day dose level group in BMI z-score was minimal and 
comparisons with the other vamorolone dose level groups lacked statistical significance.  
The mean increase from baseline to Week 24 for BMI z-score was similar for the 6.0 
mg/kg/day group and a daily prednisone-treated historical control group.   
Potential liver toxicity: In the Phase I clinical trial in adult volunteers, vamorolone 
showed mild elevations of liver enzymes in one subject receiving 20.0 mg/kg in the 
fasted state, and dosing was halted.  All DMD subjects have elevated serum ALT and 
AST enzymes because of the muscle condition.  For that reason, two enzymes, glutamate 
dehydrogenase (GLDH) and gamma glutamyl transferase (GTT), that are preferentially 
expressed in liver were evaluated in the VBP15-003 study.  None of the mean changes in 
GLDH from baseline to any of the VBP15-003 on-treatment assessment time points were 
statistically significant for any dose level group.  Although the mean changes from 

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baseline to Week 8, Week 16, and Week 24 in GLDH levels did not show a dose 
response, shift analysis of GLDH levels did suggest a possible dose-related shift to higher 
GLDH levels at 2.0 mg/kg/day and 6.0 mg/kg/day at Weeks 16 and 24.  Mean GGT 
levels and individual subject values at each VBP15-003 assessment time point across the 
four dose level groups remained at or below the normal range. On the basis of these mean 
GLDH and GGT data, vamorolone at dose levels up to 6.0 mg/kg/day does not appear to 
induce liver toxicity over a 24-week treatment period. 
Adrenal suppression: In the VBP15-003 study, after 24 weeks of treatment, 0 of 8 tested 
participants (0.25 mg/kg/day), 1 of 12 (8.3%) tested participants (0.75 mg/kg/day), 5 of 
12 (41.7%) tested participants (2.0 mg/kg/day), and 8 of 9 (88.9%) tested participants 
(6.0 mg/kg/day) had a depressed morning cortisol (<3.6 μg/dL [100 nM]) consistent with 
chronic adrenal suppression.29 
Insulin resistance: In the VBP15-003 study, mean changes from baseline for fasting 
insulin showed dose-and time-related changes for all dose level groups at Week 12 and 
Week 24.  Statistical significance was observed for mean increase from baseline for the 
6.0 mg/kg/day dose level group at Week 12 and Week 24.  
Bone Turnover: In the VBP15-003 study, pharmacodynamic biomarker testing for bone 
turnover markers suggested that vamorolone does not have the detrimental bone effects 
observed with prednisone and deflazacort. 
1.4 
Rationale for Study Design 
Vamorolone is under development for the treatment of DMD.  The first-in-human clinical 
assessment of vamorolone is ongoing in the SAD/MAD study (VBP15-001) and is 
providing an initial clinical assessment and assessment of the PK characteristics of 
vamorolone following administration of an oral suspension of vamorolone in healthy 
adult subjects.  While there are likely to be some differences between adults and children, 
and between healthy and DMD subjects, the data from VBP15-001 have established the 
2-4 hour half-life of vamorolone, food effect, dose proportionality and variability among 
subjects. 

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A Phase IIa Multiple Ascending Dose study (VBP15-002) will determine the safe and 
tolerable dose(s) of vamorolone to enable future studies with chronic administration in 
DMD subjects, aged 4-7 years.  The narrow age window for this study is driven by 
several factors: 1) the average age of diagnosis is still approximately 4.8 years due to lack 
of screening programs; 2) the current standards of clinical care in Western countries, 
where glucocorticoid therapy is typically initiated between 5 and 7 years of age for DMD 
patients; and 3) the observation that peak function for DMD patients occurs at around 
7 years of age (after which time most affected males with DMD will begin to decline), all 
of which result in a narrow age window to identify steroid-naive males with DMD. 
Key safety parameters in conjunction with PK data are being evaluated during the course 
of the Phase IIa study to assess vamorolone safety and tolerability.  Exploratory clinical 
efficacy parameters and PD biomarkers of tissue breakdown and repair are also being 
evaluated. 
The vamorolone development program has made advances in biomarker discovery and 
development in DMD, with a subset of these studies recently published.42  A panel of 
biomarkers in DMD patient sera that show response to chronic (~4 month) treatment with 
glucocorticoids has been identified.  These chronic prednisone PD biomarkers were 
discovered through study of serum samples of DMD patients enrolled in the Cooperative 
International Neuromuscular Research Group (CINRG) Duchenne Natural History Study 
(DNHS), and data have been reported for the VBP15-002 study.43  SOMAscan aptamer 
panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-
responsive biomarkers, with a subset of these validating in a longitudinal sample set 
(individual DMD patients pre/post steroid treatment).  These PD biomarkers were 
assigned to a safety panel or efficacy panel based on comparison to normal controls and 
information concerning the function of each protein (Table 7).  All safety biomarkers 
were validated in a separate cohort of pediatric inflammatory disease patients 
(longitudinal pre/post steroids).  The same SOMAscan assay was used on the chronic 
samples from the vamorolone Phase IIa trial (entry, 2 weeks treatment, 2 weeks 
washout), with initial data analyses limited to those validated biomarkers shown 
(Table 7). 

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Table 7 
Biomarkers previously defined to be responsive to chronic doses of 
glucocorticoids in DMD boys 
Chronic safety 
Assay method 
Chronic efficacy 
Assay method 
MMP-3  
SOMAscan 
CD23 
SOMAscan 
Leptin  
SOMAscan 
MDC 
SOMAscan 
Insulin  
SOMAscan 
IL-22BP 
SOMAscan 
IGFBP-5  
SOMAscan 
Lymphotoxin a1/b2 
SOMAscan 
Angiotensinogen  
SOMAscan 
IGFBP-2 
SOMAscan 
Afamin 
SOMAscan 
Integrin a1b1; CD49a 
SOMAscan 
17-hydroxyprogesterone 
LC-MS 
MMP-12 
SOMAscan 
Corticosterone 
LC-MS 
 
 
Testosterone 
LC-MS 
 
 
11-deoxycortisol 
LC-MS 
 
 
 
Adrenal axis suppression is a well-documented safety signal with chronic use of 
glucocorticoids.  As noted in Section 1.3.3, in the VBP15-003 study, after 24 weeks of 
treatment, 0 of 8 tested participants (0.25 mg/kg/day), 1 of 12 (8.3%) tested participants 
(0.75 mg/kg/day), 5 of 12 (41.7%) tested participants (2.0 mg/kg/day), and 8 of 9 (88.9%) 
tested participants (6.0 mg/kg/day) had a depressed morning cortisol (<3.6 μg/dL 
[100 nM]) consistent with chronic adrenal suppression.  To further evaluate the effects of 
vamorolone on chronic adrenal axis suppression, four steroid hormones 
(17-hydroxyprogesterone, corticosterone, testosterone, 11-deoxycortisol) are being 
analyzed by LC-MS in the VBP15-LTE study (Table 7).  All four steroid hormones 
showed significant reductions after glucocorticoid treatment in DMD boys in the cross-
sectional and longitudinal CINRG DNHS participants. 
The current long-term extension study (VBP15-LTE) is designed to provide long-term 
safety, efficacy, and PD data for the vamorolone dose(s) that are recognized as safe and 
well-tolerated in the Phase IIa (VBP15-002) and Phase IIa extension (VBP15-003) core 
studies.  Enrollment in this VBP15-LTE long term extension study will be offered to 
subjects who have completed VBP15-003.  VBP15-LTE extends the treatment duration 
and increases the potential for direct benefit of study treatment to these pediatric DMD 
subjects. 

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Subjects enrolling into the VBP15-LTE study will remain on the same dose that they 
were on at the time they completed the Week 24 Final Visit of the VBP15-003 Phase IIa 
extension study (i.e.. one of four doses: 0.25 mg/kg/day, 0.75 mg/kg/day, 2.0 mg/kg/day, 
or 6.0 mg/kg/day).  Subjects, after they have been on their initial dose for at least 1 month 
in VBP15-LTE may be escalated to the next higher dose level at the discretion of the 
Study Chair and Medical Monitor once the next higher dose has been determined to be 
safe in the VBP15-002 Phase IIa Study, and no safety issues with that dose have emerged 
in the VBP15-003 Phase IIa extension study.   
Comparisons of efficacy and safety parameters with historical natural history 
(untreated)44,45,46,47 and prednisone- and deflazacort-treated control groups48 will be 
performed as outcomes of this VBP15-LTE study. 
This trial will be conducted in compliance with this protocol, Good Clinical Practice 
(GCP), applicable Food and Drug Administration (FDA) requirements, and the recently 
issued FDA guidance on developing drugs for treatment for Duchenne muscular 
dystrophy and related dystrophinopathies.49 
It is obligatory that the Investigator become familiar with all sections of the Vamorolone 
Investigator’s Brochure.29 
1.5 
Overall Benefit/Risk 
The current study is a long-term safety and efficacy study in young boys with DMD.  It is 
anticipated that the adverse effect profile of the investigational product will be more 
favorable than standard of care glucocorticoids in the long term (see Section 1.3.3).  The 
adverse effects of vamorolone over long term treatment are not currently known.   
Instructions for detecting adrenal crisis and the circumstances in which stress dose 
steroids should be provided are included in the informed consent form (ICF), and 
Investigators should monitor clinical study participants closely to identify elevations in 
liver-specific enzymes. 
Potential health benefits: Subjects may or may not receive direct health benefit from 
participating in the study.  Subjects will receive vamorolone at one of four planned dose 

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levels (0.25 mg/kg/day, 0.75 mg/kg/day, 2.0 mg/kg/day, or 6.0 mg/kg/day) over the 
course of the 24-week VBP15-003 trial, and then continue on this dose in the current 
VBP15-LTE study for up to 2 years.  As noted above, the Medical Monitor, Study 
Director, and Site Investigator may opt to dose escalate to a higher dose level during the 
VBP15-LTE once the subject has been on the initial dose in VBP15-LTE for at least one 
month, the next higher dose is determined to be safe in the VBP15-002 Phase IIa Study, 
and no safety issues with that dose have emerged in the VBP15-003 Phase IIa extension 
study.  In the VBP15-003 study, clinical efficacy was assessed by Timed Function Tests.  
Improvement in Time to Stand, Time to Climb, Time to Run/Walk 10 Meters, and 
6-Minute Walk Test were seen predominantly for the 2.0 and 6.0 mg/kg/day dose level 
groups, with many of the improvements showing statistical significance compared to an 
untreated Duchenne Natural History Group.  In view of the initial clinical evidence of 
safety, the improvements seen in assessments of efficacy, and the monitorable nature of 
key potential adverse effects, , data support an acceptable benefit/risk profile for 
vamorolone. 
2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Study Objectives 
2.1.1 
Primary Objectives 
The primary objectives of this study are: 
1. To evaluate the long-term safety and tolerability of vamorolone, administered 
orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period, in young 
boys with DMD who completed protocol VBP15-003; and 
2. To compare the efficacy, as measured by the Time to Stand Test (TTSTAND), of 
vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month 
Treatment Period vs. untreated DMD historical controls in young boys with 
DMD. 
2.1.2 
Secondary Objectives 
The secondary objectives of this study are: 

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1. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on serum pharmacodynamic (PD) 
biomarkers of safety (insulin resistance, adrenal axis suppression, and bone 
turnover);  
2. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period, on muscle strength, mobility and 
functional exercise capacity vs. untreated DMD historical controls as measured by 
Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment (NSAA), 
Time to Climb Test (TTCLIMB), 6-minute Walk Test (6MWT), and Quantitative 
Muscle Testing (QMT) in young boys with DMD; and 
3. To compare the safety, as assessed by bone age, spine fractures, BMI z-score, and 
height z-score, of vamorolone administered orally at daily doses up to 6.0 mg/kg 
over a 24-month Treatment Period vs. prednisone- and deflazacort-treated 
historical control boys with DMD. 
2.1.3 
Exploratory Objectives 
The exploratory objectives of this study are: 
1. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on Quality of Life measures 
(Pediatric Outcomes Data Collection Instrument [PODCI]); 
2. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on additional exploratory PD 
biomarkers; and 
3. To determine if established genetic modifiers of DMD (gene polymorphisms 
associated with disease severity, or response to glucocorticoid treatment) are 
similarly associated with vamorolone-treated DMD patients (baseline disease 
severity, or response to vamorolone treatment). 

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2.2 
Study Endpoints 
2.2.1 
Safety Endpoints 
1. BMI z-score: Comparison with prednisone- and deflazacort-treated historical 
control groups for change from Baseline to Month 12 and Month 24; 
2. BMI z-score: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points; 
3. Height z-score: Comparison with prednisone- and deflazacort-treated historical 
control groups for change from Baseline to Month 12 and Month 24; 
4. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 
by system organ class (SOC): Overall by treatment, by treatment and relationship, 
and by treatment and intensity (see Section 7.2.6); 
5. Vital signs [blood pressure, heart rate, respiratory rate, oral body temperature]: 
Change from Baseline to each of the scheduled on-treatment and post-treatment 
assessment time points; 
6. Body weight: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points; 
7. Clinical laboratory values (hematology and biochemistry): Change from Baseline 
to each of the scheduled on-treatment and post-treatment assessment time points; 
8. Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high 
density lipoprotein [HDL]):  Change from Baseline to each of the scheduled on-
treatment and post-treatment assessment time points; 
9. Urinalysis by dipstick and microscopic analysis: Change from Baseline to each of 
the scheduled on-treatment and post-treatment assessment time points; 
10. 12-lead electrocardiogram (ECG): Change from Baseline to each of the scheduled 
on-treatment and post-treatment assessment time points; 
11. Hand x-ray: bone age at Month 24; 
12. Spine x-ray: Spine fractures at Month 24. 

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Data for the following additional safety outcomes will be listed only: 
1. Physical examination findings at Pretreatment, Month 12, and Month 24. 
2.2.2 
Clinical Efficacy Endpoints 
2.2.2.1 
Primary Clinical Efficacy Endpoint 
1. Time to Stand Test (TTSTAND) velocity (rise/second):  Comparison with a 
historical natural history (untreated) control group for change from Baseline to 
Month 24. 
2.2.2.2 
Secondary Efficacy Endpoints 
1. Time to Stand Test (TTSTAND) velocity (rise/second):  Comparison with a 
historical natural history (untreated) control group for change from Baseline to 
Month 12; 
2. Time to Stand Test (TTSTAND):  Change from Baseline to each of the scheduled 
on-treatment and post-treatment assessment time points; 
3. Time to Climb (4 Steps) Test (TTCLIMB): Change from Baseline to each of the 
scheduled on-treatment and post-treatment assessment time points; 
4. 
North Star Ambulatory Assessment (NSAA):  Change in timed assessments and 
total score from Baseline to each of the scheduled on-treatment and post-
treatment assessment time points; 
5. 
Total distance traveled, in meters, in completing the Six-minute Walk Test 
(6MWT):  Change from Baseline to each of the scheduled on-treatment and post-
treatment assessment time points;  
6. 
Time to Run/Walk Test (TTRW):  Change from Baseline to each of the 
scheduled on-treatment and post-treatment assessment time points; and 
7. 
Quantitative Muscle Testing (QMT): Change from Baseline to each of the 
scheduled on-treatment and post-treatment assessment time points. 

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2.2.3 
Pharmacodynamic Endpoints 
Concentrations of serum PD biomarkers of adrenal suppression, insulin resistance, and 
bone turnover. 
2.2.4 
Exploratory Endpoints 
1. Pediatric Outcomes Data Collection Instrument (PODCI): Change from baseline 
to each of the scheduled on-treatment and post-treatment assessment time points; 
2. Levels of additional exploratory PD biomarkers; and 
3. DNA testing for established genetic modifiers of DMD. 
2.2.5 
Endpoints for Subject Reported Outcomes 
Safety endpoints based on subject reports of AEs are listed in Section 2.2.1.  
Additionally, subjects’ parents/legal guardians will be asked to complete the Pediatric 
Outcomes Data Collection Instrument (see Section 7.3.8).  No other subject-reported 
outcomes are planned. 
3 
STUDY DESIGN 
3.1 
Overall Study Design 
This Phase II long term extension study is an open-label, multiple-dose study to evaluate 
the long-term safety, tolerability, efficacy and PD of vamorolone administered once daily 
by liquid oral suspension over a Treatment Period of 24 months to young boys with 
DMD. 
Only subjects who have completed the VBP15-003 Phase IIa extension study Week 24 
Final Visit will be eligible for participation in the VBP15-LTE open-label extension 
study.  Participation in this extension study will be discussed with the subject’s parent or 
guardian prior to the subject’s final visit of VBP15-003.  A total of up to approximately 
50 subjects will be enrolled into this long term extension study. 
The parents or legal guardians of subjects who choose to enroll in this long term 
extension study will give written informed consent for the long-term extension study at 
the VBP15-LTE Baseline Day -1 Visit.  The Baseline Day -1 Visit, including signing of 

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the VBP15-LTE-specific ICF, may occur at the conclusion of the VBP15-003 final visit; 
alternatively, the Baseline Day -1 Visit and VBP15-003-specific ICF signing may occur 
up to 8 weeks after the final VBP15-003 visit for subjects who dose taper, at the 
convenience of the subject’s parent or legal guardian and discretion of the Investigator.  
Subjects are considered to be enrolled in the VBP15-LTE long term extension study after 
the parent or guardian has signed the VBP15-LTE-specific ICF.  Each subject will retain 
the study identification number assigned to him at the start of the Phase IIa study 
VBP15-002 and retained in the Phase IIa extension study VBP15-003. 
For subjects who enroll in the VBP15-LTE long term extension study within 28 days 
after completion of all VBP15-003 Week 24 final assessments, many of the safety, 
efficacy, and PD assessments performed at the VBP15-003 Week 24 Final Visit may be 
used to determine extension study eligibility and/or to provide baseline study data for the 
extension study and do not need to be repeated at the VBP15-LTE Baseline Day -1 Visit 
(see Table 8).  For these subjects, additional long term extension study procedures will 
still be performed at the Baseline Day -1 Visit, within 24 hours prior to administration of 
the first dose of study drug in the long term extension study.  Subjects who enroll in the 
VBP15-LTE long term extension study > 28 days after the date of the VBP15-003 Week 
24 Final Visit must have all Baseline Day -1 assessments performed, according to the 
schedule in Table 8. 
Subjects in the VBP-LTE will begin dosing at the same vamorolone dose level they 
received at the time they completed the Week 24 Final Visit in the VBP15-003 Phase IIa 
extension core study.  Subjects, once they have been on their initial dose in the 
VBP15-LTE study for at least one month, may have their dose escalated at the discretion 
of the Study Chair and Medical Monitor once that dose has been determined to be safe in 
the VBP15-002 Phase IIa Study, and no safety issues have emerged at that dose in the 
VBP15-003 Phase IIa extension study.  Subjects may continue to have their dose of study 
medication escalated incrementally at no shorter than one-month intervals to the 
maximum dose tested and assessed as safe in the VBP15-002 and VBP15-003 studies, 
6.0 mg/kg/day.  Subjects will continue to receive vamorolone at one of the assigned dose 

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levels for the duration of the 24-month Treatment Period, unless ongoing safety data 
indicate the dose level should be de-escalated. 
If dose limiting toxicities are identified in the VBP15-002 Phase IIa study or VBP15-003 
Phase IIa extension study which preclude confirmation of safety of all four planned dose 
levels, the dose levels in this extension study will be modified, as needed. 
In the event any clinical observation suggests an intolerability for an individual subject to 
the study medication, in the opinion of the Investigator, the subject’s dose level may be 
decreased to the next lower dose level and maintained at that lower dose level throughout 
the duration of the Treatment Period, with the caveat stated below for subjects 
de-escalating from 6.0 mg/kg/day to 2.0 mg/kg/day.  In the event the next lower dose 
level is also not tolerated and is considered a safety risk to the subject, in the opinion of 
the Investigator, Study Chair, and Medical Monitor, the subject should be withdrawn 
from the study.  Subjects whose dose is decreased from 6.0 mg/kg/day to 2.0 mg/kg/day 
may have their dose subsequently increased to 4.0 mg/kg/day if they have been taking the 
2.0 mg/kg/day dose for at least one month and, in the opinion of the Investigator, 
balancing efficacy with safety concerns, they could benefit from an intermediate higher 
dose.  Details of dose interruption, de-escalation, and discontinuation are presented in 
Section 5.6. 
Subjects will be assessed for safety and tolerability, clinical efficacy, and PD at 
scheduled visits throughout the 24-month Treatment Period (see Table 8 for a schedule 
of study assessments).  Treatment Period study visits will occur at Month 1, Month 3, and 
every 3 months thereafter through Month 24 (Table 8).  Adverse events, including SAEs, 
and concomitant medications will be recorded throughout the study. 
Once daily Treatment Period study drug dosing will occur from Day 1 until the Month 24 
Visit (Section 5.3). 
Subject diaries will be dispensed at Baseline Day -1 and at each subsequent 3-month 
scheduled study visit to record AEs and changes to concomitant medications taken during 
the study. 

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All subjects will return to the clinical site for Month 24 assessments.  Subjects who 
switch to standard of care glucocorticoids for DMD or who discontinue treatment will 
participate in a Dose-tapering Period of 2-5 weeks in duration, following the end of the 
Treatment Period and prior to discharge from the study (see Section 6.3.4).  Subjects will 
be discharged from the study following completion of all final Month 24 or 
Dose-tapering Period assessments, as appropriate. 
In the event that any clinical or laboratory parameters remain abnormal at the time of 
discharge from the study, the subject will be followed medically as clinically indicated.  
Any subject who discontinues the study prior to the Month 24 Visit should return to the 
study unit for final Month 24 safety and efficacy assessments at the time of early 
discontinuation. 
3.2 
Study Summary 
This Phase II long term extension study is an open-label, multicenter study to evaluate 
the long-term safety, tolerability, clinical efficacy, and PD of vamorolone at dose levels 
up to 6.0 mg/kg administered daily by liquid oral suspension over a Treatment Period of 
24 months to young boys with DMD who participated in the VBP15-002 Phase IIa and 
VBP15-003 Phase IIa extension core studies. 
The study is comprised of a Pretreatment Baseline Period of up to 24 hours in duration, 
which begins at the signing of the VBP-LTE study-specific informed consent, a 
24-month Treatment Period, and a 2- to 5-week Dose-tapering Period for subjects who 
elect to transition off vamorolone treatment at the end of the study. 
4 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS 
4.1 
Subject Screening, Enrollment, and Identification Log 
All subjects who complete the Week 24 Final Visit of the VBP15-003 Phase IIa core 
extension study will be eligible for enrollment in this VBP15-LTE long term extension 
study, provided they meet all VBP15-LTE study entry criteria.  Limited data will be 
collected for subjects who are not interested in participating in the study, including date 
of birth and reason for exclusion from the study.  Subjects are considered to be enrolled 

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in the VBP15-LTE long term extension study after the parent or guardian has signed the 
VBP15-LTE-specific ICF at the Baseline Day -1 Visit.  The Baseline Day -1 Visit, 
including signing of the ICF, may occur at the conclusion of the final visit of the VBP15-
003; alternatively, the Baseline Day -1 Visit and VBP15-LTE-specific ICF signing may 
occur up to 8 weeks after the VBP15-003 final visit following dose-tapering, at the 
convenience of the subject’s parent or legal guardian and discretion of the Investigator. 
Subject enrollment and identification logs will be maintained for all subjects enrolled in 
the study.  These logs will be reviewed during routine monitoring calls and/or visits. 
4.2 
Inclusion Criteria 
To qualify for enrollment in this extension study, the subject must satisfy the following 
inclusion criteria: 
1. Subject’s parent or legal guardian has provided written informed consent and 
HIPAA authorization (if applicable) prior to any VBP15-LTE long-term 
extension study-specific procedures; 
2. Subject has previously completed study VBP15-003 up to and including the 
Week 24 Final assessments prior to enrolling in the VBP15-LTE study at the 
conclusion of the VBP15-003 Week 24 Visit [Note: if entering the dose-tapering 
period, subject is enrolling within 8 weeks after the VBP15-003 final visit 
following dose-tapering]; and 
3. Subject and parent/guardian are willing and able to comply with scheduled visits, 
study drug administration plan, and study procedures. 
4.3 
Exclusion Criteria 
A subject will be excluded from enrollment in this extension study if he meets any of the 
following exclusion criteria: 
1. Subject had a serious or severe adverse event in study VBP15-003, that, in the 
opinion of the Investigator, was probably or definitely related to vamorolone use 
and precludes safe use of vamorolone for the subject in this long-term extension 
study; 

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2. Subject has current or history of major renal or hepatic impairment, diabetes 
mellitus or immunosuppression; 
3. Subject has current or history of chronic systemic fungal or viral infections; 
4. Subject has used mineralocorticoid receptor agents, such as spironolactone, 
eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), 
mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study 
medication; 
5. Subject has evidence of symptomatic cardiomyopathy.  [Note: Asymptomatic 
cardiac abnormality on investigation would not be exclusionary]; 
6. Subject is currently being treated or has received previous treatment with oral 
glucocorticoids or other immunosuppressive agents.  [Notes: Past transient use of 
oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 
months cumulative, with last use at least 3 months prior to first dose of study 
medication, will be considered for eligibility on a case-by-case basis.  Inhaled 
and/or topical glucocorticoids prescribed for an indication other than DMD are 
permitted but must be administered at stable dose for at least 3 months prior to 
study drug administration]; 
7. Subject has used idebenone within 4 weeks prior to the first dose of study 
medication; 
8. Subject has an allergy or hypersensitivity to the study medication or to any of its 
constituents; 
9. Subject has severe behavioral or cognitive problems that preclude participation in 
the study, in the opinion of the Investigator; 
10. Subject has previous or ongoing medical condition, medical history, physical 
findings or laboratory abnormalities that could affect safety, make it unlikely that 
treatment and follow-up will be correctly completed or impair the assessment of 
study results, in the opinion of the Investigator; or 

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11. Subject is currently taking any investigational drug, or has taken any 
investigational drug other than vamorolone within 3 months prior to the start of 
study treatment. 
Note: Subjects may be re-evaluated if ineligible due to a transient condition which 
would prevent the subject from participating. 
4.4 
Withdrawal of Subjects from Study 
A subject may withdraw from the study, or may be withdrawn by his parent or guardian 
at any time without the need to justify the decision. 
The Investigator has the right to terminate participation of a subject in the study for any 
of the following reasons: 
• The subject’s parent/legal guardian is uncooperative/noncompliant and does not 
adhere to study responsibilities, including failure to appear at study visits; 
• Difficulty in obtaining blood samples from the subject for safety monitoring; 
• The subject experiences an unmanageable or non-tolerable AE/SAE which is 
considered to be possibly, probably, or definitely related to study drug, in the 
opinion of the Investigator; 
• The Sponsor terminates the study; 
• Any other reason relating to subject safety or integrity of the study data. 
In the event a subject is withdrawn from the study, the Sponsor or designee (e.g., 
Coordinating Center) will be informed within one business day.  If there is a medical 
reason for withdrawal, the subject will remain under the supervision of the Investigator 
until resolution of the event. 
All subjects who withdraw from the study prior to the Month 24 Visit should return to 
the study site for Month 24 assessments at the time of early withdrawal, assuming the 
subject has not withdrawn consent.  In the event a subject withdraws informed 
consent, no further study procedures should be performed and no additional data 

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should be collected.  Any data collected up to the point of withdrawal of informed 
consent may be used by the Sponsor. 
4.5 
Replacement of Withdrawn Subjects 
Only subjects who have completed the VBP15-003 Phase IIa extension study are eligible 
to enroll in this long-term extension study.  Subjects prematurely discontinued from the 
VBP15-LTE long term extension study will not be replaced. 
4.6 
Termination of Study 
This study may be prematurely terminated if, in the opinion of the Sponsor, there is 
sufficient reasonable cause.  An example of a circumstance that may warrant termination 
is determination of unexpected, significant, or unacceptable risks to participants. 
If the study is prematurely terminated or suspended, the Sponsor will promptly inform the 
site Investigators and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension.  The Institutional Review Board(s) 
(IRB[s])/Independent Ethics Committee(s) (IEC[s]) will also be informed promptly by 
the Investigator/institution or the Sponsor and provided the reason(s) for the termination 
or suspension. 
Subject enrollment at a given site may be terminated by the Sponsor.  Possible reasons 
for termination of the study at a given site include, but are not limited to: 
1.  Unsatisfactory enrollment with respect to quantity or quality 
2.  Inaccurate or incomplete data collection 
3.  Falsification of records 
4.  Failure to adhere to the protocol. 
5 
TREATMENT OF STUDY SUBJECTS 
5.1 
Study Medication Administered 
Vamorolone will be administered to all subjects as an oral liquid suspension. 
Planned vamorolone dose levels: 0.25 mg/kg, 0.75 mg/kg/day, 2.0 mg/kg, and 6.0 mg/kg. 

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Vamorolone will be administered to all subjects once daily for 24 months, from Study 
Day 1 until the Month 24 Visit.  At the end of the 24-month Treatment Period, a subset of 
subjects may receive additional vamorolone treatment in a dose-tapering manner during a 
2- to 5-week Dose-tapering Period, prior to discharge from the study (see Section 6.3.4). 
5.2 
Identity of Investigational Product 
ReveraGen BioPharma, Inc. will supply the following investigational study medication: 
Name: 
Vamorolone 
Active Substance: 
VBP15 
Strength: 
4% by weight 
Dosage Form: 
Oral suspension 
Manufacturer: 
Velesco Pharma 
5.3 
Dosage Schedule and Administration of Study Medication 
Subjects who have completed the Phase IIa extension VBP15-003 study and who meet all 
other eligibility criteria (see Sections 4.2 and 4.3) will be enrolled into this long term 
extension study on Baseline Day -1, following signing of the VBP15-LTE extension-
study-specific ICF.  Subjects will retain the enrollment numbers assigned to them for the 
Phase IIa extension VBP15-003 core study. 
Subjects will receive vamorolone 0.25 mg/kg, 0.75 mg/kg/day, 2.0 mg/kg, or 6.0 mg/kg, 
administered orally once daily with a glass of full fat milk (approximately 8 grams of fat) 
or food with similar fat content of the subject’s choice from Study Day 1 to Month 24.  A 
subset of subjects may also receive vamorolone for an additional 1-4 weeks according to 
a dose-tapering protocol following the end of the Treatment Period (see Section 6.3.4). 
The site pharmacist or designated site study staff will dispense study medication in 
100 mL bottles to each subject enrolled in the study (see Section 5.8.1 and Appendix 
14.1).  All subjects will receive vamorolone 4% oral suspension.   
Study medication sufficient for 3 months of daily dosing (plus overage) will be dispensed 
by trained study staff on Study Day -1 and at each scheduled subsequent 3-month visit 
thereafter.  Each subject’s dose (in mg and mL) will be calculated based on the weight of 

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the subject (in kg) recorded at the dispensing visit (see Appendix 14.1 for a dose 
calculation worksheet). 
Enrolled subjects will receive all doses of vamorolone under the supervision of parent or 
legal guardian or trained study staff.  Dosing is to occur at home throughout the 24-month 
Treatment Period, except at the Month 9 and Month 21 Visits when dosing will occur at 
the study site to accommodate morning fasted blood collections.  Study drug will be 
administered by mouth using a volumetric syringe supplied by the site.  Following 
administration of the dose of study drug, the syringe will be filled once with water and 
the water will be administered by mouth using the volumetric syringe.  The subject will 
then drink approximately 50 mL of water to ensure the full dose has been ingested.  
Subjects should receive each dose of study medication at approximately the same time of 
day. 
The daily dose of study medication should be taken with a full glass of whole milk 
(approximately 8 grams of fat), or equivalent high fat food portion. 
The dispensed study medication bottle(s) will be returned to the study site at each 
subsequent scheduled visit. 
5.4 
Rationale for Dose Selection 
Dose levels were chosen for this study to ensure the safety of subjects enrolled in the 
study, to allow demonstration of efficacy and PD effects, and to ensure adequate safety in 
future clinical studies and in the patient population after FDA regulatory approval.  All 
dosing will be done in the morning with a glass of whole milk (approximately 8 grams of 
fat) or similar fat equivalent meal. 
Each subject will enroll in this long-term extension study to receive the same dose that he 
received at the time the subject completed the Week 24 Visit of the VBP15-003 core 
study.  The planned dose levels in this study are 0.25 mg/kg, 0.75 mg/kg, 2.0 mg/kg, and 
6.0 mg/kg.  If dose-limiting toxicities are observed in the Phase IIa or Phase IIa extension 
core studies at doses being used in this LTE study, dose level(s) will be de-escalated, as 
appropriate. 

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Based on the safety data presented in Section 1.3.3, the doses initially selected for this 
study are appropriate for evaluation in a long-term extension study. 
5.5 
Treatment Compliance 
Subject compliance with the dosing schedule will be assessed by site maintenance of 
accurate study drug dispensing and return records.  The Investigator is responsible for 
ensuring that dosing is administered in compliance with the protocol.  The Investigator or 
designee will instruct the subject’s parent or guardian with regard to proper dosing of 
study medication, and will reinforce the importance of taking all study medication per 
protocol instructions.  The volume of unused study medication remaining in each bottle 
returned will be documented in the source documents and on the appropriate electronic 
case report form (eCRF). 
5.6 
Study Drug Dose Interruption, De-escalation, or Discontinuation 
Administration of study drug to individual subjects should be interrupted, and the case 
discussed with the Study Chair and Medical Monitor within 24 hours, in the event any 
clinical observation suggests an intolerability to the study medication and a safety risk to 
an individual subject, in the opinion of the Investigator.  In such an event, or in situations 
where the intolerability is not considered an immediate safety risk to the subject, the 
subject’s dose level may be decreased to the next lower dose level and maintained at that 
lower dose level throughout the duration of the study, with the caveat stated below for 
subjects de-escalating from 6.0 mg/kg/day to 2.0 mg/kg/day.  In the event the next lower 
dose level is also not tolerated and is considered a safety risk to the subject, in the opinion 
of the Investigator, Study Chair and Medical Monitor, the subject should be withdrawn 
from the study. 
Subjects whose dose is decreased from 6.0 mg/kg/day to 2.0 kg/kg/day may have their 
dose subsequently increased to 4.0 mg/kg/day if they have been taking the 2.0 mg/kg/day 
dose for at least one month and, in the opinion of the Investigator, balancing efficacy 
with safety concerns, they could benefit from an intermediate higher dose.   
In the event that dose-limiting toxicities are observed in the VBP15-002 Phase IIa or 
VBP15-003 Phase IIa extension study that require de-escalation of dose in the long-term 

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extension study VBP15-LTE, subjects will be de-escalated as dictated by safety results in 
the VBP15-003 study. 
5.7 
Prior and Concomitant Medications and Therapies 
5.7.1 
Prior Therapy 
Any changes in non-study medication/therapy, including administration of new 
medication(s), change of dose, or discontinuation of medication, that occur after 
completion of the VBP15-003 core study Week 24 final assessments, or the final 
assessments following dose-tapering for subjects who taper the dose, and prior to 
administration of the first dose of study medication in the extension study will be 
captured as prior medications (Medication History) in the VBP15-LTE extension study 
eCRF. 
5.7.2 
Concomitant Therapy 
Any medications that are started after administration of the first dose of study medication 
in the VBP-15 LTE extension study will be recorded as concomitant medications on the 
appropriate eCRF.  Subject diaries will be provided to subjects to record any concomitant 
medication changes during the study (see Section 8.4). 
All medications (prescription and over-the-counter [OTC]) taken during the VBP15-LTE 
study must be recorded in the source documents and in the eCRF, including the name of 
the medication, dosage and regimen, reason for therapy, and treatment start and stop 
dates.  Furthermore, each change in concomitant medication (e.g., new treatment, 
discontinuation of treatment, or change in dosage/regimen) during the study must be 
documented in the same manner.  Details of any non-pharmacological therapies (e.g., 
devices, procedures), including name, reason for therapy, and dates of therapy, will also 
be recorded.  Site personnel will review the information with the subject and/or his parent 
or guardian, if applicable, for completeness and accuracy at each study visit. 

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5.7.3 
Prohibited Therapies 
Subjects must discontinue use of the following medications prior to participation in the 
study, as indicated, and refrain from using these medications throughout the duration of 
the study: 
• Mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone 
(canrenoate potassium), prorenone (prorenoate potassium), mexrenone 
(mexrenoate potassium): use must be discontinued at least 4 weeks prior to the 
first dose of study medication; 
• Oral glucocorticoids or other oral immunosuppressive agents:  Subjects who have 
received more than 3 months cumulative treatment with oral immunosuppressive 
agents or last treatment within 3 months prior to first dose of study medication are 
ineligible for study entry.  [Note: Inhaled and/or topical glucocorticoids 
prescribed for an indication other than DMD are permitted but must be 
administered at stable dose for at least 3 months prior to study drug 
administration]; 
• Idebenone: use must be discontinued at least 4 weeks prior to first dose of study 
medication; 
• Live attenuated vaccines (use must be avoided for the duration of participation in 
the study); 
• Medications indicated for the treatment of DMD, including Exondys 51 and 
Translarna (use must be avoided for the duration of participation in the study); 
• Any investigational medications other than vamorolone (use must be discontinued 
at least 3 months prior to the first dose of study medication). 
The Investigator should contact the Study Chair concerning individual medications or 
therapies not listed that may be of concern. 

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5.7.4 
Permitted Therapies 
Every effort should be made NOT to take any prescription or OTC medications during 
the study.  Concomitant medications should be maintained on the same dose and regimen 
throughout the study whenever possible.  However, all other medications other than those 
specifically prohibited above may be taken during the study, if clinically indicated, 
provided they are recorded in the source documents and in the eCRF. 
5.8 
Study Medication Management 
5.8.1 
Packaging and Labeling of Study Medication 
The site pharmacist or designated study staff will receive clinical trial material (CTM) 
when all regulatory requirements have been completed by the site.  Additional CTM will 
be available upon request.  ReveraGen BioPharma, Inc. or designee will provide CTM in 
bulk quantities sufficient to satisfy the protocol requirement.  Clinical trial material will 
be shipped in bulk to the study site’s registered pharmacist or designated study staff in 
suitably labeled study cartons.  Cartons will contain study medication packaged in sterile 
100 mL glass bottles; each bottle will contain 4 grams of vamorolone as a 4% suspension 
in sterile water.  Bulk drug supplies will be labeled with the name of Sponsor, protocol 
number, lot number, expiration or retest date, and other appropriate study information.  
Bottle labels will include the following statement: “Caution: New Drug – Limited by 
Federal Law to Investigational Use” or comparable statement, as required by ex-US 
regulatory authorities. 
100 mL bottles of 4% vamorolone oral suspension will be dispensed to the subject’s 
parent or legal guardian at the Baseline Day -1 Visit and at each scheduled dispensing 
visit (see Appendix 14.1 for instructions on calculating the number of vamorolone 
bottles to be dispensed at Baseline Day -1 and each subsequent scheduled 3-month visit); 
dispensed bottle(s) of study medication will be returned at each subsequent scheduled 
3-month visit, prior to dispensing sufficient bottle(s) to provide daily dosing until the next 
subsequent scheduled 3-month visit.  Each vamorolone study medication bottle may be 
used for a single subject only.  The volume per dose to be administered to each subject 
depends on the subject weight calculated at the dispensing visit; see Appendix 14.1 for 

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complete instructions on calculating dose volume.  Clinical supplies dispensed by the 
study site staff and ready for administration to subjects will be labeled with the dispense 
date, protocol number, vamorolone dose level, and volume to be administered per dose. 
5.8.2 
Storage of Study Medication 
All CTM for use in the trial must be stored in a locked container/cabinet free from 
environmental extremes, under the responsibility of the institutional pharmacist or 
Principal Investigator.  Bulk study medication should be stored at refrigerated 
temperature (2oC – 8oC; 36oF – 46oF).  Excursions to ambient temperature are allowed.  
Access to study medication stored at the study site must be limited to authorized clinic 
personnel. 
5.8.3 
Study Medication Shipping and Handling 
Clinical trial material will be shipped to the study sites only after receipt of required 
documents in accordance with applicable regulatory requirements and Sponsor 
procedures. 
Clinical trial material will only be dispensed once a subject has (1) a signed ICF and 
HIPAA authorization, if applicable, on file, and has been enrolled in the VBP15-LTE 
long-term extension study; (2) met all eligibility criteria for entry into the VBP15-LTE 
long-term extension study, (3) completed all Pretreatment requirements. 
It is essential to this study that all CTM be accounted for during the study period.  All 
unused study medication will be retained at the study site for reconciliation and collection 
by the Sponsor's study monitors (or designees) during routine monitoring visits.  Study 
site personnel should not dispose of any CTM.  Final disposition of all unused CTM will 
be coordinated by the Sponsor's study monitors (or designees) at the end of the study (see 
Section 5.8.4). 
Clinical trial material must be dispensed and administered according to the procedures 
described in this protocol.  Only subjects enrolled in the study may receive study 
medication, in accordance with all applicable regulatory requirements.  Only authorized 
study personnel may supply CTM.  Authorized study personnel refers to the Investigator 

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(or designee), in accordance with all applicable regulatory requirements and the Site 
Signature Log/Delegation of Authority.  Only authorized study personnel or the subject’s 
parent or legal guardian may administer CTM. 
5.8.4 
Study Medication Accountability 
The Investigator is responsible for the control of drugs under investigation.  Adequate 
records of the receipt (e.g., Drug Receipt Record) and disposition (e.g., Drug Dispensing 
Log) of the study drug must be maintained.  The Drug Dispensing Log must be kept 
current and should contain the following information: 
• The identification of the subject to whom the study drug was dispensed 
• The date(s) and quantity of the study drug dispensed to the subject 
• The date(s) and quantity of the study drug returned by the subject. 
All records and drug supplies must be available for inspection by the Study Monitor at 
every monitoring visit.  Unused medication will be returned to ReveraGen or its designee 
at the end of the study.  The completed Drug Dispensing Log and drug return record(s) 
will be returned to ReveraGen or its designee.  The Investigator’s copy of the drug return 
record(s) must accurately document the return of all study drug supplies to ReveraGen or 
its designee. 
5.9 
Procedures for Assigning Subject Study Numbers 
This is an open-label study.  Subjects enrolled in this long-term extension study will 
retain the enrollment numbers assigned to them at the start of the VBP15-002 core study.  
All data for all subjects whose parent or guardian signs the ICF for the VBP15-LTE 
extension study will be identified using the unique subject identification number.  
Subjects are considered to be enrolled in this extension study when the parent or guardian 
signs the VBP15-LTE extension study-specific ICF at the Baseline Day -1 Visit.  The 
Site Investigator will keep a record relating the names of the subjects to their enrollment 
numbers (Subject Identification Log) to permit efficient verification of data subject files, 
when required.  This record will also include the dates of subject enrollment and 
completion/termination. 

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6 
STUDY SCHEDULE 
6.1 
Time and Events Schedule 
The study procedures to be conducted for each subject are divided into the following 
study periods:  
Pretreatment Baseline Period:  The 24-hour period immediately prior to administration 
of the first dose of study medication (Study Day -1), which includes signing of the 
VBP15-LTE extension study-specific ICF and HIPAA authorization, if applicable, and 
enrollment into the extension study.  The Baseline Day -1 Visit will generally coincide 
with the final Week 24 Visit in the VBP15-003 core study.  Alternatively, subjects who 
participate in the Dose-tapering Period may return to the study site up to 8 weeks after 
completion of the VBP15-003 final assessments following the Dose-tapering Period for 
signing of the ICF and HIPAA authorization, if applicable, and completion of Baseline 
assessments at Baseline Day -1. 
Treatment Period:  The 24-month interval starting with administration of the first dose 
of study medication on Study Day 1and continuing through the time of the Month 24 
Visit and administration of the final dose of Treatment Period study medication. 
Dose-tapering Period:  The 2- to 5-week interval following the end of the 24-month 
Treatment Period during which subjects who elect to either switch to standard of care 
glucocorticoids for DMD, or discontinue vamorolone and not begin standard of care 
glucocorticoid treatment, at the end of the study will have their vamorolone dose tapered 
to 0 mg/kg/day.  The length of time required for this tapering will depend upon the dose 
received during the Treatment Period (see Section 6.3.4).  Subjects whose dose is tapered 
during the Dose-tapering Period will be discharged from the study following completion 
of all final Dose-tapering Period assessments. 
The procedures to be completed during each study period are presented in the Schedule 
of Study Assessments in Table 8 and in the sections that follow.  Detailed descriptions of 
the assessments and the definitions of study endpoints are provided in Section 7 and 
Section 2.2.  Any deviation from study procedures should be noted in the source 

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documents and in the eCRF, and significant deviations should be reported immediately to 
the Sponsor. 
Overall, approximately 24-25 months are allocated for each subject to complete the 
study, including a 1-day Pretreatment Baseline Period and a 24-month Treatment Period 
for all subjects.  For subjects who elect to either switch to standard of care 
glucocorticoids for DMD, or discontinue vamorolone and not begin glucocorticoid 
treatment at the end of the study, an additional 2-5 weeks are allocated for vamorolone 
dose tapering and final study assessments. 
 

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Table 8 
Schedule of Study Activities 
Pretreatment Period 
Treatment Period 
Dose-
tapering 
Period 
Baseline 
 
Day 
Month 
Study Day or Month/Visit 
-1a 
1b 
1 
(±7d) 
3 
(±7d) 
6 
(±7d) 
9 
(±7d) 
12 
(±7d) 
15 
(±7d) 
18 
(±7d) 
21 
(±7d) 
24c 
(±7d) 
24-25d 
(±7d) 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
Xe 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
X 
 
 
 
 
 
 
 
 
 
 
 
Interim Medical History 
Xf 
 
 
 
 
 
 
 
 
 
 
 
Medication History 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Weight 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsi 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Clinical Labsj 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Urinalysisk 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
 
Blood for Serum PD Biomarker Panell 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Fasting morning blood for insulin, 
glucose, cortisolm 
 
 
 
 
 
X 
 
 
 
X 
 
 
Blood for DNA Testing 
 
 
 
 
 
 
 
 
 
 
X 
 
12-lead ECGn 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Dispense Study Medication 
X 
 
 
X 
X 
Xo 
X 
X 
X 
Xo 
X 
 
Return Study Medication/ Compliance 
Monitoring 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Medication Dosing 
 
X 
 
 
 
 
 
 
 
 
X 
 
Vamorolone dose taperingp,q 
 
 
 
 
 
 
 
 
 
 
 
X 
Time to Stand Test (TTSTAND) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Climb Test (TTCLIMB) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Run/Walk Test (TTRW) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
NSAAr 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Quantitative Muscle Testing (QMT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Six-minute Walk Test (6MWT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Pediatric Outcomes Data Collection 
Instrument (PODCI) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Spine x-ray 
 
 
 
 
 
 
 
 
 
 
X 
 
Hand x-ray 
 
 
 
 
 
 
 
 
 
 
X 
 
Dispense Subject Diariess 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Return Subject Diaries  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE Recordingt 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Concomitant Medications 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Discharge from Study 
 
 
 
 
 
 
 
 
 
 
Xu 
Xv 

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d = day(s); w = week.  
a. 
Baseline Day -1, within 24 hours prior to administration of the first dose of study drug.  The Baseline Visit for Study VBP15-LTE can coincide with the Week 24 Final 
Visit for Study VBP15-003, or the final visit following dose-tapering for subjects who dose taper, or may occur up to 8 weeks after the date of the final visit following 
dose tapering. 
b. 
Treatment Day 1 begins at the time of administration of the first dose of VBP15-LTE study medication at home.  No scheduled study visit will occur on Day 1. 
c. 
Subjects who prematurely discontinue from the study prior to Month 24 should complete the Month 24 assessments at the time of early discontinuation. 
d. 
All subjects EXCEPT those who elect to continue vamorolone therapy in a further extension study must continue in the Dose-tapering Period and have their vamorolone 
dose tapered at weekly intervals over a 2-5 week period prior to discharge from this study.  Subjects participating in the Dose-tapering Period will have one study site 
visit during this period, at the end of dose tapering (Months 24-25) (see 6.3.4). 
e. 
Informed Consent for this extension study may be obtained at the Study VBP15-003 Week 24 Final Visit or within 8 weeks after the final dose-tapering visit for subjects 
who dose-taper, after completion of all final VBP15-003 study assessments and prior to any VBP15-LTE extension study-specific procedures.  For all subjects, informed 
consent for VBP15-LTE participation will be given on Study Day -1, within 24 hours of administration of first dose of study medication in VBP15-LTE. 
f. 
Interim Medical History will be collected on Baseline Day -1 for all subjects, and will include any AEs that occurred during the VBP15-003 core study and are ongoing 
at the time of entry into VBP15-LTE (see 7.2.1). 
g. 
Any changes in medication/therapy including administration of new medication(s), change of dose, or discontinuation of medication after completion of the VBP15-003 
core study and prior to administration of the first dose of study medication in VBP15-LTE will be captured as Prior Medications. 
h. 
If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the Week 24 Final Visit in the VBP15-003 core study, these assessments may be used for the VBP15-LTE 
study Baseline assessments.  Clinical laboratory and urinalysis test results from the VBP15-003 Week 24 Final Visit may be used and should be reviewed by the Site 
Investigator to determine eligibility for Baseline Day -1 enrollment into the VBP15-LTE long-term extension study. 
i. 
Supine blood pressure, oral temperature, respiratory rate, and heart rate. 
j. 
Blood for hematology, chemistry, and lipids. 
k. 
Urinalysis by dipstick and microscopic analysis. 
l. 
Blood collected for pharmacodynamic safety biomarkers and exploratory safety and efficacy biomarkers.  
m. Blood will be collected for insulin, glucose, and cortisol determination in the morning after subjects have fasted for ≥ 6 hours, prior to the daily dose of study medication. 
n. 
ECG recorded after subject has rested quietly in a supine position for at least 5 minutes. 
o. 
The dose of study medication on the days of the Month 9 and 21 Visits will be administered after 1) a morning fasting blood draw for insulin, glucose, and cortisol; and 
2) breakfast provided by the study site.  All other doses will be taken at home. 
p. 
Only for subjects who will participate in the Dose-tapering Period. 
q. 
Subjects who elect to switch to standard of care glucocorticoids, or discontinue vamorolone and not begin glucocorticoid treatment for DMD at the end of the study will 
have their vamorolone dose tapered at weekly intervals to a dose of 0 mg/kg/day prior to final study assessments (see 6.3.4). 
r. 
North Star Ambulatory Assessment; includes the Time to Stand Test (TTSTAND). 
s. 
Subject diaries used to record any changes to concomitant medications taken and any AEs experienced during the study. 
t. 
All AEs and SAEs must be collected in the source documents and eCRF from the date of the subject’s written informed consent until the Month 24 Visit or the subject’s 
participation in the study is completed.  Ongoing AEs will be followed to resolution, stabilization, or until such time the Investigator agrees follow-up is not necessary. 
u. 
Subjects who elect to continue vamorolone therapy in a subsequent extension study may be discharged from the study following completion of all final Month 24 
procedures. 
v. 
Subjects who participate in the Dose-tapering Period may be discharged from the study following completion of all final Dose-tapering Visit assessments (see 6.3.4). 
 

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6.2 
Informed Consent/HIPAA Authorization 
The parents or guardians of subjects who choose to enroll in this long-term extension 
study will give written informed consent for this study at the Baseline Day -1 Visit.  If the 
Baseline Day -1 Visit coincides with the VBP15-003 Week 24 Final Visit, the parents or 
guardians of subjects may give written informed consent for this study following 
completion of all VBP15-003 assessments at the final visit.  For subjects who participate 
in the VBP15-003 Dose -tapering Period, informed consent for the VBP15-LTE study 
may be given within 8 weeks after completion of the final VBP15-003 Dose-tapering 
Visit.  The Investigator (or designated staff) will obtain the written informed consent and 
HIPAA authorization, if applicable, from the subject’s parent or guardian prior to any 
extension study-specific procedures.  Each subject’s parent or guardian will receive an 
explanation of the nature and purposes of the study from the Investigator or designee.  
The Investigator or designee will ensure the study is appropriate for the subject.  Reasons 
for exclusion will be documented for subjects found ineligible during the Pretreatment 
Period.  The subject’s parent or guardian will be asked if s/he understands that the study 
is for research purposes only and that it may not provide any therapeutic benefit to the 
subject.  Each subject’s parent or guardian will be asked if s/he understands that the 
subject is free to withdraw from the study at any time without prejudice.  If relevant, the 
Investigator or designee will review the elements of the HIPAA and Protected Health 
Information (PHI) with each subject’s parent or guardian and each subject’s parent or 
guardian will be asked if s/he understands HIPAA authorization and PHI.  Each subject’s 
parent or guardian will be required to sign a study ICF (and HIPAA authorization, if 
applicable) before any procedures are performed for the long-term extension study.  The 
written assent of children will be obtained per individual site guidelines. 
The Investigator or designee will obtain written informed consent from each subject’s 
parent or guardian prior to subject’s participation in the long-term extension study on 
Informed Consent Forms approved by the appropriate IRB/IEC at each site.  Consent 
must be obtained in accordance with the principles outlined in the current version of the 
Declaration of Helsinki.  Informed Consent Forms must be dated and signed by the 
Investigator or designee and the subject’s legal representative and the original signed 

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consent form must be kept by the Investigator in the study subject’s file.  “Legal 
representative” means an individual whom a judicial or other body authorized under 
applicable law to consent on behalf of a prospective study subject to the subject’s 
participation in the procedure(s) involved in the research.  The Study Monitor will ensure 
that the ICF has been signed by the subject’s legal representative.  The study subject’s 
legal representative will receive a copy of the signed consent form. 
6.3 
Visit Schedule and Procedures 
During the study, there will be a total of up to 11 study site visits: Pretreatment Baseline 
Visit (Day -1); Treatment Period Months 1, 3, 6, 9, 12, 15, 18, 21, and 24; and a final 
Dose-tapering Period Visit for subjects whose vamorolone dose is tapered at the end of 
the Treatment Period.  Each subject will receive the investigational product for a period 
of 24 months.  Subjects will initiate dosing in the VBP15-LTE study at the same dose 
level at which they were dosing at the time of the Week 24 Final Visit in the VBP15-003 
Phase IIa core extension study.  The dose level may be increased at the discretion of the 
Study Chair and Medical Monitor once the subject has received the initial dose in the 
VBP15-LTE study for at least one month, the next dosing level has been determined to be 
safe in the VBP15-002 Phase IIa core study, and no safety issues at that dose have 
emerged in the VBP15-003 core study.  Subjects who participate in the Dose-tapering 
Period will receive additional vamorolone at a decreasing dose over 1 to 4 weeks during a 
2- to 5-week Dose-tapering Period, and will return to the study site for final study 
assessments at the end of the Dose-tapering Period.  See Section 7 for a detailed 
description of the safety, clinical efficacy, and PD assessments to be performed in this 
study. 
6.3.1 
Baseline Period (Day -1) 
For all subjects, the Baseline Day -1 Visit will occur after completion of all VBP15-003 
final procedures and within 24 hours prior to administration of the first dose of study 
medication in the VBP15-LTE long term extension study. 
Parents or guardians of subjects who have completed all VBP15-003 study assessments 
will sign the ICF and HIPAA authorization, if applicable, for the VBP15-LTE long term 

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extension study at the Baseline Day -1 Visit.  If either the VBP15-003 Week 24 Final 
Visit or the final visit following dose-tapering for subjects who dose-taper, will coincide 
with Baseline Visit for VBP15-LTE, the VBP15-LTE-specific ICF must be signed after 
completion of all VBP15-003 assessments at the relevant final visit and prior to the 
performance of any VBP15-LTE extension study-specific procedures (Section 6.2). 
Subjects whose VBP15-LTE Baseline Day -1 Visit occurs ≤ 28 days after the 
VBP15-003 Week 24 Final Visit, may use the physical examination, clinical laboratory 
tests, PD biomarker blood draw, 12-lead ECG, and clinical efficacy assessments 
performed at the VBP15-003 Week 24 Final Visit as their Baseline Day -1 Visit 
assessments. 
Subjects will retain the subject identification number assigned for the Phase IIa VBP-002 
and Phase IIa extension VBP15-003 core studies. 
Any new medications taken from the time of completion of the VBP15-003 study to 
administration of the first dose of study medication in the VBP15-LTE study, or any 
changes to medications taken during the VBP15-003 core study, will be recorded as Prior 
Medications on the appropriate eCRF.  See Section 7 for detailed descriptions and 
instructions for completion of each safety, efficacy, and PD assessment. 
The following procedures will be performed at the Baseline Day -1 Visit (see Table 8): 
• 
Review of Inclusion and Exclusion Criteria (see 4.2 and 4.3) 
• 
Written informed consent and HIPAA authorization, if applicable, for the 
VBP15-LTE extension study (see 6.2) 
• 
Enrollment (see 5.9) 
• 
Recording of Interim Medical History (see 7.2.1) 
• 
Recording of Medication History (see 5.7.1) 
• 
Recording of AEs and SAEs beginning at the time written informed consent is 
obtained (see 7.2.6) 
• 
Complete physical examination (not to be repeated if Baseline Day -1 is ≤ 28 days 
after the VBP15-003 Week 24 Final Visit assessment date) (see 7.2.2). 
• 
Measurement of height and weight (see 7.2.2) 

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• 
Recording of vital signs (supine blood pressure, heart rate, oral temperature, 
respiratory rate) (see 7.2.3) 
• 
Clinical laboratory evaluation including hematology, clinical chemistry, lipids, 
and urinalysis tests (not to be repeated if Baseline Day -1 is ≤ 28 days after the 
VBP15-003 Week 24 Final Visit assessment date) (see 7.2.4) 
• 
Blood samples for PD biomarkers.  Blood will also be collected and stored for 
exploratory PD biomarkers.  (Not to be repeated if Baseline Day -1 is ≤ 28 days 
after the VBP15-003 Week 24 Final Visit assessment date.)  (see 7.3.7) 
• 
12-lead ECG (not to be repeated if Baseline Day -1 is ≤ 28 days after the 
VBP15-003 Week 24 Final Visit assessment date) (see 7.2.5) 
• 
Time to Run/Walk Test (TTRW) (not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 7.3.3) 
• 
Time to Stand Test (TTSTAND) (not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 7.3) 
• 
Time to Climb Test (TTCLIMB) (not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 7.3.2) 
• 
North Star Ambulatory Assessment (NSAA) (not to be repeated if Baseline Day -
1 is ≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 
7.3.4) 
• 
Six-minute Walk Test (6MWT) (not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 7.3.5) 
• 
Quantitative Muscle Testing (QMT) (not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date) (see 7.3.6) 
• 
Pediatric Outcomes Data Collection Instrument (PODCI) completed by 
parent/legal guardian (see 7.3.8). 
• 
Dispensing of study medication and subject diaries (see 5.3 and  
8.4) 
6.3.2 
Treatment Period Day 1 
Treatment Period Day 1 begins with administration of the first dose of study medication.  
There is no scheduled clinic visit on Day 1. 

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Subjects will take the first dose of study medication at home on the morning of the day 
after the Day -1 Visit, on Study Day 1 with a full glass of whole milk (approximately 8 
grams of fat) or a serving of an equivalent fat amount of a high fat food, under the 
supervision of a parent or guardian (5.3). 
6.3.3 
Treatment Period Months 1-24 
Subjects will return to the study site for safety, efficacy, and PD assessments beginning at 
Month 1 and continuing through Month 24, according to the schedule of visits in Table 8. 
Subjects will continue to receive daily oral administration of vamorolone throughout the 
24-month Treatment Period, taken following ingestion of a full glass of whole milk 
(approximately 8 grams of fat) or a serving of an equivalent fat amount of high fat food. 
Dosing is to occur at home throughout the 24-month Treatment Period, except at the 
Month 9 and Month 21 Visits when dosing will occur at the study site to accommodate 
morning fasted blood collections.  Subjects must have fasted ≥ 6 hours prior to arrival at 
the study site for Month 9 and Month 21 procedures and assessments.  The pre-dose 
blood draws for PD (insulin, glucose, and cortisol only) determination must be collected 
after subjects have fasted for ≥ 6 hours.  Breakfast (a glass of whole milk [approximately 
8 grams of fat] or an equivalent high fat food portion and 1 cup of cereal) will be served 
at the study site after the blood draw for insulin, glucose, and cortisol, and within 
approximately 30 minutes prior to administration of the dose of study medication.  All 
other Month 9 and Month 21 assessments should be performed after administration of the 
dose of study medication. 
Clinical efficacy assessments (TTSTAND, TTRW, TTCLIMB, NSAA, 6MWT, and 
QMT) and the Pediatric Outcomes Data Collection Instrument (PODCI) will be 
conducted at 12 and 24 months.  Weight will be recorded every visit from 3-24 months 
and height will be measured at 12 and 24 months.  Vital signs will be recorded at each 
study visit.  A physical examination will be performed at Months 12 and 24.  A 12-lead 
ECG will be recorded at Months 12 and 24.  Blood and urine samples for clinical 
laboratory tests, and blood for PD biomarkers will be collected at 6, 12, 18, and 24 
months (see Table 8).  Blood will be collected at Month 24 for DNA testing for 

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established genetic modifiers of DMD.  Spine x-ray and hand x-ray will be performed at 
Month 24.  Adverse events, including SAEs, and concomitant medications will be 
assessed at each study visit and recorded throughout the study. 
Study medication will be dispensed and returned at 3-month intervals for all subjects.  
Subjects will receive subject diaries at Baseline Day -1 visit and each scheduled 3-month 
visit and return the diaries at each subsequent visit; diaries returned at the Month 1 Visit 
will be reviewed by study staff for accuracy and returned to the subjects for continued 
use through the time of the Month 3 Visit.  Diaries will be reviewed with the subject’s 
parent or guardian by the study staff to assess AEs and changes to concomitant 
medications/therapies. 
Subjects who will not participate in the Dose-tapering Period (see Section 6.3.4) will be 
discharged from the study following completion of all Month 24 assessments.  Subjects 
who do participate in the Dose-tapering Period will be dispensed vamorolone (and 
standard of care glucocorticoid at the discretion of the Investigator for subjects who elect 
to transition to standard of care glucocorticoid treatment) at the Month 24 Visit, as well 
as instructions for tapering the dose of vamorolone during the Dose-tapering Period. 
6.3.4 
Dose Tapering Period (Months 24-25) 
Subjects who elect to transition to standard of care glucocorticoid treatment for DMD, or 
discontinue vamorolone and not begin standard of care glucocorticoid treatment for 
DMD at the end of the study will have their vamorolone dose tapered prior to discharge 
from the study.  Subjects who discontinue study medication prior to completion of 
Month 24 assessments will also participate in the Dose-tapering Period if possible and if, 
in the opinion of the Investigator, it is safe to do so.  Dose tapering will be performed in a 
stepwise manner, according to the subject’s vamorolone dose at completion of the 
24-month Treatment Period, as outlined in Table 9.  Subjects who elect to transition to a 
standard of care glucocorticoid will have their vamorolone dose tapered as in Table 9, 
and will begin treatment with a standard of care glucocorticoid on the day dose tapering 
begins.  These subjects will continue to receive standard of care glucocorticoid treatment, 

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with drug and dose at the discretion of the Investigator, throughout the duration of the 
Dose-tapering Period and after discharge from the study. 
The subject’s weight recorded at the Month 24 Visit will be used to calculate dose and 
dose volume for all dose de-escalations during the Dose-tapering Period (see 
Appendix 14.1). 
Table 9 
Vamorolone Dose Tapering 
Treatment Period 
Vamorolone Dose 
Level at Month 24 
Final Visit 
Dose Level for 
First Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Second Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Third Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fourth Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fifth Week 
Following the 
Month 24 
Final Visit 
0.25 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
 
0.75 mg/kg/day 
0.375 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
2.0 mg/kg/day 
1 mg/kg/day 
0.5 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
 
4.0 mg/kg/day 
2 mg/kg/day 
1 mg/kg/day 
0.5 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
6.0 mg/kg/day 
3 mg/kg/day 
1.5 mg/kg/day 
0.75 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
 
All subjects participating in the Dose-tapering Period will return to the study site for final 
study assessments approximately one week after the final dose de-escalation (i.e., 
approximately one week after the subject has received his last dose of vamorolone).  The 
duration of the Dose-tapering Period will therefore vary depending upon the vamorolone 
dose received by the subject at completion of the Month 24 Visit of the Treatment Period, 
from a total duration of two weeks (for subjects receiving 0.25 mg/kg/day vamorolone; 
final study visit two weeks following the Month 24 Final Visit) to five weeks (for 
subjects receiving vamorolone 4.0 mg/kg/day or 6.0 mg/kg/day; final study visit five 
weeks following the Month 24 Final Visit). 
At the final study visit following the Dose-tapering Period, subjects participating in the 
Dose-tapering Period will have vital signs recorded, and blood collected for clinical 
laboratory tests and PD biomarker panel.  Study medication will be returned for 
compliance monitoring.  Adverse events, including SAEs, and concomitant medications 
will be assessed.  Subject diaries will be returned and reviewed with site staff. 

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Subjects participating in the Dose-tapering Period will be discharged from the study 
following completion of all final Dose-tapering Period assessments. 
6.4 
Subject Discontinuation 
In the event that a subject withdraws early from the study prior to the Month 24 Final 
Visit, the reason for discontinuation must be fully documented in the source documents 
and the eCRF.  For subjects who withdraw early, final Month 24 assessments should be 
performed at the time of early discontinuation (see Section 6.3.3).  Site personnel will 
document all assessments, including any AEs, in the source documents and eCRF.  
Subjects who discontinue study medication should follow vamorolone dose tapering 
procedures described in Section 6.3.4 and detailed in the Manual of Operations. 
6.5 
Study Completion 
A completed subject is defined as a subject who has completed the 24-month Treatment 
Period and Dose-tapering Period, if applicable, and has not prematurely withdrawn from 
the study for any reason. 
7 
STUDY ASSESSMENTS AND MEASUREMENTS 
7.1 
Demographic Assessments 
Demographic information (birth date, race, and ethnicity) collected during the 
VBP15-002 study will be used for this study; collection of demographic data will not be 
repeated during this study. 
7.1.1 
Genetic Modifiers of DMD 
Approximately 8.5 mL of blood will be collected at the Month 24 Visit for DNA testing 
to determine if established genetic modifiers of DMD (gene polymorphisms associated 
with disease severity or response to glucocorticoid treatment) are similarly associated 
with vamorolone-treated DMD patients (baseline disease severity or response to 
vamorolone treatment).   
DNA testing will be performed by a certified central laboratory. 

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The procedures for the collection, handling, and shipping of blood samples for DNA 
testing will be specified in the Laboratory Manual(s) provided to the clinical center.  
Results will be compared to historical control data for glucocorticoid responders and 
non-responders. 
7.2 
Safety and Tolerability Assessments 
7.2.1 
Interim Medical History 
At the Baseline Day -1 Visit, interim medical history will be recorded for each subject, 
including medical history migrated from the VBP15-003 core study and any medical 
history that occurred in the period between completion of VBP15-003 and enrollment 
into the VBP15-LTE long term extension study.  Migrated medical history will include 
any condition that was recorded as medical history for the VBP15-003 Phase IIa 
extension core study.  Medical history occurring between completion of VBP15-003 and 
VBP15-LTE enrollment will include surgical history and concurrent diseases, including 
any changes from the core study.  All AEs that are recorded during the VBP15-003 core 
study and are ongoing at the time of enrollment into the VBP15-LTE study will be 
recorded as medical history in the VBP15-LTE study. 
Interim medical history will be recorded in the source documents and in the eCRF. 
7.2.2 
Physical Examination, Weight, and Height 
A complete physical examination will be performed at the Baseline Day -1, Month 12, 
and Month 24 Visits, and will include examination of the following: head, eyes, ears, 
nose, and throat, neck (including an examination of the thyroid), heart, lungs, abdomen 
(including an examination of the liver and spleen), lymph nodes, extremities, nervous 
system, and skin.  If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the 
VBP15-003 Phase IIa extension core study Week 24 Final Visit, the Baseline Day -1 
physical examination does not need to be repeated (results from the VBP15-003 Week 24 
Final Visit may be used as the Baseline assessment). 
Additional unscheduled symptom-directed physical examinations may be conducted at 
any time at the Investigator’s discretion. 

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Height (in cm) will be recorded at Baseline Day -1, and Months 12 and 24.  Weight 
(in kg) will be recorded at Baseline Day -1, Months 3, 6, 9, 12, 15, 18, 21, and 24.  
Weight recorded at each scheduled visit will be used to calculate the vamorolone dose 
volume for each subsequent period’s dosing (see Appendix 14.1). 
Results will be recorded in the source documents and on the appropriate eCRF. 
7.2.3 
Vital Signs 
Vital signs (supine blood pressure, heart rate, respiration rate, and oral temperature) will 
be recorded at Baseline Day -1, and each scheduled visit thereafter through Month 24, 
and at the final study visit following dose-tapering for subjects who dose-taper.  Vital 
signs should be recorded after the subject has been resting for at least 5 minutes. 
Results will be recorded in the source documents and on the appropriate eCRF. 
If vital signs assessment is performed at the same study visit as blood sampling and ECG 
recording, the following sequence should be followed:  1) ECG recording; 2) vital signs 
assessment; and 3) blood sampling. 
7.2.4 
Clinical Laboratory Tests 
Each subject will have blood drawn and urine collected for the hematology, chemistry, 
lipids, and urinalysis clinical laboratory tests listed in Table 10 and Table 11, below, at 
the Baseline Day -1, and Month 6, 12, 18, and 24 Visits.  Subjects whose dose is tapered 
will also have clinical laboratory tests performed at the final visit following  the Dose-
tapering Period.  If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the 
VBP15-003 Phase IIa extension core study Week 24 Final Visit, clinical laboratory test 
results from that visit may be used as baseline measurements for the VBP15-LTE study. 
For all subjects, the clinical laboratory test results obtained at the VBP15-003 Week 24 
Final Visit will be used to assess extension study eligibility. 
All blood and urine samples will be sent to the designated central laboratory for testing. 
For the hematology, chemistry, and lipids laboratory tests, blood will be collected by 
direct venipuncture of peripheral veins.  Approximately 4.5 mL of blood will be obtained 
for clinical laboratory tests at each scheduled visit.  A total of approximately 18-27 mL of 

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blood will be collected over the course of this study for clinical laboratory evaluation (see 
Section 7.4 for details of blood volumes to be collected). 
If blood sampling is performed at the same study visit as vital signs assessment and ECG 
recording, the following sequence should be followed:  1) ECG recording; 2) vital signs 
assessment; and 3) blood sampling. 
Any abnormal hematology, chemistry, lipid, or urinalysis test result deemed clinically 
significant by the Investigator or medically qualified sub-investigator may be repeated, 
including test results obtained on the final study day. 
Any treatment-emergent abnormal laboratory test result that is clinically significant, i.e., 
meeting one or more of the following conditions, should be recorded as a single diagnosis 
on the AE section of the eCRF: 
• Accompanied by clinical symptoms 
• Requiring a change in concomitant therapy (e.g., addition of, interruption of, 
discontinuation of, or any other change in a concomitant medication, therapy, or 
treatment) 
• Is otherwise considered clinically significant by the Investigator 
Any clinically significant test abnormality as defined above should be recorded as an AE 
(unless it was considered spurious), and repeat analysis performed until resolution or 
until the Investigator or medically qualified sub-investigator determines that resolution of 
the abnormality is not expected. 

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Table 10 
Hematology, Chemistry, and Lipids Clinical Laboratory Tests 
Hematology 
Red Blood Cells (RBC) 
Numerical platelet count (estimate not acceptable) 
Hemoglobin 
White Blood Cells (WBC) with differential (percent) 
Hematocrit 
 
 
 
Chemistry 
Sodium 
Total Bilirubina 
Potassium 
Uric Acid 
Chloride 
Glucose 
Calcium 
Alkaline phosphatase (ALP) 
Inorganic Phosphorus 
Gamma Glutamyl Transferase (GGT) 
Blood Urea Nitrogen (BUN) 
Aspartate aminotransferase (AST) 
Creatinine 
Alanine aminotransferase (ALT) 
Total Protein 
Creatine kinase (CK) 
Albumin 
Lipase  
Bicarbonate 
Amylase  
Lactate Dehydrogenase (LDH) 
 
 
 
Lipids 
Triglycerides 
Low Density Lipoprotein (LDL) 
Total cholesterol 
High density Lipoprotein (HDL) 
a. If outside normal range, direct bilirubin will be measured and reported. 
Urine will be collected for routine analysis, by dipstick and microscopic analysis, for the 
tests described in Table 11.  Urine will be analyzed by dipstick and microscopic analysis 
by the central laboratory at all assessment time points. 
Table 11 
Urinalysis Clinical Laboratory Tests 
Urinalysis (including microscopic examination) 
Dipsticka 
Microscopic Analysis 
Protein 
WBC/hpf 
Glucose 
RBC/hpf  
Ketones 
Casts 
pH 
Bacteria 
Leukocyte esterase 
 
Blood 
 
aA midstream clean-catch urine specimen will be collected 
for dipstick analysis.   

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Clinical laboratory tests will be performed by a central laboratory; results will be reported 
to the study site and transferred electronically into the clinical study database. 
The procedures for the collection, handling, and shipping of laboratory samples will be 
specified in the Laboratory Manual(s) provided to the clinical center. 
7.2.4.1 
Follow-up of Abnormal Laboratory Test Results 
In the event of a medically significant, unexplained, or abnormal clinical laboratory test 
value, the test(s) may be repeated, evaluated by the Investigator for sustainability and 
reproducibility to determine if the abnormality represents an AE, and followed-up until 
the results have returned to the normal range, stabilized, and/or an adequate explanation 
for the abnormality is found.  If a clear explanation is established, it should be recorded in 
the source documents and eCRF.  The clinical laboratory will clearly mark all laboratory 
test values that are outside the normal range and the Investigator will indicate which of 
these deviations are clinically significant.  These clinically significant deviating 
laboratory results will then be further described as AEs, and the relationship to the 
treatment, in the Investigator’s opinion, will be indicated (see Section 7.2.6). 
7.2.5 
12-Lead ECG 
12-lead ECGs will be collected at the Baseline Day -1, Month 12 and Month 24 Visits.  If 
the Baseline Day -1 Visit occurs ≤ 28 days after the date of the VBP15-003 Phase IIa 
extension core study Week 24 Final Visit, the Baseline Day -1 12-lead ECG does not 
need to be repeated (results from the VBP15-003 Week 24 Final Visit may be used).  All 
ECG recordings must be performed using a standard high-quality, high-fidelity machine 
equipped with computer-based interval measurements.  Digital ECG recording is 
recommended.  Automated ECG intervals (QRS duration, PR [PQ] interval, RR interval 
[interbeat interval], QT interval, QTc, and heart rate) will be captured or calculated. 
12-lead ECGs will be obtained over a 3- to 5-minute period after the subject has been 
resting quietly in a supine position for at least 5 minutes. 

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If blood sampling, vital signs assessment, and ECG recordings are scheduled at the same 
study visits, the following sequence should be followed:  1) ECG recording; 2) vital signs 
assessment; and 3) blood sampling. 
ECG results will be read locally.  Results must be interpreted and recorded on the 
appropriate eCRF. 
7.2.6 
Adverse Events and Serious Adverse Events 
The condition of the subjects will be monitored throughout the duration of the study by 
the clinical site study team and by recording of AEs in subject diaries.  An AE is any 
untoward medical occurrence in a subject which does not necessarily have to have a 
causal relationship with the intervention.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or 
disease temporally associated with the use of an investigational product, whether or not 
considered related to the product.  Pre-existing conditions that worsen during a study are 
to be reported as AEs. 
Adverse events will be recorded from the date of informed consent and through the time 
of the subject’s last study visit (study completion or early discontinuation).  Serious 
adverse events will be recorded from the date of informed consent, throughout the 
clinical trial, and for up to 30 days after the final administration of study drug.  Subjects 
who enroll in the VBP15-LTE long term extension study will have any AEs which 
initiated during VBP15-003 participation and which are ongoing at the time of enrollment 
into VBP15-LTE recorded as Medical History in the VBP15-LTE eCRF.  In addition, 
subjects (and their parent or legal guardian) will be questioned by study staff at each 
study visit for any new signs or symptoms or changes in existing signs or symptoms. 
All AEs and SAEs that are spontaneously reported, identified during questioning, or are 
apparent from a participant’s physical appearance will be recorded in the source 
documents and in the subject’s eCRF.  The date of onset will be recorded.  Any 
laboratory abnormality that is outside the normal range and is considered an AE (see 
Section 7.2.4) should be recorded as an AE on the appropriate eCRF.  The details 
recorded shall include the nature, date of onset, final outcome and its date, intensity 

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assessment (Common Terminology Criteria for Adverse Events [CTCAE] grade), and a 
determination of the relationship of the event to administration of the study drug (i.e., 
causality).  All AEs will be graded by CTCAE, Version 4.03.  Details of any medications 
given to the subject to abate the AE should be recorded in the appropriate eCRF. 
Intensity 
All clinical AEs encountered during the clinical study will be recorded in the eCRF.  
Intensity of AEs will be graded using the most current version of the Common 
Terminology Criteria for Adverse Events (CTCAE), version 4.03, 5-point scale, and 
reported in detail as indicated on the eCRF.  A description of the intensity scales can be 
found below: 
Mild (Grade 1):  Asymptomatic or mild symptoms: clinical or diagnostic observations 
only; intervention not indicated. 
Moderate (Grade 2):  Minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL). 
Severe (Grade 3):  Severe or medically significant but not immediately life-
threatening: hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL; incapacitating with inability to work or perform normal daily 
activity. 
Life-Threatening (Grade 4):  Urgent intervention indicated. 
Death (Grade 5):  Death related to AE. 
Relationship 
Relationship to study drug will be graded on a 5-point scale (definite, probable, possible, 
remote, or unrelated).  A description of the relationship scale can be found below: 
Definite:  This category applies to an AE that meets at least criteria 1, 2, and 4 of the 
“Probable‟ category. 
Probable:  This category applies to those AEs that are considered, with a high degree 
of certainty, to be related to the study drug.  An AE may be considered probable, if 
(must include first 3): 

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1. It follows a reasonable temporal sequence from administration of the study 
drug. 
2. It cannot be reasonably explained by the known characteristics of the subject’s 
clinical state, environmental or toxic factors, or other modes of therapy 
administered to the subject. 
3. It disappears or decreases after dosing is complete.  (There are important 
exceptions when an AE does not disappear upon discontinuation of study 
drug, yet drug relatedness clearly exists, e.g., [1] bone marrow depression and 
[2] tardive dyskinesia.)  
4. It follows a known pattern of response to the suspected study drug. 
Possible:  This category applies to those AEs for which the connection with study 
drug administration appears unlikely but cannot be ruled out with certainty.  An AE 
may be considered possibly related to study drug if or when (must include first 2): 
1. It follows a reasonable temporal sequence from administration of the study 
drug. 
2. It may have been produced by the subject’s clinical state, environmental or 
toxic factors, or other modes of therapy administered to the subject. 
3. It follows a known pattern of response to the suspected study drug. 
Remote:  In general, this category is applicable to an AE that meets the following 
criteria (must include the first 2): 
1. It does not follow a reasonable temporal sequence from administration of the 
study drug. 
2. It may readily have been produced by the subject’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the 
subject. 
3. It does not follow a known pattern of response to the suspected study drug. 
Unrelated: This category is applicable to those AEs which are judged to be clearly 
and incontrovertibly due only to extraneous causes (disease, environment, etc.) and 

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do not meet the criteria for study drug relationship listed under remote, possible, or 
probable. 
Clinical Laboratory Test Abnormalities 
Clinical laboratory test results will be recorded in the designated eCRF.  The intensity of 
abnormal clinical laboratory test results that are AEs will also be graded using the most 
current version of the CTCAE, version 4.03, 5-point scale and reported in detail as 
indicated in the eCRF.  A description of the intensity scale can be found above. 
Any treatment-emergent abnormal clinical laboratory test result that is clinically 
significant, i.e., meeting one or more of the following conditions, should be recorded as a 
single diagnosis on the AE section of the eCRF: 
• Accompanied by clinical symptoms 
• Requiring a change in concomitant therapy (e.g., addition of, interruption of, 
discontinuation of, or any other change in a concomitant medication, therapy, or 
treatment) 
• Is otherwise considered clinically significant by the Investigator 
This applies to any protocol and non-protocol-specified safety laboratory result from tests 
performed after the first dose of study drug, which falls outside the laboratory reference 
range and meets the clinical significance criteria per Investigator standard operating 
procedures (SOPs). 
This does not apply to any abnormal laboratory result that falls outside the laboratory 
reference range, but does not meet the clinical significance criteria (which will be 
analyzed and reported as laboratory abnormalities); those that are considered AEs of the 
type explicitly exempted by the protocol; or those that are the result of an AE which has 
already been reported. 
Please Note: any clinical laboratory abnormality fulfilling the criteria for an SAE should 
be reported as such, in addition to being recorded as an AE in the eCRF. 

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Follow-Up of Adverse Events 
Adverse events will be followed until they have returned to baseline status, stabilized, or 
the Investigator, Study Chair, Medical Monitor and Sponsor agree that follow-up is no 
longer needed.  If a clear explanation of cause is established, it should be recorded in the 
source documents and eCRF.  In the event of unexplained abnormal laboratory test 
values, the tests may be repeated as soon as possible and followed up until they have 
returned to the normal range or baseline value and/or an adequate explanation of the 
abnormality is found.  In case of ongoing AEs at the time of database closure, the data 
obtained at the time of database closure will be used in the statistical analysis.  The 
follow-up of AEs will be documented in the source documents and will be described in 
the final report only if considered relevant by the Investigator, the Study Chair, the 
Medical Monitor and/or the Sponsor. 
In addition, the Medical Monitor may request additional blood tests, diagnostic imaging 
studies, or specialist physician consultations in order to further evaluate any AE or test 
abnormality considered to be clinically significant by the Study Sponsor. 
Dosing Error 
For the purposes of this study, a dosing error is defined as a dose exceeding or less than 
the scheduled dose of 0.25 mg/kg, 0.75 mg/kg, 2.0 mg/kg, or 6.0 mg/kg specified for 
each dose level group.  Such occurrences should be reported and recorded in the dosing 
page of the eCRF and as follows: 
• Use of study medication in doses in excess of that specified in the protocol should 
not be recorded as an AE unless there are associated signs or symptoms. 
• A dosing error with associated non-serious AEs should be recorded as AEs on the 
relevant AE forms in the eCRF. 
• A dosing error with an associated SAE should be recorded as an SAE. 
• Details of all dosing errors, including actual dose administered, should be 
documented in the source documents. 

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7.2.6.1 
Serious Adverse Events 
For treatment-eligible subjects, SAEs will be collected and reported during the study 
from the time informed consent is obtained through 30 days after the final dose of study 
medication, according to the protocol and applicable regulations. 
All SAEs, including those that continue beyond the normal AE collection period (i.e., are 
ongoing at the subject’s last study visit), will be followed until resolution or until 
stabilized without sequelae.  Serious adverse events that begin after the subject’s 
participation in the study is complete but that the Investigator considers to be related to 
study drug will be reported to the Sponsor within 24 hours or discovery by the 
Investigator. 
During the SAE collection period, the Investigator or clinical site personnel should notify 
the PRA safety management team of all SAEs, regardless of relationship to the 
investigational drug, within 24 hours of clinical staff becoming aware of the event; 
notification to the PRA safety management team will trigger alerts to the Coordinating 
Center, Study Chair, the Sponsor, and the Medical Monitor.  The Investigator will 
provide the initial notification by completing the SAE eCRF in the electronic data capture 
(EDC), which must include the Investigator’s assessment of the relationship of the event 
to investigational drug. In the unlikely event that the electronic study database is 
inaccessible and the Investigator is unable to complete the SAE eCRF within 24 hours, 
the SAE Notification Form (pdf) should be completed and emailed or printed/faxed to the 
PRA safety management team. 
In addition, notification is sent by the Investigator to the IRB and the subject’s Primary 
Care Physician. 
Follow-up information, or new information regarding an ongoing SAE, must be provided 
promptly to the PRA safety management team within 24 hours of knowledge of the new 
or follow-up information, which will forward the information to the Coordinating Center, 
Study Chair, the Sponsor, and the Medical Monitor. 
The Data and Safety Monitoring Board (DSMB) will review SAEs at regular intervals 
during the study. 

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All SAE reports should be completed within the EDC. 
An AE or suspected adverse reaction is considered serious if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Is fatal (results in the outcome of death) 
• Is life-threatening  
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions 
• Is a congenital anomaly or birth defect 
• Is an important medical event that may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
The term “sudden death” should only be used when the cause is of a cardiac origin as per 
standard definition. 
The terms death and sudden death are clearly distinct and must not be used 
interchangeably. 
Any AE or clinically significant abnormal laboratory test value, as determined by the 
Investigator, that is serious and which occurs during the course of the study (as defined 
above) must be reported to the PRA safety management team, who will notify the 
Coordinating Center, Study Chair, the Sponsor, and the Medical Monitor within 24 hours 
of the Investigator becoming aware of the event.  Additional information that becomes 
available for an SAE after the initial report is submitted will be reported to the PRA 
safety management team, who will notify the Coordinating Center, Study Chair, the 
Sponsor, and the Medical Monitor within 24 hours of the Investigator becoming aware of 
the new information. 
Related SAEs MUST be collected and reported regardless of the time elapsed from the 
last administration of study drug, even if the study has been closed.  Unrelated SAEs 
must be collected and reported during the study from the time of informed consent 
through 30 days after the final dose of study medication. 

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If, at any time during the study, a subject experiences an SAE, appropriate care should be 
instituted. 
In the event of an SAE, the Investigator will complete the SAE eCRF within 24 hours of 
first awareness of the event. In the unlikely event that the electronic study database is 
inaccessible and the Investigator is unable to complete the SAE eCRF within 24 hours, 
the SAE Notification Form (pdf) should be completed and emailed or printed/faxed to the 
PRA safety management team within 24 hours, using the contact information below: 
Email CHOSafety@prahs.com 
Drug Safety Fax: 1-888-772-6919 or 1-434-951-3482 
 
SAE Questions: Drug Safety Hotline: 1-800-772-2215 or 1-434-951-3489 
Serious Adverse Events will be recorded from the time the subject’s written informed 
consent is obtained.  Serious adverse events that occur within 30 days of study drug 
dosing must continue to be recorded and reported to the Study Sponsor or its designee.  
Should there be an SAE that occurs that suggests an increased risk to the participants, the 
following steps will be considered, depending on the number and severity of the SAE(s): 
modification of the protocol, investigation of the relationship of the SAE(s) to study drug, 
suspension of the study, and/or discontinuation of the study. 
7.2.7 
Bone Age (Hand X-ray) 
Bone age will be assessed by hand x-ray at the Month 24 Visit.  Hand radiography will be 
performed as described in the Manual of Operations.  Hand radiographs will be analyzed 
centrally by a certified radiologist through the imaging coordinating center in Ottawa, 
Canada.   
7.2.8 
Spine X-ray 
Data on bone health will also be collected by lateral spine x-ray (T4-L5) at the Month 24 
Visit.  Lateral spine x-rays will be analyzed centrally by two certified pediatric 
radiologists at Children’s Hospital of Ottawa in Ottawa, Canada, who are blinded to the 
results of one another; a third radiologist will resolve any discrepancies arising from the 
first two readings.  Quantification of any vertebral fractures detected will be performed.   

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Fractures will be recorded as AEs. 
7.3 
Clinical Efficacy and Pharmacodynamic Assessments 
7.3.1 
Time to Stand Test (TTSTAND) 
The Time to Stand Test (TTSTAND) will be administered to subjects at the Baseline 
Day -1, Month 12 and Month 24 Visits.  If the Baseline Day -1 Visit occurs ≤ 28 days 
after the date of the VBP15-003 Phase IIa extension core study Week 24 Final Visit, the 
Baseline Day -1 TTSTAND does not need to be repeated (results from the VBP15-003 
Week 24 Final Visit may be used). 
The TTSTAND measures the speed (rise/second; velocity) with which the child can stand 
to an erect position from supine (floor), and is administered as part of the NSAA (see 
Section 7.3.4).  Complete instructions for administering and scoring the TTSTAND are 
given in the study manual to be supplied to the sites prior to study start. 
Results will be recorded in the source documents and in the eCRF. 
7.3.2 
Time to Climb Test (TTCLIMB) 
The Time to Climb Test (TTCLIMB) will be administered to subjects at the Baseline 
Day -1, Month 12 and Month 24 Visits.  If the Baseline Day -1 Visit occurs ≤ 28 days 
after the date of the VBP15-003 Phase IIa extension core study Week 24 Final Visit, the 
Baseline Day -1 TTCLIMB does not need to be repeated (results from the VBP15-003 
Week 24 Final Visit may be used). 
The TTCLIMB measures the time (in seconds) required for the subject to climb 
4 standard stairs, beginning and ending in a standing position with arms at the sides.50  
Complete instructions for administering the TTCLIMB are given in the study manual to 
be supplied to the sites prior to study start. 
Results will be recorded in the source documents and in the eCRF. 
7.3.3 
Time to Run/Walk Test (TTRW) 
The TTRW will be administered to subjects at the Baseline Day -1, Month 12 and 
Month 24 Visits.  If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the 

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VBP15-003 Phase IIa extension core study Week 24 Final Visit, the Baseline Day -1 
TTRW does not need to be repeated (results from the VBP15-003 Week 24 Final Visit 
may be used). 
The Time to Run/Walk Test (TTRW) measures the time (in seconds) that it takes a 
subject to run or walk 10 meters and is administered as part of the NSAA (see Section 
7.3.4).  Complete instructions for administering and scoring the TTRW are given in the 
study manual to be supplied to sites prior to study start. 
Results will be recorded in the source documents and in the eCRF. 
7.3.4 
North Star Ambulatory Assessment (NSAA) 
The North Star Ambulatory Assessment (NSAA) is a clinical assessment scale 
specifically designed to measure functional ability in ambulant boys with DMD.51  The 
NSAA consists of 17 scored items and 2 timed tests, including the TTRW and the 
TTSTAND (see Section 7.3).  The NSAA will be conducted at the Baseline Day -1, 
Month 12 and Month 24 Visits.  If the Baseline Day -1 Visit occurs ≤ 28 days after the 
date of the VBP15-003 core study Week 24 Final Visit, the Baseline Day -1 NSAA does 
not need to be repeated (results from the VBP15-003 Week 24 Final Visit may be used). 
Subjects should be barefoot and wear comfortable clothing. Complete instructions for 
administering and scoring the NSAA are given in the study manual to be supplied to the 
sites prior to study start. 
The NSAA should be administered BEFORE the 6MWT at study visits where both tests 
are administered. 
Results will be recorded in the source documents and in the eCRF. 
7.3.5 
Six-minute Walk Test (6MWT) 
Functional exercise capacity and mobility will be assessed in all subjects by means of the 
Six-minute Walk Test (6MWT) at the Baseline Day -1, Month 12 and Month 24 Visits.  
If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the VBP15-003 Phase IIa 
extension core study Week 24 Final Visit t, the Baseline Day -1 6MWT does not need to 
be repeated (results from the VBP15-003 Week 24 Final Visit may be used). 

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This evaluation is a modified version of the 6MWT, adapted for use in DMD patients.52 
The total distance traveled, in meters, should be recorded along with the validity of the 
test as assessed by the test administrator in the source documents and in the eCRF.  If a 
subject cannot complete 6 minutes of walking, the total meters and the time until 
discontinuation of the test should be recorded.  Complete instructions for administering 
the 6MWT are given in the study manual to be supplied to the sites prior to study start. 
The 6MWT should be administered AFTER the NSAA at study visits where both tests 
are administered. 
Results will be recorded in the source documents and in the eCRF. 
7.3.6 
Quantitative Muscle Testing (QMT) 
Quantitative Muscle Testing (QMT) will be administered to subjects at the Baseline 
Day -1, Month 12, and Month 24 Visits using the CINRG Quantitative Measurement 
System (CQMS).53  If the Baseline Day -1 Visit occurs ≤ 28 days after the date of the 
VBP15-003 Phase IIa extension core study Week 24 Final Visit, the Baseline Day -1 
QMT does not need to be repeated (results from the VBP15-003 Week 24 Final Visit 
may be used). 
The QMT measures unilateral strength of four muscle groups: elbow flexion/extension, 
and knee flexion/extension.53  Complete instructions for administering the QMT are 
given in the study manual to be supplied to the sites prior to study start. 
Results will be collected using the CQMS3 software and transferred into the eCRF. 
7.3.7 
Pharmacodynamic Biomarker Panel 
Blood samples will be collected to explore the effect of vamorolone on biomarkers of 
muscle cellular pathology, biomarkers associated with chronic glucocorticoid treatment, 
and biomarkers associated with insulin resistance, adrenal suppression, and bone 
turnover, as listed in Table 12.  Blood samples will be collected at the Baseline Day -1 
and Month 6, 12, 18, and 24 Visits, and at the final Dose-tapering Period Visit for 
subjects whose vamorolone dose is tapered at the end of the study.  If the Baseline Day -1 
Visit occurs ≤ 28 days after the date of the VBP15-003 Phase IIa extension core study 

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Week 24 Final Visit, the Baseline Day -1 pharmacodynamic biomarker blood draw does 
not need to be repeated (results from the VBP15-003 Week 24 Final Visit may be used).  
Blood samples for PD biomarkers will be drawn after completion of functional tests at 
the Baseline, and Months 12 and 24 Visits. 
Blood will also be collected at each of these time points and stored for exploratory 
efficacy and safety pharmacodynamic biomarkers. 
Morning, fasted blood samples will be collected at the Month 9 and 21 Visits for 
measurement of fasting glucose, insulin, and cortisol after the subject has fasted for ≥ 6 
hours and prior to administration of the daily dose of study medication. 
A total of 78-110 mL of blood will be collected for PD biomarkers over the course of the 
24-month study (see Section 7.4). 
Table 12 
Pharmacodynamic Biomarkers 
Adrenal Suppression 
Morning Cortisol 
ACTH 
17- hydroxyprogesterone 
Testosterone 
Corticosterone 
11- deoxycortisol 
Insulin Resistance 
Fasting Glucose 
Fasting Insulin 
HbA1c 
Bone Turnover 
Osteocalcin 
CTX1 
P1NP 
Exploratory Biomarkers 
Other PD biomarkers 
 
7.3.8 
Pediatric Outcomes Data Collection Instrument (PODCI) 
Quality of life will be assessed by completion of the Pediatric Outcomes Data Collection 
Instrument (PODCI).  The subject parent/legal guardians will be asked to complete this 
instrument at the Baseline Day -1, Month 12, and Month 24 Visits. 

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Results will be recorded in the eCRF. 
7.4 
Total Blood Volume Required 
The number and volume of blood samples and total volume of blood to be collected from 
each subject throughout the duration of the 24-month study are summarized in Table 13.  
A total of approximately 104.5-145.5 mL of blood will be collected from each subject 
over the course of the up to 24-month study. 
Table 13 
Blood Sample Number and Volume 
 
Total mL of Blood 
Test 
Day -1a Month 
6 
Month 
9 
Month 
12 
Month 
18 
Month 
21 
Month 
24 
End of 
Dose-
tapering 
Periodb 
Total 
Volume 
Clinical Safety Labsc 
4.5 
4.5 
 
4.5 
4.5 
 
4.5 
4.5 
18-27 
PD Biomarker Panel 
15d 
17e 
 
17e 
17e 
 
17e 
17e 
68-100 
PD Insulin/Glucose/ 
Cortisol 
 
 
5f 
 
 
5f 
 
 
10 
DNA Testing 
 
 
 
 
 
 
8.5 
 
8.5 
Total Volume by Visit 
(mL) 
19.5 
21.5 
5 
21.5 
21.5 
5 
30 
21.5 
104.5-
145.5 
Total Volume: approximately 104.5-145.5 mL 
 a Day -1 blood draws for clinical labs and PD biomarkers will not be repeated for subjects whose Day -1 Visit is 
≤ 28 days following VBP15-003 Week 24 Final Visit and who had blood drawn for clinical labs and PD biomarkers at 
that Visit. 
b Only subjects who participate in the Dose-tapering Period will have bloods drawn. 
c Hematology, Chemistry, Lipids. 
d cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, 
ACTH,and exploratory PD biomarkers.  
e cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, ACTH, 
HbA1c, and exploratory PD biomarkers.  
f Subjects must have fasted ≥ 6 hours prior to blood draws.  Blood will be drawn prior to administration of the dose of 
study medication. 
8 
DATA COLLECTION 
8.1 
Source Documents 
Source documents are defined as original documents, data, and records.  These 
documents may include hospital records, clinical and office charts, laboratory 
data/information, subjects’ diaries or evaluation checklists, pharmacy dispensing and 
other records, recorded data from automated instruments, microfilm or magnetic media, 

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and/or x-rays.  Data collected during this study must be recorded on the appropriate 
source documents. 
A subject enrollment log is to be completed at each study site.  Data recorded on the 
enrollment log are to include a subject identifier, the date of enrollment, and the reason 
the subject was not entered (if applicable).  All subjects initially considered for 
enrollment are to be recorded in this log. 
The investigator(s)/institution(s) will permit study-related monitoring, audits, IRB/IEC 
review, and regulatory inspection(s), providing direct access to source data documents. 
8.2 
Electronic Case Report Form Completion 
Subject data will be collected in this study using an EDC system.  The EDC and database 
system will be OpenClinica by Akaza Research, LLC.  OpenClinica is a web-based 
(https://www.openclinica.com) data entry system utilizing a high security environment.  
The underlying storage facility will be PostgreSQL, whose structure permits the linking 
of subject information across all tables in relational databases.  OpenClinica uses secure 
socket layers (SSL) and in its Enterprise version used in this study is 21 Code of Federal 
Regulations (CFR) Part 11 compliant.  Once an eCRF is created in the database, a data 
dictionary exists and the data team creates compatible paper source documentation. 
The Coordinating Center will design an electronic database in OpenClinica for this study.  
Access rights to the EDC system for the study site team members will need to be 
requested.  Every user of the system will be made aware of the fact that user name and 
password should never be shared and their electronic signature constitutes the legally 
binding equivalent of a hand-written signature.  Only trained personnel certified by the 
Coordinating Center will receive a user name and password. 
All data will be directly entered or collected on a source document and then entered into 
OpenClinica or transferred electronically to the study database (e.g., clinical laboratory 
results, quantitative muscle testing). 
The Coordinating Center data management team will monitor the eCRFs for 
completeness and acceptability throughout the course of the study.  ReveraGen personnel 

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(or their representatives) will be allowed access to all source documents in order to verify 
eCRF entries. 
8.3 
Data Processing 
A clinical study database will be constructed from the eCRFs and any data merged 
electronically, and the data will be validated both manually and electronically.  
Clarification of data will be requested from the study site as required.  The database will 
be quality assured in accordance to the data management plan and will be available for 
statistical analysis according to the methods outlined in Section 9.6 and the Statistical 
Analysis Plan (SAP). 
8.4 
Subject Diaries 
The parent or legal guardian of each subject will be given a subject diary at the Baseline 
Day -1 Visit in which to record any new concomitant medications and any changes to 
existing concomitant medications taken during the study, as well as any AEs experienced 
by the subject during the study.  Parents/legal guardians will be instructed in how to 
record information in the diary and will be instructed to bring the diary with them to each 
study visit for review by study staff for completeness and accuracy.  A new diary will be 
dispensed at each scheduled trimonthly visit for use through the time of the next 
scheduled trimonthly visit; subject diaries dispensed at the Baseline Day -1 Visit will be 
returned at the Month 1 Visit for review by study staff and returned to the subjects for 
continued use through the time of the Month 3 Visit.  Collection of final diaries will 
occur at the Month 24 Visit, or at the end of the Dose-tapering Period for subjects whose 
vamorolone dose is tapered at the end of the study.  The information recorded in the diary 
will be considered source documentation, and any information recorded in the diary 
should be transcribed by study staff to the appropriate eCRF. 
9 
STATISTICAL METHODS AND PLANNED ANALYSES 
Eligible subjects are those who enrolled in the VBP15-003 Phase IIa extension study and 
have completed up to and including the Week 24 final study assessments; up to 
approximately 50 subjects will be enrolled into VBP15-LTE. 

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This is an open-label extension study with no placebo control.  Historical control data are 
available for the same age range (4-10 years), at largely the same study sites, with the 
same outcome measures.  Untreated natural history control population data is from the 
ongoing CINRG DNHS study of ~400 DMD boys.44,45,46,47  Prednisone-treated and 
deflazacort-treated historical control data are from a clinical trial of daily dosing of 
prednisone and deflazacort.48  The vamorolone VBP15-LTE Phase IIa extension trial is 
carried out with daily dosing.   
9.1 
Statistical and Analytical Plan (SAP) 
The sections below summarize the intended statistical methods and analyses for the 
VBP15-LTE extension study.  A more detailed SAP will be written and finalized prior to 
finalization of the clinical study database.  The SAP will give a detailed description of the 
summaries and analyses that will be performed and will clearly describe when these 
analyses will take place.  Any changes to the planned methods and analyses will be 
described and justified in the SAP and/or in the final clinical study report, as appropriate. 
9.1.1 
Deviations from the Statistical Analysis Plan 
An SAP will be written and finalized prior to any lock of the study database.  The SAP 
will give a detailed description of the summaries and analyses that will be performed and 
will clearly describe when these analyses will take place.  Any deviation(s) from the 
original SAP will be described and justified in the clinical study report. 
9.2 
Analysis Populations 
Four populations will be defined for data analysis. 
9.2.1 
Safety Population 
All subjects who receive at least one dose of vamorolone study medication in the 
VBP15-LTE extension study will be included in the Safety Population.  The Safety 
Population is the primary analysis population for safety assessments.  This is also the 
modified Intention to Treat (mITT) population. 

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9.2.2 
Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in the 
VBP15-LTE extension study and have at least one post-baseline assessment will be 
included in the FAS.  The FAS is the primary analysis population for efficacy and PD 
assessments.  The FAS is the mITT population, with the additional requirement of having 
at least one post-baseline assessment.  Subjects who receive at least one dose of 
vamorolone but never have post-baseline assessments will be excluded. 
9.2.3 
Control Population DNHS Study 
The control population from the CINRG Duchenne Natural History Study will include all 
subjects who were observed as part of the study in ages ≥ 4 years and <7 years of age at a 
start of an interval of observation; observed for at least two years with TTSTAND, 
TTCLIMB, TTRW, NSAA, 6MWT and QMT measured; remained glucocorticoid-naive 
during the entire observation period; and were able to walk independently without 
assistive devices, able to complete the TTSTAND; and lacked any history of disease, 
impairment, or medications that would have made them ineligible to receive the 
vamorolone intervention as defined by the VBP15-LTE exclusion criteria at the start of 
the interval.  
9.2.4 
Control Population FOR DMD Study 
The control population from the FOR DMD study will include all subjects who were 4-7 
years old at entry and who were randomized to the daily prednisone or daily deflazacort 
arm.48  
9.3 
Measures Taken to Avoid/Minimize Bias 
Not applicable. 
9.4 
Interim Analysis 
No interim statistical analyses are planned. 

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9.5 
Missing, Unused, and Spurious Data 
The possibility of bias from missing data of subjects who prematurely discontinue will be 
addressed in the clinical study report.  Missing values for safety and exploratory 
outcomes will be treated as missing; while those for efficacy measurements will be 
imputed using methodology as described in the SAP. 
9.6 
Statistical Analysis 
9.6.1 
General Considerations 
Statistical analyses will be performed using SAS®. 
All measurements will be analyzed based upon the type of distribution, and descriptive 
statistics will be presented by treatment group and assessment time point, as appropriate.  
Descriptive statistics for continuous variables (number [N], mean, median, standard 
deviation [SD], minimum, and maximum), descriptive statistics for categorical variables 
(N and percentage), and individual subject profiles will be presented, as appropriate. 
All statistical tests will be performed at the 0.05 level.  Paired t-tests will be utilized for 
select variables.  When available, baseline from the VBP15-002 will be utilized when 
calculating change from baseline. 
9.6.2 
Subject Disposition, Demographics, and Baseline Characteristics 
Subject disposition will be summarized by analysis population.  The number of subjects 
enrolled, the number in each population, and the reason for discontinuation from the 
study will be summarized. 
Subject demographics (e.g., age, race, and ethnicity) and baseline characteristics 
(e.g., height, weight, and months/years since DMD diagnosis) will be summarized 
descriptively by analysis population.   
9.6.3 
Safety Analyses 
All subjects who received at least one dose of vamorolone (Safety Population) will be 
included in the safety analyses.  In general, descriptive statistics for each safety endpoint 

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will be presented by combined vamorolone dose level, individual dose levels, and other 
combinations of dose levels. 
All safety data will be listed. 
Safety data will include BMI (raw units and z-score), height (raw units and z-score), vital 
signs, clinical laboratory test results, spine x-ray results (spine fractures), hand x-ray 
results (bone age), and ECG results.   
Changes in BMI z-score and height z-score will be analyzed using the same type of 
statistical models used for efficacy with vamorolone being compared with the daily 
prednisone and the daily deflazacort arms from the FOR DMD study.  Hand x-ray and 
spine x-ray results will also be compared with the daily prednisone and the daily 
deflazacort arms from the FOR DMD study.   
Adverse events will be summarized overall and by dose level by system organ class 
(SOC) and preferred term (using the Medical Dictionary for Regulatory Activities 
[MedDRA]); by relationship to study medication; and by intensity (CTCAE grade).   
Physical examination results will be listed only. 
9.6.4 
Clinical Efficacy and Pharmacodynamic Analyses 
The evaluations of clinical efficacy and PD will be performed using the FAS Population. 
The primary efficacy outcome is TTSTAND (velocity).  Secondary efficacy outcomes are 
the NSAA assessment, TTCLIMB, TTRW, QMT, and the 6MWT.  TTSTAND, 
TTCLIMB, and TTRW will be analyzed using raw scores and velocity.   
The primary outcome is TTSTAND (velocity) change from VBP15-002 study baseline to 
Month 24 and will be compared between vamorolone and historical untreated controls 
using a restricted maximum likelihood (REML)-based mixed model for repeated 
measures (MMRM).  This model will include fixed effects for treatment, visit, baseline 
TTSTAND velocity (from the VBP15-002 study), age at study entry, and the treatment-
by-visit interaction.  The initial model will compare combined vamorolone doses to 
untreated natural history controls and subsequent secondary models may compare 
individual and other combinations of dose levels to untreated natural history controls.  

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The secondary outcome measures will be compared using similar models.  Full details 
will be provided in the Statistical Analysis Plan (SAP).   
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover 
will be assessed, as well as exploratory biomarkers of safety and efficacy.  Biomarkers 
will be summarized descriptively over time. 
Individual clinical efficacy and PD data will be listed. 
9.6.5 
Concurrent Medications 
A summary of all concomitant medications taken during the course of the study will be 
presented in tabular form by therapeutic drug class and generic drug name using the 
World Health Organization (WHO) Drug classification (Version 4.3).  All concomitant 
medications will be detailed in the subject data listings. 
10 
STUDY MANAGEMENT AND ETHICAL AND REGULATORY 
REQUIREMENTS 
10.1 
Regulatory Approval and Good Clinical Practice 
This study will be conducted in accordance with the principles of the 18th World Medical 
Assembly (Helsinki, June 1964), and amendments of the 29th (Tokyo, 1975), 35th 
(Venice, 1983), 41st (Hong Kong, 1989), 48th (Somerset West, 1996), 52nd (Edinburgh, 
2000), 53rd (Washington, 2002), 55th (Tokyo, 2004), 59th (Seoul, 2008), and 64th 
(Fortaleza, 2013) World Medical Assemblies. 
Further, the trial will be conducted in accordance with: 
• International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical 
Practice (GCP) 
• The United States (US) FDA Code of Federal Regulations, Title 21 CFR Part 312 
– Investigational New Drug Application, Part 50 – Protection of Human Patients 
with particular focus in SubPart D, and/or Part 56 – Institutional Review Boards 
• US Health Insurance Portability and Accountability Act of 1996 (HIPAA). 

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10.2 
Investigator Responsibilities 
10.2.1 
Subject Information and Informed Consent 
Before being admitted to the VBP15-LTE extension study, a parent/guardian must 
consent in writing for the subject to participate.  Written or verbal assent will also be 
obtained from each subject as required per regulations.  An approved ICF will be given to 
each parent/guardian which will contain all US federally required elements, all 
ICH-required elements, and HIPAA authorization information, if applicable, in language 
that is understandable to the parent/guardian.  The consent should note that the 
Investigator is receiving compensation for the expenses of conducting the study. 
The process of obtaining the informed consent will be in compliance with all federal 
regulations, ICH requirements, and local laws. 
The Investigator or designee will review the study with the parent/guardian of each 
subject.  The review will include the nature, scope, procedures, and possible 
consequences of the subject’s participation in the study.  The consent, assent, and review 
must be in a form understandable to the parent/guardian of the subject.  The Investigator 
or designee and the parent/guardian of the subject must both sign and date the ICF after 
review and before the subject can participate in the study.  The parent/guardian of the 
subject will receive a copy of the signed and dated form, and the original will be retained 
in the site study files.  The Investigator or designee must emphasize to the 
parent/guardian of the subject that study participation is entirely voluntary and that 
consent regarding study participation may be withdrawn at any time without penalty or 
loss of benefits to which the subject is otherwise entitled. 
If the ICF is amended during the study, the Investigator must follow all applicable 
regulatory requirements pertaining to all new subjects and repeat the consent process with 
the amended ICF for any ongoing subjects. 

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10.2.2 
Institutional Review Board/Independent Ethics Committee Approval and 
Other Institutional Requirements 
Before the start of the study, the study protocol, ICF, and any other appropriate 
documents will be submitted to the IRB/IEC for review and approval.  Per institutional 
requirements, the study protocol and any other appropriate documents will be submitted 
to scientific committees for approval. 
The Investigator will forward to the Sponsor, or designee (Coordinating Center), a copy 
of the IRB/IEC’s approval of this protocol, amendments, ICF and any changes to the ICF, 
based on the FDA regulations set forth in Part 56 of Title 21 of the CFR.  The 
Investigator will also keep documentation of study approval by internal scientific 
committees per institutional requirements. 
Study medication can only be supplied to the Investigator after documentation of all 
ethical and legal requirements for starting the study has been received by the Sponsor or 
designee (Coordinating Center).  This documentation must also include an IRB/IEC 
membership list that contains members’ occupations and qualifications.  If the IRB/IEC 
will not disclose the names of the committee members, it should be asked to issue a 
statement confirming that the composition of the committee is in accordance with GCP.  
The IRB Assurance Number may be accepted as a substitute for the IRB membership list. 
The Investigator will keep the IRB/IEC informed regarding the progress of the study, per 
institutional requirements.  No changes will be made in the study without IRB/IEC 
approval, except when required to eliminate apparent immediate hazards to the subjects. 
While the study is ongoing and at study completion/discontinuation, the Investigator must 
submit to the IRB/IEC the following information in accordance with US Federal 
regulatory requirements: 
1. Information on serious or unexpected AEs, showing due diligence in providing 
this information as soon as possible 
2. Periodic reports on the progress of the study 
3. Final Study Summary upon study completion or closure. 

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Notification of the end of the trial will be sent to the IRB/IEC within 30 days after 
completion of the study close-out visit.  In case the study is ended prematurely, the 
IRB/IEC will be notified within 15 days, including the reasons for the premature 
termination.  The end of the trial is defined as the date of final analysis of the study data 
according to the SAP. 
10.2.3 
Study Documentation 
10.2.3.1 
Before the Start of the Study 
The following study documentation will be in place at the study site prior to the first 
administration of study drug: 
• 
Fully signed protocol and protocol-supporting manuals 
• 
Investigator’s Brochure29 
• 
Protocol Acceptance form signed by the Investigator 
• 
IRB/IEC-approved copy of the ICF 
• 
Curriculum vitae of the Investigator and all sub-investigators listed on the FDA 
Form 1572 
• 
A letter of IRB/IEC approval for protocol 
• 
A list of members of the IRB/IEC and their affiliations 
• 
A copy of the Investigator-signed FDA 1572 form 
• 
An Investigator-signed financial disclosure form. 
10.2.3.2 
During the Study 
The following documentation should be added to the site study file during study conduct: 
• 
Any paper source forms completed and subsequently entered into the study 
database.  An explanation should be given for all missing data and any protocol 
deviations documented in the site study file 
• 
Any changes to the documentation identified above in Section 10.2.3.1 
• 
Shipping documents relating to shipment of medication (drug accountability) and 
bioanalytical samples 

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• 
Copies of relevant correspondence such as letters, emails, meeting notes, and 
telephone calls. 
10.2.3.3 
After the Study 
After completion or premature termination of the trial, all of the documents identified 
should be in the file, together with the following: 
• Study drug accountability documents 
• Audit certificates (if applicable) 
• Investigator delegation of responsibilities log 
• Site signature log 
• Subject enrollment log 
• Substantive correspondence with the Sponsor and IRB/IEC 
• Notification of the end of the trial to the IRB/IEC. 
10.2.4 
Delegation of Investigator Responsibilities 
The Investigator must (a) ensure that any individual to whom a task is delegated is 
qualified by education, training, and experience (and licensure, if relevant) to perform the 
task; and (b) provide adequate supervision.  The Investigator should maintain a list of 
sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties. 
10.3 
Protocol Deviations and Violations 
10.3.1 
Protocol Deviation and Violation Definitions 
10.3.1.1 
Protocol Deviation 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that is under the Investigator’s control and that has not 
been approved by the IRB/IEC. 
Changes or alterations in the conduct of the trial which do not have a major impact on the 
subject's rights, safety or well-being, or the completeness, accuracy and reliability of the 
study data are considered minor protocol deviations. 

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10.3.1.2 
Protocol Violation 
A protocol violation is a deviation from the IRB/IEC-approved protocol that may affect 
the subject's rights, safety, or well-being and/or the completeness, accuracy and reliability 
of the study data. This includes examples such as inappropriate consent, errors in drug 
dosing, or lack of reporting of safety data. 
10.3.2 
Reporting Deviations/Violations 
Upon discovery of a major protocol deviation or violation, the Investigator is responsible 
for reporting protocol deviations or violations to the IRB/IEC and Sponsor or designee 
(Coordinating Center) within 24 hours of discovery. 
All other deviations must be reported in writing within 7 days of the event or its 
discovery. 
10.4 
Study Records Retention and Direct Access to Source Documents 
Federal regulations require that, following completion of a clinical study, a copy of all 
records of that study be maintained by the Investigator for at least the shorter of the 
following two time periods: 
• Two years after FDA approval of the drug for the indication for which it was 
investigated, or 
• In situations where no application is to be submitted or an application is not 
approved for such indication, 2 years after the Investigational New Drug (IND) 
Application is discontinued and the FDA is notified. 
The Investigator must maintain a copy of all data collected for each subject treated 
(including eCRFs and source data).  In order to assure the accuracy of data collected in 
the eCRF, it is mandatory that representatives of the Sponsor, or designee, as well as 
representatives of the FDA or other health authorities have direct access to original 
source documents (e.g., subject records, subject charts, and laboratory reports).  During 
the review of these documents, the anonymity of the subject will be respected with strict 
adherence to professional standards of confidentiality. 

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The Sponsor reserves the right to terminate the study for refusal of the Investigator to 
supply source documentation of work performed in this clinical study. 
The following includes, but is not limited to, the records that must be retained by the 
Investigator: 
1. Signed informed consent documents for all subjects 
2. Subject enrollment log 
3. Record of all relevant communications between the Investigator and the IRB/IEC 
4. Composition of the IRB/IEC 
5. Record of all relevant communications between the Investigator and the Sponsor 
(or designee) 
6. List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their 
roles in the study and their signatures 
7. Drug accountability records (see Section 5.8.4) 
8. Record of any body fluids or tissue samples retained 
9. All other source documents (subject records, hospital records, laboratory records, 
etc.) 
10. All other documents as listed in Section 8 of the ICH consolidated guideline on 
GCP (Essential Documents for the Conduct of a Clinical Trial). 
10.5 
Data and Safety Monitoring Board (DSMB) and Other Study Monitoring 
10.5.1 
DSMB 
An unblinded Data and Safety Monitoring Board (DSMB), operating autonomously from 
the Sponsor and the site investigators, will be responsible for providing independent 
recommendations to the Sponsor about risk-benefit of the study and for any modification 
affecting safety or data integrity required during the course of the study.  The DSMB 
members must not be actively involved in study design, conduct or daily management of 
this study and must not have financial, proprietary, professional, or other interests that 
may affect impartial, independent decision-making.  

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Specialists may be invited to participate as non-voting members at any time if additional 
expertise is desired.  The DSMB will formally interact with the Sponsor through the 
sharing of DSMB meeting minutes.  
The DSMB will be responsible for: 
• 
Examining accumulating safety and other relevant data at pre-specified points 
during the course of the study in order to make recommendations concerning 
continuation, termination, or modification of the study; 
• 
Examining accumulating clinical efficacy data and comparing to corticosteroids 
and an untreated historical control group in order to make recommendations 
concerning continuation, termination, or modification of the study; 
• 
Reviewing protocol violations; 
• 
Providing expert advice to the Sponsor on an ad hoc basis regarding matters such 
as safety concerns or diagnostic evaluations in individual subjects; 
• 
Based on the results of its deliberations, the DSMB can recommend continuation 
of the study unchanged, study interruption, study termination, modification of the 
studies, or alteration in the DSMB monitoring plan. 
10.5.2 
Study Monitoring 
In accordance with applicable regulations, GCP, and the procedures of the Sponsor or its 
designees, the Study Monitor will periodically contact the site and conduct on-site visits.  
The extent, nature, and frequency of on-site visits will be based on enrollment rate and 
data quality at the site.  Through frequent communications (e.g., letter, e-mail, and 
telephone), the Study Monitor will ensure that the investigation is conducted according to 
protocol and regulatory requirements. 
During these contacts, the monitoring activities will include: 
1. Checking and assessing the progress of the study 
2. Reviewing study data collected to date for completeness and accuracy 
3. Reviewing compliance with protocol assessments 

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4. Conducting source document verification by reviewing eCRF database data 
against source documents when available (e.g., medical records, subject diaries, 
ICF [and assent, if applicable], laboratory result reports, raw data collection 
forms) 
5. Identifying any issues and addressing resolutions. 
These activities will be done in order to verify that the: 
1. Data are authentic, accurate, and complete 
2. Safety and rights of the subjects are being protected 
3. Study is conducted in accordance with the currently approved protocol (and any 
amendments), GCP, and all applicable regulatory requirements. 
The Investigator will allow the Study Monitor direct access to all relevant documents, 
and allocate his/her time and the time of his/her staff to the Study Monitor to discuss 
findings and any relevant issues. 
In addition to contacts during the study, the Study Monitor will contact the site prior to 
the start of the study to discuss the protocol and data collection procedures with site 
personnel. 
At study closure, Study Monitors will conduct all activities as indicated in Section 10.7. 
10.6 
Quality Assurance 
At its discretion, the Sponsor or its designee may conduct a quality assurance audit of this 
study.  Auditing procedures of the Sponsor and/or its designee will be followed in order 
to comply with GCP guidelines and ensure acceptability of the study data for registration 
purposes.  If such an audit occurs, the Investigator will give the auditor direct access to 
all relevant documents, and will allocate his/her time and the time of his/her staff to the 
auditor as may be required to discuss findings and any relevant issues. 
In addition, regulatory authorities and/or the IRB/IEC may conduct an inspection of this 
study.  If such an inspection occurs, the Investigator will allow the inspector direct access 
to all source documents, eCRFs, and other study documentation for source data check 

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and/or on-site audit inspection.  The Investigator must allocate his/her time and the time 
of his/her staff to the inspector to discuss findings of any relevant issues. 
An explanation will be given for all missing, unused, and spurious data in the relevant 
section of the study report. 
10.7 
Study Termination and Site Closure 
Upon completion of the study, the following activities, when applicable, must be 
conducted by the Study Monitor in conjunction with the Investigator, as appropriate: 
1. Provision of all study data to the Sponsor 
2. Data clarifications and/or resolutions 
3. Accounting, reconciliation, and final disposition of used and unused study 
medication 
4. Review of site study records for completeness. 
In addition, the Sponsor reserves the right to temporarily suspend or prematurely 
terminate this study for any reason. 
If the study is suspended or terminated for safety reason(s), the Sponsor will promptly 
inform the Investigator, and will also inform the regulatory authorities of the suspension 
or termination of the study and the reason(s) for the action.  The Investigator is 
responsible for promptly informing the IRB/IEC, and providing the reason(s) for the 
suspension or termination of the study. 
If the study is prematurely terminated, all study data must be returned to the Sponsor.  In 
addition, the site must conduct final disposition of all unused study medications in 
accordance with the Sponsor procedures for the study. 
10.8 
Site Termination 
The Sponsor may at any time, at its sole discretion, terminate the study site for various 
reasons, including, without limitation, the following: 
1. Failure of the Investigator to enroll subjects into the study at a reasonable rate 
2. Failure of the Investigator to comply with applicable laws and/or pertinent FDA 
regulations 

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3. Submission of knowingly false information from the research facility to the 
Sponsor, Study Monitor, FDA, or other regulatory authorities 
4. Insufficient adherence to protocol requirements. 
If participation of a study site is terminated, the Sponsor and Study Chair will issue a 
written notice to the Investigator.  The written notice will contain the reasons for taking 
such action.  If the study site is terminated for noncompliance, appropriate regulatory 
authorities will also be notified by the Sponsor. 
Study termination and follow-up will be performed in compliance with the conditions set 
forth in 21 CFR 312.50 and 21 CFR 312.56. 
10.9 
Discontinuation of Study 
The Sponsor reserves the right to discontinue the study for any reason at any time.  In 
addition, the study may be stopped at any time if, in the opinion of the Sponsor and 
Medical Monitor, safety data suggest that the medical safety of subjects is being or may 
become compromised. 
11 
DISCLOSURE OF DATA 
11.1 
Confidentiality 
The rights and privacy of participants in this study will be protected at all times.  All 
personal details of subjects will be treated as confidential by the Investigator and 
handling of personal data will be in compliance with HIPAA.  All applicable data 
protection laws in the relevant countries will be adhered to at all times. 
Subject names will remain confidential and will not be included in the database.  Only 
enrollment number and birth date will be recorded on the eCRF.  If the subject’s name 
appears on any other document collected (e.g., hospital discharge summary), the name 
must be obliterated before the document is transmitted to the Sponsor or its designee.  All 
study findings will be stored in electronic databases.  The subjects’ parents or guardians 
will give explicit permission for representatives of the Sponsor, regulatory authorities, 
and the IRB/IEC to inspect the subjects’ medical records to verify the information 
collected.  The subjects’ parents or guardians will be informed that all personal 

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information made available for inspection will be handled in the strictest confidence and 
in accordance with all state, local, and federal data protection/privacy laws, including, 
without limitation, the HIPAA, as applicable. 
The parents or guardians of all participants in the United States will provide written 
authorization to disclose private health information either as a part of the written ICF or 
as a separate authorization form.  The authorization will contain all required elements 
specified by 21 CFR 50, and will contain a waiver of subject access to study-related 
private health information until the conclusion of the clinical study.  The authorization 
will remain valid and in full force and effect until the first to occur of (1) the expiration of 
2 years after the study medication is approved for the indication being studied, or (2) the 
expiration of 2 years after the research program is discontinued.  Individual subject 
medical information obtained during this study is confidential, and its disclosure to third 
parties (other than those mentioned in this section) is strictly prohibited.  In addition, 
medical information obtained during this study may be provided to the subject’s personal 
physician or to other appropriate medical personnel when required in connection with the 
subject’s continued health and welfare. 
The study Investigator will maintain a subject identification log (enrollment numbers and 
corresponding subject names) to enable records to be identified. 
Study data will be shared with the study ‘Use of Microsoft Bands as an Outcome 
Measure in Boys with DMD - Parallel study to Clinical Study Protocol VBP15-003’ if 
the subject’s parent/legal guardian consents for his participation in both studies. 
11.2 
Publication 
ReveraGen BioPharma, Inc. retains the ownership of all data and results collected during 
this study.  Therefore, the Sponsor reserves the right to use the data from this present 
study, either in the form of eCRFs (or copies of these), or in the form of a report, with or 
without comments and analysis in order to submit them to the US FDA or the Health 
Authorities of any country. 
Furthermore, in the event that the clinical research leads to patentable results, the 
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refrain from filing patent application(s).  Patent applications will be filed by ReveraGen 
BioPharma, Inc. or another entity delegated by ReveraGen BioPharma, Inc. 
All information concerning the product as well as any information such as clinical 
indications for the drug, its formula, methods of manufacture and other scientific data 
relating to it, that have been provided by the Sponsor or designee, and are unpublished, 
are confidential and must remain the sole property of the Sponsor.  The Investigator will 
agree to use the information only for the purposes of carrying out this study and for no 
other purpose unless prior written permission from the Sponsor is obtained.  The Sponsor 
has full ownership of the eCRFs completed as part of the study. 
By signing the study protocol, the Investigator agrees that the results of the study may be 
used for the purposes of national and international registration, publication, and 
information for medical and pharmaceutical professionals by the Sponsor.  If necessary, 
the authorities will be notified of the Investigator's name, address, qualifications, and 
extent of involvement. 
The Sponsor or designee will prepare a final report on the study.  The Investigator may 
not publish or present any information on this study without the express written approval 
of the Sponsor.  Additionally, the Sponsor, may, for any reason, withhold approval for 
publication or presentation. 
12 
INVESTIGATOR’S PROTOCOL AGREEMENT 
The Investigator's Protocol Agreement at the front of this document must be signed by 
the study site Principal Investigator.  The original or a copy must be kept on file by the 
Sponsor and the Investigator must retain the original or a copy.  The completed Protocol 
Agreement signifies review and acceptance of the protocol by the Principal Investigator 
prior to initiation of the study. 

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13 
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33. Larson CM and Henderson RC. Bone mineral density and fractures in boys with 
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34. McDonald DG, Kinali M, Gallagher AC, et al. Fracture prevalence in Duchenne 
muscular dystrophy. Developmental Medicine and Child Neurolog. 2002; 44: 695-
8. 
35. King WM, Ruttencutter R, Nagaraja HN, et al. Orthopedic outcomes of long-term 
daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology, 2007; 
68: 1607-13. 
36. Cummings EA, Ma J, Fernandez CV, et al. Incident vertebral fractures in children 
with leukemia during the four years following diagnosis. J Clin Endocrinol Metab, 
2015; 100: 3408-17. 
37. Rodd C, Lang B, Ramsay T, et al. Incident vertebral fractures among children with 
rheumatic disorders 12 months after glucocorticoid initiation: a national 
observational study. Arthritis care & research. 2012; 64: 122-31. 
38. Medeiros MO, Behrend C, King W, Sanders J, Kissel J, Ciafaloni E. Fat embolism 
syndrome in patients with Duchenne muscular dystrophy. Neurology. 2013; 80: 
1350-2. 
39. McAdam LC, Rastogi A, Macleod K, Douglas Biggar W. Fat Embolism Syndrome 
following minor trauma in Duchenne muscular dystrophy. Neuromuscul Disord. 
2012; 22: 1035-9. 
40. Gordon KE, Dooley JM, Sheppard KM, MacSween J, Esser MJ. Impact of 
bisphosphonates on survival for patients with Duchenne muscular dystrophy. 
Pediatrics. 2011; 127: e353-8. 
41. Fleishaker DL, Mukherjee A, Whaley FS, Daniel S, Zeiher BG. Safety and 
pharmacodynamic dose response of short-term prednisone in healthy adult 
subjects: a dose ranging, randomized, placebo-controlled, crossover study. BMC 
Musculoskelet Disord. 2016 Jul 16;17:293. 
42. Hathout Y, Brody E, Clemens PR, et al. Large-scale serum protein biomarker 
discovery in Duchenne muscular dystrophy. Proc Natl Acad Sci USA. 2015; 
112(23): 7153-8. 
43. Conklin LS, Damsker JM, Hoffman EP, et al. Phase IIa trial in Duchenne muscular 
dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-
inflammatory drug. Pharmacol. Res. 2018 Sep 13; 136:140-50. 

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44. Bello L, Kesari A, Gordish-Dressman H, et al. Genetic modifiers of ambulation in 
the Cooperative International Neuromuscular Research Group Duchenne natural 
history study. Ann Neurol. 2015; 77(4):684-696. 
45. Spurney C, Shimizu R, Morgenroth LP, et al. Cooperative International 
Neuromuscular Research Group Duchenne Natural History Study demonstrates 
insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular 
dystrophy. Muscle Nerve. 2014; Aug;50(2):250-256.  
46. McDonald CM, Henricson EK, Abresch RT, et al. The Cooperative International 
Neuromuscular Research Group Duchenne natural history study – a longitudinal 
investigation in the era of glucocorticoid therapy: design of protocol and the 
methods used. Muscle Nerve. 2013; 48(1):32-54.  
47. Henricson EK, Abresch RT, Cnaan A, et al. The Cooperative International 
Neuromuscular Research Group Duchenne natural history study: glucocorticoid 
treatment preserves clinically meaningful function milestones and reduces rate of 
disease progression as measured by manual muscle testing and other commonly 
used clinical trial outcome measures. Muscle Nerve. 2013; 48(1):55-67. 
48. Guglieri M, Bushby K, McDermott MP, et al. Developing standardized 
corticosteroid treatment for Duchenne muscular dystrophy. Contempt. Clin. Trials. 
2017 Jul; 58:34-39. 
49. FDA Draft Guidance for Industry: Duchenne muscular dystrophy and related 
dystrophinopathies: developing drugs for treatment. June 2015. 
50. Brooke MH, Griggs RC, Mendell JR, et al. Clinical trial in Duchenne dystrophy. I. 
The design of the protocol. Muscle & Nerve. 1981; 4(3): 186-97. 
51. Mazzone ES, Messina S, Vasco G, et al. Reliability of the North Star Ambulatory 
Assessment in a multicentric setting. Neuromuscul Disord. 2009; 19(7): 458-61. 
52. McDonald CM, Henricson EK, Han JJ, et al. The 6-minute Walk Test as a new 
outcome measure in Duchenne muscular dystrophy. Muscle Nerve. 2010; 41(4): 
500-10.  
53. Mayhew JE, Florence JM, Mayhew TP, et al. Reliable surrogate outcome measures 
in multicenter clinical trials of Duchenne muscular dystrophy. Muscle Nerve. 
2007; 35(1): 36-42. 
 

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14 
APPENDICES 
 

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Appendix 14.1 
Vamorolone Dose Calculation Worksheet and Bulk Dispensing 
Guide 
Vamorolone is administered once daily as a 4% oral suspension.  The volume per dose is 
determined by the subject’s dosing level and body weight (in kg) at each study 
medication dispensing visit, as shown by Equation 1: 
Equation 1 
Subject Weight (kg) x Dose Level (mg/kg) 
= Subject Dose (in mL) 
40 mg/mL 
Subject weight (in kg) should be rounded to the nearest whole integer for the calculation 
of volume per dose. 
Calculated dose volume will be rounded to the nearest 0.01 mL (1 mL syringe), 0.1 mL 
(3 mL syringe), or 0.2 mL (5 mL syringe), depending upon the total dose volume and 
calibration of the volumetric syringe to be used for administration of dose, as shown in 
the examples below: 
Example 1: Dose volume calculation for a subject receiving 0.25 mg/kg/day with a body 
weight of 27 kg:  
Subject Weight (27 kg) x  Dose Level (0.25 mg/kg) 
= 0.169 mL 
40 mg/mL 
The subject will receive a daily dose volume of 0.169 mL per dose throughout the period 
until the next scheduled visit.  Dose will be administered using a 1 mL volumetric syringe 
rounded to the nearest 0.01 mL, or 0.17 mL daily. 
Example 2: Dose volume calculation for a subject receiving 6.0 mg/kg/day with a body 
weight of 23 kg:  
Subject Weight (23 kg) x Dose Level (6.0 mg/kg) 
= 3.45 mL 
40 mg/mL 
The subject will receive a daily dose volume of 3.45 mL per dose throughout the period until 
the next scheduled visit.  Dose will be administered using a 5 mL volumetric syringe rounded 
to the nearest 0.2 mL, or 3.4 mL daily. 
 
Vamorolone 4% Suspension Dispensing Guide 
Each subject enrolled in the study will be dispensed 100 ml bottle(s) of vamorolone 4% 
suspension at the Baseline Day -1 Visit, sufficient for dosing through the time of the next 

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scheduled trimonthly visit.  Additional supplies will be dispensed at each scheduled 
trimonthly visit, through Month 24.  Subjects whose vamorolone dose is tapered during 
the Dose-tapering Period will be dispensed additional vamorolone 4% suspension at the 
Month 24 Visit, sufficient for dose tapering to 0 mg/kg/day (see Section 6.3.4). 
The number of bottles to be dispensed at each dispensing visit for the following 3-month 
dosing period until the next scheduled trimonthly visit is calculated by multiplying the 
subject’s daily dose (in mL/day) (as calculated by Equation 1) by 100 days (93 days in 
the dosing period + 7 days overage) and dividing that number by 100 mL, the number of 
mL per bottle, as shown in Equation 2, below: 
Equation 2 
Daily Dose (mL/day) x 100 Days 
= #Bottles to be Dispensed 
for 3 months dosing 
100 mL 
 
Example 3: Calculation of number of bottles to be dispensed for 3-month dosing for a 
subject taking a daily dose of 0.17 mL (from Example 1 above): 
Daily Dose (0.17 mL/day) x 100 Days 
= 0.17 Bottles 
100 mL 
The number of bottles dispensed is rounded to the nearest whole integer, or 1 bottle to be 
dispensed. 
Example 4: Calculation of number of bottles to be dispensed for 3-month dosing for a 
subject taking a daily dose of 3.4 mL (from Example 2 above):  
Daily Dose (3.45 mL/day) x 100 Days 
= 3.45 Bottles 
100 mL 
The number of bottles dispensed is rounded to the nearest whole integer, or 4 bottles to be 
dispensed. 
Each bulk bottle should be used for one subject only.  Each bottle dispensed to the 
subject and ready for administration to subjects will be labeled with subject number, 
dispense date, protocol number, dose level, and volume to be administered per dose. 
Any unused or partially used drug product should be returned at each scheduled 
trimonthly visit through Month 24 and at the end of the Dose-tapering Period, if 

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applicable, and retained at the clinical study site for investigational drug accountability 
monitoring. 
 
 

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Appendix 14.2 
Protocol Amendment #1 Complete List of Changes 
The following changes have been incorporated into the protocol under this protocol 
amendment, as summarized in Protocol Amendment Tracking, Reasons for Protocol 
Amendment #1.  Protocol sections that have been changed are itemized below with the 
original and revised text.  Changes that were strictly editorial (e.g. punctuation, correction 
of spelling errors, grammar) are not included. 
Section Changed: 
Synopsis, Study Period 
Original Text: 
Study Period 
First subject enrolled: 1Q 2017 
Last subject last visit: 1Q 2021 
 
Revised Text: 
Study Period 
First subject enrolled: 1Q 2017 
Last subject last visit: 2Q 2020 
 
Section Changed: 
Synopsis, Study Summary 
Paragraph 7 
Original Text: 
In the event any clinical observation suggests an intolerability for an individual subject to the study 
medication, in the opinion of the Investigator, the subject’s dose level may be decreased to the next lower 
dose level (e.g., a subject taking 6.0 mg/kg/day may be decreased to 2.0 mg/kg/day) and maintained at that 
lower dose level throughout the duration of the Treatment Period.  In the event the next lower dose level is 
also not tolerated and is considered a safety risk to the subject, in the opinion of the Investigator, Study 
Chair, and Medical Monitor, the subject will be withdrawn from the study. 
Revised Text: 
In the event any clinical observation suggests an intolerability for an individual subject to the study 
medication, in the opinion of the Investigator, the subject’s dose level may be decreased to the next lower 
dose level and maintained at that lower dose level throughout the duration of the Treatment Period, with the 
caveat stated below for subjects de-escalating from 6.0 mg/kg/day to 2.0 mg/kg/day.  In the event the next 
lower dose level is also not tolerated and is considered a safety risk to the subject, in the opinion of the 
Investigator, Study Chair, and Medical Monitor, the subject will be withdrawn from the study.  Subjects 
whose dose is decreased from 6.0 mg/kg/day to 2.0 mg/kg/day may have their dose subsequently increased 

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to 4.0 mg/kg/day if they have been taking the 2.0 mg/kg/day dose for at least one month and, in the opinion 
of the Investigator, balancing efficacy with safety concerns, they could benefit from an intermediate higher 
dose.   
Section Changed: 
Synopsis, Safety Measures 
Bullets #3 and #7 
Original Text: 
• 
Weight 
• 
Body Mass Index (BMI) 
 
• 
12-lead electrocardiogram (ECG) 
• 
Clinical signs and symptoms (AEs and SAEs) 
Revised Text: 
• 
Weight 
• 
Height 
• 
Body Mass Index (BMI) 
 
• 
12-lead electrocardiogram (ECG) 
• 
Hand x-ray 
• 
Spine x-ray 
• 
Clinical signs and symptoms (AEs and SAEs) 
Section Changed: 
Synopsis, Exploratory Measures 
Original Text: 
• 
Measures of serum proteins (SomaSCAN aptamer panel; proteomics profiling; steroid hormones; other 
biomarkers) 
• 
Quality of life (PODCI)  
Revised Text: 
• 
Measures of serum PD biomarkers 
• 
Quality of life (PODCI)  
• 
DNA testing for established genetic modifiers of DMD 

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Section Changed: 
Synopsis, Statistical Methods 
Original Text: 
Analysis Populations: 
All analyses will be based on the actual treatment each subject received.  Four populations will be defined 
for data analysis: the Safety Population, the Full Analysis Set, the control population CINRG Duchenne 
Natural History Study, and the control population CINRG Prednisone study. 
Safety Population 
All subjects who receive at least one dose of vamorolone study medication in the VBP15-LTE extension 
study will be included in the Safety Population.  The Safety Population is the primary analysis population 
for safety assessments.  This is also the modified Intention to Treat (mITT) population. 
Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in the extension study and have 
at least one post-baseline assessment will be included in the FAS.  The FAS is the primary analysis 
population for clinical efficacy and PD assessments.  The FAS population is the mITT population, with the 
additional requirement of having at least one post-baseline assessment.  Subjects who receive at least one 
dose of vamorolone but never have post-baseline assessments will be excluded. 
Control Populations from CINRG Duchenne Natural History Study  
The control population from the CINRG Duchenne Natural History Study will include all subjects who 
were observed as part of the study in ages ≥ 4 years and <7 years of age at a start of an interval of 
observation; observed for at least one year with at least two visits in a time interval of no more than 15 
months with TTSTAND, TTCLIMB, TTRW, NSAA, 6MWT and QMT measured; remained 
glucocorticoid-naive during the entire observation period; and were able to walk independently without 
assistive devices, able to complete the TTSTAND; and lacked any history of disease, impairment, or 
medications that would have made them ineligible to receive the vamorolone intervention as defined by the 
Phase IIa extension study VBP15-LTE exclusion criteria at the start of the interval. 
Control Population CINRG Prednisone Study 
The control population from the CINRG Prednisone study will include all subjects who were younger than 
7 years old at entry and who were randomized to the daily prednisone arm. 
General Statistical Considerations: 
All measurements will be analyzed based upon the type of distribution and descriptive statistics presented 
by treatment group and time point, as appropriate.  No interim statistical analyses are planned.  Missing 
values for safety and exploratory outcomes will be treated as missing. 
Baseline measurement is defined as the last non-missing value prior to the first dose of study drug in the 
extension study. 
Efficacy Analyses: 
The primary efficacy outcome is TTSTAND.  Secondary efficacy outcomes are the NSAA assessment, 
TTCLIMB, TTRW, QMT, and the 6MWT.  The primary outcome will be compared between vamorolone 
and historical untreated controls using a mixed-effects linear model with treatment group.  Age at study 
entry will be included as a covariate.  The initial model will compare combined vamorolone doses to 
untreated natural history controls and a subsequent secondary model will compare each dose to untreated 
natural history controls.  This will allow the testing of whether vamorolone in general and vamorolone at 
individual doses have significant effects on the slope of the velocity.  Additional hypotheses of efficacy 
will include similar linear modelling with the secondary outcomes.  They will also include comparison 
groups including prednisone-treated or untreated natural history controls. 

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Pharmacodynamics Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover will be assessed, as 
well as exploratory biomarkers of safety and efficacy.  Longitudinal analysis of PD biomarkers will be 
studied as a function of treatment, with comparison to prednisone-treated and untreated historical controls, 
as appropriate. 
Safety Analyses: 
All evaluations of clinical safety will be listed with descriptive statistics by treatment group presented.  The 
primary safety variable will be BMI z-score and will be assessed using the same type of statistical models 
used for efficacy.  Additional secondary safety data will include height z-score, blood pressure, and ECG 
results.  As no change in blood pressure or cardiac results is expected, these data will be analyzed using an 
analysis of covariance (ANCOVA) approach which includes the baseline value for each measurement as a 
covariate.  Changes in height z-scores, for which an observed change is expected, will be modelled using a 
linear mixed effects model.  Continuous, quantitative laboratory values will be analyzed similar to BMI 
z-scores.  Categorized laboratory values and presence or absence of AEs will be compared using an exact 
chi-square test.  Adverse events will be summarized overall and by dose level, system organ class (SOC) 
and preferred term (using the Medical Dictionary for Regulatory Activities [MedDRA]); by dose level and 
relationship to study medication; and by dose level and intensity (CTCAE grade).  Additional hypotheses 
of safety will include similar linear modelling with the secondary and exploratory outcomes. 
Revised Text: 
Analysis Populations: 
Four populations will be defined for data analysis: the Safety Population, the Full Analysis Set, the control 
population CINRG Duchenne Natural History Study, and the control population FOR DMD Study. 
Safety Population 
All subjects who receive at least one dose of vamorolone study medication in the VBP15-LTE extension 
study will be included in the Safety Population.  The Safety Population is the primary analysis population 
for safety assessments.  This is also the modified Intention to Treat (mITT) population. 
Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in the VBP15-LTE extension 
study and have at least one post-baseline assessment will be included in the FAS.  The FAS is the primary 
analysis population for clinical efficacy and PD assessments.  The FAS population is the mITT population, 
with the additional requirement of having at least one post-baseline assessment.  Subjects who receive at 
least one dose of vamorolone but never have post-baseline assessments will be excluded. 
Control Population from CINRG Duchenne Natural History Study  
The control population from the CINRG Duchenne Natural History Study will include all subjects who 
were observed as part of the study in ages ≥ 4 years and <7 years of age at a start of an interval of 
observation; observed for at least two years with TTSTAND, TTCLIMB, TTRW, NSAA, 6MWT and 
QMT measured; remained glucocorticoid-naive during the entire observation period; and were able to walk 
independently without assistive devices, able to complete the TTSTAND; and lacked any history of 
disease, impairment, or medications that would have made them ineligible to receive the vamorolone 
intervention as defined by the VBP15-LTE exclusion criteria at the start of the interval. 
Control Population FOR DMD Study 
The control population from the FOR DMD Study will include all subjects who were 4-7 years old at entry 
and who were randomized to the daily prednisone or daily deflazacort arm. 
General Statistical Considerations: 
All measurements will be analyzed based upon the type of distribution and descriptive statistics presented 
by treatment group and time point, as appropriate.  No interim statistical analyses are planned.  Missing 
values for safety and exploratory outcomes will be treated as missing. 
All statistical tests will be performed at the 0.05 level.  Paired t-tests will be utilized for select variables.  
When available, baseline from the VBP15-002 will be utilized when calculating change from baseline. 

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Efficacy Analyses: 
The primary efficacy outcome is TTSTAND (velocity).  Secondary efficacy outcomes are the NSAA 
assessment, TTCLIMB, TTRW, QMT, and the 6MWT.  TTSTAND, TTCLIMB, and TTRW will be 
analyzed using raw scores and velocity.   
The primary outcome is TTSTAND (velocity) change from VBP15-002 study baseline to Month 24 and 
will be compared between vamorolone and historical untreated controls using a restricted maximum 
likelihood (REML)-based mixed model for repeated measures (MMRM).  This model will include fixed 
effects for treatment, visit, baseline TTSTAND velocity (from the VBP15-002 study), age at study entry, 
and the treatment-by-visit interaction.  The initial model will compare combined vamorolone doses to 
untreated natural history controls and subsequent secondary models may compare individual and other 
combinations of dose levels to untreated natural history controls.  The secondary outcome measures will be 
compared using similar models.  Full details will be provided in the Statistical Analysis Plan (SAP).  
Pharmacodynamics Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover will be assessed, as 
well as exploratory biomarkers of safety and efficacy.  Biomarkers will be summarized descriptively over 
time. 
Safety Analyses: 
All subjects who received at least one dose of vamorolone (Safety Population) will be included in the safety 
analyses.  In general, descriptive statistics for each safety endpoint will be presented by the combined 
vamorolone dose level, individual dose levels, and other combinations of dose levels. 
Safety data will include BMI (raw units and z-score), height (raw units and z-score), vital signs, clinical 
laboratory test results, hand x-ray, spine x-ray, and ECG results.   
Changes in BMI z-score and height z-score will be analyzed using the same type of statistical models used 
for efficacy with vamorolone being compared with the daily prednisone and the daily deflazacort arms 
from the FOR DMD study.  Hand x-ray and spine x-ray results will also be compared with the daily 
prednisone and the daily deflazacort arms from the FOR DMD study.   
Adverse events will be summarized overall and by dose level by system organ class (SOC) and preferred 
term (using the Medical Dictionary for Regulatory Activities [MedDRA]); by relationship to study 
medication; and by intensity (CTCAE grade).   
Section Changed: 
List of Abbreviations 
Original Text: 
DMD 
Duchenne muscular dystrophy 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
Revised Text: 
DMD 
Duchenne muscular dystrophy 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 

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Original Text: 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practice 
Revised Text: 
GGT 
gamma glutamyl transferase 
GLDH 
glutamate dehydrogenase 
GLP 
Good Laboratory Practice 
Section Changed: 
1.3.2 Phase II Study in 4 to 7 years Duchenne Muscular Dystrophy Boys 
Original Text: 
1.3.2 Phase II Study in 4 to 7 years Duchenne Muscular Dystrophy Boys 
Revised Text: 
1.3.2 Pharmacokinetics in Phase II Study in 4 to 7 years Duchenne Muscular 
Dystrophy Boys (VBP15-002) 
Section Changed: 
1.3 Clinical Experience 
[Text inserted following Section 1.3.2] 
Original Text: 
[none] 
Revised Text: 
1.3.3 Safety in Phase II Studies in 4 to7 years Duchenne Muscular Dystrophy Boys 
(VBP15-002 and VBP15-003)  
Adverse events: There were no serious adverse events (SAEs) reported over the 14-day 
treatment in the Phase I clinical trial in healthy adult volunteers, nor in the four cohorts 
(0.25 mg/kg, 0.75 mg/kg, 2.0 mg/kg, and 6.0 mg/kg) of the Phase IIa study (VBP15-002; 
14-day treatment) in boys ages 4 to <7 years with DMD.  There has been a total of 
4 SAEs in the Phase IIa VBP15-003 study and one SAE to date in the VBP15-LTE 
extension study: two SAEs of pneumonia in two different subjects (both subjects 

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receiving vamorolone 0.75 mg/kg/day), one SAE of bilateral testicular torsion and one 
SAE of hypoxia in the same subject receiving 6.0 mg/kg/day, and one SAE of influenza 
associated dehydration in a subject receiving 6.0 mg/kg/day.  Each of these SAEs was 
considered unrelated to study drug, and none of them resulted in discontinuation from the 
study.  In the VBP15-003 study, there were a total of 218 TEAEs among 42 of the 48 
subjects (87.5%).  In VBP15-003 study, the TEAEs with the highest incidence were viral 
upper respiratory tract infection (41.7%); pyrexia (35.4%); cough (18.8%); vomiting 
(14.6%); and diarrhea (10.4%).   
Body Mass Index (BMI): Body Mass Index was measured throughout the VBP15-003 
study.  The mean change from baseline to Week 24 for BMI was 0.03, 0.20, 0.23, and 
1.15 for the 0.25, 0.75, 2.0, and 6.0 mg/kg/day dose level groups, respectively.  Body 
Mass Index increases generally reflect an increase in weight.  Body Mass Index z-score 
was monitored in the VBP15-003 study.  The mean change from baseline to Week 24 for 
BMI z-score for the 6.0 mg/kg/day group showed a statistically significant increase 
compared to the mean change from baseline to Week 24 for the 0.25 mg/kg/day and 
0.75 mg/kg/day dose level groups.  In contrast, the mean change from baseline to 
Week 24 for the 2.0 mg/kg/day dose level group in BMI z-score was minimal and 
comparisons with the other vamorolone dose level groups lacked statistical significance.  
The mean increase from baseline to Week 24 for BMI z-score was similar for the 6.0 
mg/kg/day group and a daily prednisone-treated historical control group.   
Potential liver toxicity: In the Phase I clinical trial in adult volunteers, vamorolone 
showed mild elevations of liver enzymes in one subject receiving 20.0 mg/kg in the 
fasted state, and dosing was halted.  All DMD subjects have elevated serum ALT and 
AST enzymes because of the muscle condition.  For that reason, two enzymes, glutamate 
dehydrogenase (GLDH) and gamma glutamyl transferase (GTT), that are preferentially 
expressed in liver were evaluated in the VBP15-003 study.  None of the mean changes in 
GLDH from baseline to any of the VBP15-003 on-treatment assessment time points were 
statistically significant for any dose level group.  Although the mean changes from 
baseline to Week 8, Week 16, and Week 24 in GLDH levels did not show a dose 
response, shift analysis of GLDH levels did suggest a possible dose-related shift to higher 

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GLDH levels at 2.0 mg/kg/day and 6.0 mg/kg/day at Weeks 16 and 24.  Mean GGT 
levels and individual subject values at each VBP15-003 assessment time point across the 
four dose level groups remained at or below the normal range. On the basis of these mean 
GLDH and GGT data, vamorolone at dose levels up to 6.0 mg/kg/day does not appear to 
induce liver toxicity over a 24-week treatment period. 
Adrenal suppression: In the VBP15-003 study, after 24 weeks of treatment, 0 of 8 tested 
participants (0.25 mg/kg/day), 1 of 12 (8.3%) tested participants (0.75 mg/kg/day), 5 of 
12 (41.7%) tested participants (2.0 mg/kg/day), and 8 of 9 (88.9%) tested participants 
(6.0 mg/kg/day) had a depressed morning cortisol (<3.6 μg/dL [100 nM]) consistent with 
chronic adrenal suppression.29 
Insulin resistance: In the VBP15-003 study, mean changes from baseline for fasting 
insulin showed dose-and time-related changes for all dose level groups at Week 12 and 
Week 24.  Statistical significance was observed for mean increase from baseline for the 
6.0 mg/kg/day dose level group at Week 12 and Week 24.  
Bone Turnover: In the VBP15-003 study, pharmacodynamic biomarker testing for bone 
turnover markers suggested that vamorolone does not have the detrimental bone effects 
observed with prednisone and deflazacort. 
Section Changed: 
1.4 Rationale for Study Design 
Paragraphs 4, 5, and 8 
Original Text: 

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The vamorolone development program has made advances in biomarker discovery and 
development in DMD, with a subset of these studies recently published.42  A panel of 
biomarkers in DMD patient sera that show response to chronic (~4 month) treatment with 
glucocorticoids has been identified.  These chronic prednisone PD biomarkers were 
discovered through study of serum samples of DMD patients enrolled in the Cooperative 
International Neuromuscular Research Group (CINRG) Duchenne Natural History Study 
(DNHS).  
Revised Text: 
The vamorolone development program has made advances in biomarker discovery and 
development in DMD, with a subset of these studies recently published.42  A panel of 
biomarkers in DMD patient sera that show response to chronic (~4 month) treatment with 
glucocorticoids has been identified.  These chronic prednisone PD biomarkers were 
discovered through study of serum samples of DMD patients enrolled in the Cooperative 
International Neuromuscular Research Group (CINRG) Duchenne Natural History Study 
(DNHS), and data have been reported for the VBP15-002 study.43   
Original Text: 
Adrenal axis suppression is a well-documented safety signal with chronic use of 
glucocorticoids.  As noted above, nonclinical data suggest that vamorolone may not cause 
adrenal axis suppression.  To test whether vamorolone treatment causes chronic adrenal 
axis suppression, four steroid hormones will be tested by LC-MS in the vamorolone-
treated DMD boys (17-hydroxyprogesterone, cortiscosterone, testosterone, 
11-deoxycortisol) (Table 7).  All four steroid hormones showed significant reductions 
after glucocorticoid treatment in DMD boys in the cross-sectional and longitudinal 
CINRG DNHS participants. 
Revised Text: 
Adrenal axis suppression is a well-documented safety signal with chronic use of 
glucocorticoids.  As noted in Section 1.3.3, in the VBP15-003 study, after 24 weeks of 
treatment, 0 of 8 tested participants (0.25 mg/kg/day), 1 of 12 (8.3%) tested participants 
(0.75 mg/kg/day), 5 of 12 (41.7%) tested participants (2.0 mg/kg/day), and 8 of 9 (88.9%) 

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tested participants (6.0 mg/kg/day) had a depressed morning cortisol (<3.6 μg/dL 
[100 nM]) consistent with chronic adrenal suppression.  To further evaluate the effects of 
vamorolone on chronic adrenal axis suppression, four steroid hormones (17-
hydroxyprogesterone, corticosterone, testosterone, 11-deoxycortisol) are being analyzed 
by LC-MS in the VBP15-LTE study (Table 7).  All four steroid hormones showed 
significant reductions after glucocorticoid treatment in DMD boys in the cross-sectional 
and longitudinal CINRG DNHS participants. 
Original Text: 
Comparisons of efficacy and safety parameters with historical natural history 
(untreated)43,44,45,46 and prednisone-treated control groups47 will be performed as primary 
outcomes of this VBP15-LTE study. 
Revised Text: 
Comparisons of efficacy and safety parameters with historical natural history 
(untreated)44, 45, 46, 47 and prednisone- and deflazacort-treated control groups48 will be 
performed as outcomes of this VBP15-LTE study. 
Section Changed: 
1.5 Overall Benefit/Risk 
Original Text: 
The current study is a long-term safety and efficacy study in young boys with DMD.  It is 
anticipated that the adverse effect profile of the investigational product will be more 
favorable than standard of care glucocorticoids in the long term.  The adverse effects of 
vamorolone over long term treatment are not currently known.  In the Phase I SAD/MAD 
study in healthy adults, no serious adverse events were observed in any cohort through 
2 weeks of treatment.  Cohorts tested in the Phase I MAD study were 1.0, 3.0, 9.0 and 
20.0 mg/kg/day for 14 days.  In the Phase I MAD clinical trial in adult volunteers, 
vamorolone showed suppression of the adrenal axis at higher doses (9.0 mg/kg/day and 
20.0 mg/kg/day in the fasted state).29  Instructions for detecting adrenal crisis and the 
circumstances in which stress dose steroids should be provided will be included in the 
informed consent form (ICF).  One human subject in the Phase I studies in the 20.0 

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mg/kg/day MAD dose group showed mild elevations of liver enzymes, and dosing was 
halted.  Investigators should monitor clinical study participants closely to identify 
elevations in liver-specific enzymes. 
Subjects may or may not receive direct health benefit from participating in the study.  
Subjects will receive vamorolone at one of four planned dose levels (0.25 mg/kg/day, 
0.75 mg/kg/day, 2.0 mg/kg/day, or 6.0 mg/kg/day) over the course of the 24-week 
VBP15-003 trial, and then continue on this dose in the current VBP15-LTE study for up 
to 2 years.  As noted above, the Medical Monitor, Study Director, and Site Investigator 
may opt to dose escalate to a higher dose level during the VBP15-LTE once the subject 
has been on the initial dose in VBP15-LTE for at least 1 month, the next higher dose is 
determined to be safe in the VBP15-002 Phase IIa Study, and no safety issues with that 
dose have emerged in the VBP15-003 Phase IIa extension study.  While it is anticipated 
from nonclinical studies that these dose levels may be efficacious in the treatment of 
DMD, there are no clinical efficacy data yet available to validate this hypothesis.  In view 
of the initial clinical evidence of safety and the monitorable nature of key nonclinical 
toxicological findings, data support an acceptable risk profile for vamorolone. 
Revised Text: 
The current study is a long-term safety and efficacy study in young boys with DMD.  It is 
anticipated that the adverse effect profile of the investigational product will be more 
favorable than standard of care glucocorticoids in the long term (see Section 1.3.3).  The 
adverse effects of vamorolone over long term treatment are not currently known.   
Instructions for detecting adrenal crisis and the circumstances in which stress dose 
steroids should be provided are included in the informed consent form (ICF), and 
Investigators should monitor clinical study participants closely to identify elevations in 
liver-specific enzymes. 
Potential health benefits: Subjects may or may not receive direct health benefit from 
participating in the study.  Subjects will receive vamorolone at one of four planned dose 
levels (0.25 mg/kg/day, 0.75 mg/kg/day, 2.0 mg/kg/day, or 6.0 mg/kg/day) over the 
course of the 24-week VBP15-003 trial, and then continue on this dose in the current 

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VBP15-LTE study for up to 2 years.  As noted above, the Medical Monitor, Study 
Director, and Site Investigator may opt to dose escalate to a higher dose level during the 
VBP15-LTE once the subject has been on the initial dose in VBP15-LTE for at least one 
month, the next higher dose is determined to be safe in the VBP15-002 Phase IIa Study, 
and no safety issues with that dose have emerged in the VBP15-003 Phase IIa extension 
study.  In the VBP15-003 study, clinical efficacy was assessed by Timed Function Tests.  
Improvement in Time to Stand, Time to Climb, Time to Run/Walk 10 Meters, and 
6-Minute Walk Test were seen predominantly for the 2.0 and 6.0 mg/kg/day dose level 
groups, with many of the improvements showing statistical significance compared to an 
untreated Duchenne Natural History Group.  In view of the initial clinical evidence of 
safety, the improvements seen in assessments of efficacy, and the monitorable nature of 
key potential adverse effects, data support an acceptable benefit/risk profile for 
vamorolone. 
Sections Changed: 
Synopsis: Objectives 
2.1 Study Objectives  
Original Text: 
2.1.1 Primary Objectives 
The primary objectives of this study are: 
1. To evaluate the long-term safety and tolerability of vamorolone, administered 
orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period, in 
young boys with DMD who completed protocol VBP15-003;  
2. To compare the efficacy, as measured by the Time to Stand Test (TTSTAND), of 
vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month 
Treatment Period vs. untreated DMD historical controls in young boys with 
DMD; and 
3. To compare the safety, as measured by body mass index (BMI) z-score, of 
vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month 

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Treatment Period vs. prednisone-treated historical controls in young boys with 
DMD. 
2.1.2 Secondary Objectives 
The secondary objectives of this study are: 
1. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period vs. prednisone-treated historical 
controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin 
resistance, adrenal axis suppression, and bone turnover); and 
2. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period, on muscle strength, mobility and 
functional exercise capacity vs. untreated DMD historical controls as measured by 
Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment (NSAA), 
Time to Climb Test (TTCLIMB), 6-minute Walk Test (6MWT), and Quantitative 
Muscle Testing (QMT) in young boys ages with DMD. 
2.1.3 Exploratory Objectives 
The exploratory objectives of this study are: 
1. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on Quality of Life measures 
(Pediatric Outcomes Data Collection Instrument [PODCI]); and 
2. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on an extended panel of exploratory 
PD biomarkers using somaSCAN aptamer arrays, steroid hormone profiling, and 
other biomarker methods. 
Revised Text: 
2.1.1 Primary Objectives 
The primary objectives of this study are: 
1. To evaluate the long-term safety and tolerability of vamorolone, administered 
orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period, in young 
boys with DMD who completed protocol VBP15-003; and 

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2. To compare the efficacy, as measured by the Time to Stand Test (TTSTAND), of 
vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month 
Treatment Period vs. untreated DMD historical controls in young boys with 
DMD. 
2.1.2 Secondary Objectives 
The secondary objectives of this study are: 
1. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on serum pharmacodynamic (PD) 
biomarkers of safety (insulin resistance, adrenal axis suppression, and bone 
turnover);  
2. To investigate the effects of vamorolone, administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period, on muscle strength, mobility and 
functional exercise capacity vs. untreated DMD historical controls as measured by 
Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment (NSAA), 
Time to Climb Test (TTCLIMB), 6-minute Walk Test (6MWT), and Quantitative 
Muscle Testing (QMT) in young boys with DMD; and 
3. To compare the safety, as assessed by bone age, spine fractures, BMI z-score, and 
height z-score, of vamorolone, administered orally at daily doses up to 6.0 mg/kg 
over a 24-month Treatment Period vs. prednisone- and deflazacort-treated 
historical control boys with DMD. 
2.1.3 
Exploratory Objectives 
The exploratory objectives of this study are: 
1. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on Quality of Life measures 
(Pediatric Outcomes Data Collection Instrument [PODCI]); 
2. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on additional exploratory PD 
biomarkers; and 

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3. To determine if established genetic modifiers of DMD (gene polymorphisms 
associated with disease severity, or response to glucocorticoid treatment) are 
similarly associated with vamorolone-treated DMD patients (baseline disease 
severity, or response to vamorolone treatment). 
Section Changed: 
2.2 Study Endpoints, Safety Endpoints 
Original Text: 
2.2.1 Safety Endpoints 
2.2.1.1 Primary Safety Endpoint 
1. BMI z-score: Comparison with a prednisone-treated historical control group for 
change from Baseline to Month 12. 
2.2.1.2 Additional Safety Endpoints 
1. BMI z-score: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points;  
2. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 
by system organ class (SOC): Overall by treatment, by treatment and relationship, 
and by treatment and intensity (see 7.2.6); 
3. Vital signs [blood pressure, heart rate, respiratory rate, oral body temperature]: 
Change from Baseline to each of the scheduled on-treatment and post-treatment 
assessment time points; 
4. Body weight: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points; 
5. Clinical laboratory values (hematology and biochemistry): Change from Baseline 
to each of the scheduled on-treatment and post-treatment assessment time points; 
6. Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high 
density lipoprotein [HDL]):  Change from Baseline to each of the scheduled on-
treatment and post-treatment assessment time points; 

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7. Urinalysis by dipstick and microscopic analysis: Change from Baseline to each of 
the scheduled on-treatment and post-treatment assessment time points; 
8. 12-lead electrocardiogram (ECG): Change from Baseline to each of the scheduled 
on-treatment and post-treatment assessment time points; 
Data for the following additional safety outcomes will be listed only: 
1. Physical examination findings at Pretreatment, Month 12, and Month 24. 
Revised Text: 
2.2.1 Safety Endpoints 
1. BMI z-score: Comparison with prednisone- and deflazacort-treated historical 
control groups for change from Baseline to Month 12 and Month 24; 
2. BMI z-score: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points;  
3. Height z-score: Comparison with prednisone- and deflazacort-treated historical 
control groups for change from Baseline to Month 12 and Month 24; 
4. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 
by system organ class (SOC): Overall by treatment, by treatment and relationship, 
and by treatment and intensity (see Section 7.2.6); 
5. Vital signs [blood pressure, heart rate, respiratory rate, oral body temperature]: 
Change from Baseline to each of the scheduled on-treatment and post-treatment 
assessment time points; 
6. Body weight: Change from Baseline to each of the scheduled on-treatment and 
post-treatment assessment time points; 
7. Clinical laboratory values (hematology and biochemistry): Change from Baseline 
to each of the scheduled on-treatment and post-treatment assessment time points; 
8. Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high 
density lipoprotein [HDL]):  Change from Baseline to each of the scheduled on-
treatment and post-treatment assessment time points; 

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9. Urinalysis by dipstick and microscopic analysis: Change from Baseline to each of 
the scheduled on-treatment and post-treatment assessment time points; 
10. 12-lead electrocardiogram (ECG): Change from Baseline to each of the scheduled 
on-treatment and post-treatment assessment time points; 
11. Hand x-ray: bone age at Month 24; 
12. Spine x-ray: Spine fractures at Month 24. 
Data for the following additional safety outcomes will be listed only: 
1. Physical examination findings at Pretreatment, Month 12, and Month 24. 
Section Changed: 
2.2.2 Clinical Efficacy Endpoints 
Original Text: 
2.2.2.1 
Primary Clinical Efficacy Endpoint 
1. Time to Stand Test (TTSTAND) velocity (rise/second):  Comparison with a 
historical natural history (untreated) control group for change from Baseline to 
Month 12. 
2.2.2.2 
Secondary Efficacy Endpoints 
1. Time to Stand Test (TTSTAND) velocity (rise/second):  Change from Baseline to 
each of the scheduled on-treatment and post-treatment assessment time points; 
Revised Text: 
2.2.2.1 
Primary Clinical Efficacy Endpoint 
1. Time to Stand Test (TTSTAND) velocity (rise/second):  Comparison with a 
historical natural history (untreated) control group for change from Baseline to 
Month 24. 
2.2.2.2 
Secondary Efficacy Endpoints 

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1. Time to Stand Test (TTSTAND) velocity (rise/second):  Comparison with a 
historical natural history (untreated) control group for change from Baseline to 
Month 12; 
2. Time to Stand Test (TTSTAND):  Change from Baseline to each of the scheduled 
on-treatment and post-treatment assessment time points; 
Section Changed: 
2.2.2.3 Exploratory Efficacy Endpoint 
Original Text: 
2.2.2.3  
Exploratory Efficacy Endpoint 
1. To investigate the effects of vamorolone administered orally at daily doses up to 
6.0 mg/kg over a 24-month Treatment Period on Quality of Life measures (PODCI). 
Revised Text: 
[text deleted] 
Section Changed: 
2.2.3 Pharmacodynamic Endpoints 
Original Text: 
Concentrations of serum and/or salivary PD biomarkers of adrenal suppression (morning 
salivary cortisol), insulin resistance (fasting insulin and glucose), and bone turnover 
(osteocalcin, serum carboxy-terminal telopeptide of type I collagen [CTX1]). 
Revised Text: 
Concentrations of serum PD biomarkers of adrenal suppression, insulin resistance, and 
bone turnover. 
Section Changed: 
2.2.4 Exploratory Endpoints 
Original Text: 
2.2.4 Exploratory Endpoints 

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1. Levels of an extended panel of PD efficacy and safety biomarkers using 
somaSCAN aptamer arrays, steroid hormone profiling, and other biomarker 
methods. 
Revised Text: 
2.2.4 Exploratory Endpoints 
1. Pediatric Outcomes Data Collection Instrument (PODCI): Change from baseline 
to each of the scheduled on-treatment and post-treatment assessment time points; 
2. Levels of additional exploratory PD biomarkers; and 
3. DNA testing for established genetic modifiers of DMD. 
Section Changed: 
3.1 Overall Study Design 
Paragraphs 5 and 7 
Original Text: 
Subjects in the VBP-LTE will begin dosing at the same vamorolone dose level they 
received at the time they completed the Week 24 Final Visit in the VBP15-003 Phase IIa 
extension core study.  Subjects, once they have been on their initial dose in the 
VBP15-LTE study for at least one month, may have their dose escalated at the discretion 
of the Study Chair and Medical Monitor once that dose has been determined to be safe in 
the VBP15-002 Phase IIa Study, and no safety issues have emerged at that dose in the 
VBP15-003 Phase IIa extension study.  Subjects will continue to receive vamorolone at 
one of the assigned dose levels for the duration of the 24-month Treatment Period, unless 
ongoing safety data indicate the dose level should be de-escalated. 
Revised Text: 
Subjects in the VBP-LTE will begin dosing at the same vamorolone dose level they 
received at the time they completed the Week 24 Final Visit in the VBP15-003 Phase IIa 
extension core study.  Subjects, once they have been on their initial dose in the 
VBP15-LTE study for at least one month, may have their dose escalated at the discretion 
of the Study Chair and Medical Monitor once that dose has been determined to be safe in 
the VBP15-002 Phase IIa Study, and no safety issues have emerged at that dose in the 

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VBP15-003 Phase IIa extension study.  Subjects may continue to have their dose of study 
medication escalated incrementally at no shorter than one-month intervals to the 
maximum dose tested and assessed as safe in the VBP15-002 and VBP15-003 studies, 
6.0 mg/kg/day.  Subjects will continue to receive vamorolone at one of the assigned dose 
levels for the duration of the 24-month Treatment Period, unless ongoing safety data 
indicate the dose level should be de-escalated. 
Original Text: 
In the event any clinical observation suggests an intolerability for an individual subject to 
the study medication, in the opinion of the Investigator, the subject’s dose level may be 
decreased to the next lower dose level (e.g., a subject taking 6.0 mg/kg/day decreased to 
2.0 mg/kg/day) and maintained at that lower dose level throughout the duration of the 
Treatment Period.  In the event the next lower dose level is also not tolerated and is 
considered a safety risk to the subject, in the opinion of the Investigator, Study Chair, and 
Medical Monitor, the subject should be withdrawn from the study.  Details of dose 
interruption, de-escalation, and discontinuation are presented in 5.6. 
Revised Text: 
In the event any clinical observation suggests an intolerability for an individual subject to 
the study medication, in the opinion of the Investigator, the subject’s dose level may be 
decreased to the next lower dose level and maintained at that lower dose level throughout 
the duration of the Treatment Period, with the caveat stated below for subjects 
de-escalating from 6.0 mg/kg/day to 2.0 mg/kg/day.  In the event the next lower dose 
level is also not tolerated and is considered a safety risk to the subject, in the opinion of 
the Investigator, Study Chair, and Medical Monitor, the subject should be withdrawn 
from the study.  Subjects whose dose is decreased from 6.0 mg/kg/day to 2.0 mg/kg/day 
may have their dose subsequently increased to 4.0 mg/kg/day if they have been taking the 
2.0 mg/kg/day dose for at least one month and, in the opinion of the Investigator, 
balancing efficacy with safety concerns, they could benefit from an intermediate higher 
dose.  Details of dose interruption, de-escalation, and discontinuation are presented in 
Section 5.6. 

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Section Changed: 
5.4 Rationale for Dose Selection 
Paragraph 3 
Original Text: 
Based on the Phase I PD biomarker safety data presented in 1.3, safety signals reflective 
of insulin resistance, bone turnover, immune suppression, or adrenal suppression are not 
anticipated at any of the planned long-term extension dose levels. 
Revised Text: 
Based on the safety data presented in Section 1.3.3, the doses initially selected for this 
study are appropriate for evaluation in a long-term extension study. 
Section Changed: 
5.6 Study Drug Dose Interruption, De-escalation, or Discontinuation 
Paragraph 1 
Original Text: 
Administration of study drug to individual subjects should be interrupted, and the case 
discussed with the Study Chair and Medical Monitor within 24 hours, in the event any 
clinical observation suggests an intolerability of an individual subject to the study 
medication, in the opinion of the Investigator.  In such an event, the subject’s dose level 
may be decreased to the next lower dose level (e.g., a subject taking 6.0 mg/kg/day 
decreased to 2.0 mg/kg/day) and maintained at that lower dose level throughout the 
duration of the study.  In the event the next lower dose level is also not tolerated and is 
considered a safety risk to the subject, in the opinion of the Investigator, Study Chair and 
Medical Monitor, the subject should be withdrawn from the study. 
Revised Text: 
Administration of study drug to individual subjects should be interrupted, and the case 
discussed with the Study Chair and Medical Monitor within 24 hours, in the event any 
clinical observation suggests an intolerability to the study medication and a safety risk to 
an individual subject, in the opinion of the Investigator.  In such an event, or in situations 
where the intolerability is not considered an immediate safety risk to the subject, the 
subject’s dose level may be decreased to the next lower dose level and maintained at that 

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lower dose level throughout the duration of the study, with the caveat stated below for 
subjects de-escalating from 6.0 mg/kg/day to 2.0 mg/kg/day.  In the event the next lower 
dose level is also not tolerated and is considered a safety risk to the subject, in the opinion 
of the Investigator, Study Chair and Medical Monitor, the subject should be withdrawn 
from the study. 
Subjects whose dose is decreased from 6.0 mg/kg/day to 2.0 kg/kg/day may have their 
dose subsequently increased to 4.0 mg/kg/day if they have been taking the 2.0 mg/kg/day 
dose for at least one month and, in the opinion of the Investigator, balancing efficacy 
with safety concerns, they could benefit from an intermediate higher dose.  
Section Changed: 
5.7.3 Prohibited Therapies 
Paragraph 1, Bullet #5 
Original Text: 
• Live attenuated vaccines (use must be avoided for the duration of participation in 
the study); 
• Any investigational medications other than vamorolone (use must be discontinued 
at least 3 months prior to the first dose of study medication). 
Revised Text: 
• Live attenuated vaccines (use must be avoided for the duration of participation in 
the study); 
• Medications indicated for the treatment of DMD, including Exondys 51 and 
Translarna (use must be avoided for the duration of participation in the study); 
• Any investigational medications other than vamorolone (use must be discontinued 
at least 3 months prior to the first dose of study medication). 
Section Changed: 
6.1 Time and Events Schedule 
Table 8 

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Original Text: 
Table 8 
Schedule of Study Activities 
Pretreatment Period 
Treatment Period 
Dose-
tapering 
Period 
Baseline 
 
Day 
Month 
Study Day or Week/Visit 
-1a 
1b 
1 
(±7d) 
3 
(±7d) 
6 
(±7d) 
9 
(±7d) 
12 
(±7d) 
15 
(±7d) 
18 
(±7d) 
21 
(±7d) 
24c 
(±7d) 
24-25d 
(±7d) 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
Xe 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
X 
 
 
 
 
 
 
 
 
 
 
 
Interim Medical History 
Xf 
 
 
 
 
 
 
 
 
 
 
 
Medication History 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Weight 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsi 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Clinical Labsj 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Urinalysisk 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
 
Blood for Serum PD Biomarker Panell 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Fasting morning blood for insulin, 
glucose, cortisolm 
 
 
 
 
 
X 
 
 
 
X 
 
 
12-lead ECGn 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Dispense Study Medication 
X 
 
 
X 
X 
Xo 
X 
X 
X 
Xo 
X 
 
Return Study Medication/ Compliance 
Monitoring 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Medication Dosing 
 
X 
 
 
 
 
 
 
 
 
X 
 
Vamorolone dose taperingp,q 
 
 
 
 
 
 
 
 
 
 
 
X 
Time to Stand Test (TTSTAND) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Climb Test (TTCLIMB) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Run/Walk Test (TTRW) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
NSAAr 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Quantitative Muscle Testing (QMT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Six-minute Walk Test (6MWT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Pediatric Outcomes (PODCI) Data 
Collection Instrument 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Dispense Subject Diariess 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Return Subject Diaries  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE Recordingt 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Concomitant Medications 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Discharge from Study 
 
 
 
 
 
 
 
 
 
 
Xu 
Xv 

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Revised Text: 
Table 8 
Schedule of Study Activities 
Pretreatment Period 
Treatment Period 
Dose-
tapering 
Period 
Baseline 
 
Day 
Month 
Study Day or Month/Visit 
-1a 
1b 
1 
(±7d) 
3 
(±7d) 
6 
(±7d) 
9 
(±7d) 
12 
(±7d) 
15 
(±7d) 
18 
(±7d) 
21 
(±7d) 
24c 
(±7d) 
24-25d 
(±7d) 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
Xe 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
X 
 
 
 
 
 
 
 
 
 
 
 
Interim Medical History 
Xf 
 
 
 
 
 
 
 
 
 
 
 
Medication History 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Weight 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsi 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Clinical Labsj 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Urinalysisk 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
 
Blood for Serum PD Biomarker Panell 
Xh 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Fasting morning blood for insulin, 
glucose, cortisolm 
 
 
 
 
 
X 
 
 
 
X 
 
 
Blood for DNA Testing 
 
 
 
 
 
 
 
 
 
 
X 
 
12-lead ECGn 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Dispense Study Medication 
X 
 
 
X 
X 
Xo 
X 
X 
X 
Xo 
X 
 
Return Study Medication/ Compliance 
Monitoring 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Medication Dosing 
 
X 
 
 
 
 
 
 
 
 
X 
 
Vamorolone dose taperingp,q 
 
 
 
 
 
 
 
 
 
 
 
X 
Time to Stand Test (TTSTAND) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Climb Test (TTCLIMB) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Time to Run/Walk Test (TTRW) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
NSAAr 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Quantitative Muscle Testing (QMT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Six-minute Walk Test (6MWT) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Pediatric Outcomes Data Collection 
Instrument (PODCI) 
Xh 
 
 
 
 
 
X 
 
 
 
X 
 
Spine x-ray 
 
 
 
 
 
 
 
 
 
 
X 
 
Hand x-ray 
 
 
 
 
 
 
 
 
 
 
X 
 
Dispense Subject Diariess 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Return Subject Diaries  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE Recordingt 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Concomitant Medications 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Discharge from Study 
 
 
 
 
 
 
 
 
 
 
Xu 
Xv 

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Table 8, Footnote l 
Original Text: 
l. 
Blood collected for pharmacodynamic safety biomarkers (osteocalcin, CTX1), and exploratory safety and 
efficacy biomarkers (somaSCAN, steroid hormones, others). 
Revised Text: 
l. 
Blood collected for pharmacodynamic safety biomarkers and exploratory safety and efficacy biomarkers.  
Section Changed: 
6.3.1 Baseline Period (Day -1) 
Paragraph 6, Bullet #11 
Original Text: 
• 
Blood samples for PD biomarkers including osteocalcin, and CTX1.  Blood will 
also be collected and stored for exploratory somaSCAN aptamer panel, steroid 
hormone profiling, and other studies.  (Not to be repeated if Baseline Day -1 is 
≤ 28 days after the VBP15-003 Week 24 Final Visit assessment date.)  (see 7.3.7) 
Revised Text: 
• 
Blood samples for PD biomarkers.  Blood will also be collected and stored for 
exploratory PD biomarkers.  (Not to be repeated if Baseline Day -1 is ≤ 28 days 
after the VBP15-003 Week 24 Final Visit assessment date.)  (see 7.3.7) 
Section Changed: 
6.3.3 Treatment Period Months 1-24 
Paragraph 4 
Original Text: 
Clinical efficacy assessments (TTSTAND, TTRW, TTCLIMB, NSAA, 6MWT, and 
QMT) and the Pediatric Outcomes Data Collection Instrument (PODCI) will be 
conducted at 12 and 24 months.  Weight will be recorded every visit from 3-24 months 
and height will be measured at 12 and 24 months.  Vital signs will be recorded at each 
study visit.  A physical examination will be performed at Months 12 and 24.  A 12-lead 
ECG will be recorded at Months 12 and 24.  Blood and urine samples for clinical 
laboratory tests, and blood for the serum PD biomarker panel including somaSCAN, 

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steroid hormone profiling, and others will be collected at 6, 12, 18, and 24 months (see 
Table 8).  Adverse events, including SAEs, and concomitant medications will be 
assessed at each study visit and recorded throughout the study. 
Revised Text: 
Clinical efficacy assessments (TTSTAND, TTRW, TTCLIMB, NSAA, 6MWT, and 
QMT) and the Pediatric Outcomes Data Collection Instrument (PODCI) will be 
conducted at 12 and 24 months.  Weight will be recorded every visit from 3-24 months 
and height will be measured at 12 and 24 months.  Vital signs will be recorded at each 
study visit.  A physical examination will be performed at Months 12 and 24.  A 12-lead 
ECG will be recorded at Months 12 and 24.  Blood and urine samples for clinical 
laboratory tests, and blood for PD biomarkers will be collected at 6, 12, 18, and 24 
months (see Table 8).  Blood will be collected at Month 24 for DNA testing for 
established genetic modifiers of DMD.  Spine x-ray and hand x-ray will be performed at 
Month 24.  Adverse events, including SAEs, and concomitant medications will be 
assessed at each study visit and recorded throughout the study. 
Section Changed: 
6.3.4 Dose-Tapering Period Months 24-25 
Paragraphs 2 and 3 
Original Text: 
The subject’s weight recorded at the Month 24 Visit will be used to calculate dose and 
dose volume for all dose de-escalations during the Dose-tapering Period (see 
Appendix 14.1). 
Table 9 
Vamorolone Dose Tapering 
Treatment Period 
Vamorolone Dose 
Level at Month 24 
Final Visit 
Dose Level for 
First Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Second Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Third Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fourth Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fifth Week 
Following the 
Month 24 
Final Visit 
0.25 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
 
0.75 mg/kg/day 
0.375 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
2.0 mg/kg/day 
1 mg/kg/day 
0.5 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
 
6.0 mg/kg/day 
3 mg/kg/day 
1.5 mg/kg/day 
0.75 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 

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All subjects participating in the Dose-tapering Period will return to the study site for final 
study assessments approximately one week after the final dose de-escalation (i.e., 
approximately one week after the subject has received his last dose of vamorolone).  The 
duration of the Dose-tapering Period will therefore vary depending upon the vamorolone 
dose received by the subject at completion of the Month 24 Visit of the Treatment Period, 
from a total duration of two weeks (for subjects receiving 0.25 mg/kg/day vamorolone; 
final study visit two weeks following the Month 24 Final Visit) to five weeks (for 
subjects receiving vamorolone 6.0 mg/kg/day; final study visit five weeks following the 
Month 24 Final Visit). 
Revised Text: 
The subject’s weight recorded at the Month 24 Visit will be used to calculate dose and 
dose volume for all dose de-escalations during the Dose-tapering Period (see 
Appendix 14.1). 
Table 9 
Vamorolone Dose Tapering 
Treatment Period 
Vamorolone Dose 
Level at Month 24 
Final Visit 
Dose Level for 
First Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Second Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Third Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fourth Week 
Following the 
Month 24 
Final Visit 
Dose Level for 
Fifth Week 
Following the 
Month 24 
Final Visit 
0.25 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
 
0.75 mg/kg/day 
0.375 mg/kg/day 
0.125 mg/kg/day 
0 mg/kg/day 
 
 
2.0 mg/kg/day 
1 mg/kg/day 
0.5 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
 
4.0 mg/kg/day 
2 mg/kg/day 
1 mg/kg/day 
0.5 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
6.0 mg/kg/day 
3 mg/kg/day 
1.5 mg/kg/day 
0.75 mg/kg/day 
0.25 mg/kg/day 
0 mg/kg/day 
 
All subjects participating in the Dose-tapering Period will return to the study site for final 
study assessments approximately one week after the final dose de-escalation (i.e., 
approximately one week after the subject has received his last dose of vamorolone).  The 
duration of the Dose-tapering Period will therefore vary depending upon the vamorolone 
dose received by the subject at completion of the Month 24 Visit of the Treatment Period, 
from a total duration of two weeks (for subjects receiving 0.25 mg/kg/day vamorolone; 
final study visit two weeks following the Month 24 Final Visit) to five weeks (for 

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subjects receiving vamorolone 4.0 mg/kg/day or 6.0 mg/kg/day; final study visit five 
weeks following the Month 24 Final Visit). 
Section Changed: 
7.1 Demographic Assessments 
Original Text: 
Demographic information (birth date, race, and ethnicity) collected during the 
VBP15-002 study will be used for this study; collection of demographic data will not be 
repeated during this study.  
Revised Text: 
Demographic information (birth date, race, and ethnicity) collected during the 
VBP15-002 study will be used for this study; collection of demographic data will not be 
repeated during this study. 
7.1.1 Genetic Modifiers of DMD 
Approximately 8.5 mL of blood will be collected at the Month 24 Visit for DNA testing 
to determine if established genetic modifiers of DMD (gene polymorphisms associated 
with disease severity or response to glucocorticoid treatment) are similarly associated 
with vamorolone-treated DMD patients (baseline disease severity or response to 
vamorolone treatment).   
DNA testing will be performed by a certified central laboratory. 
The procedures for the collection, handling, and shipping of blood samples for DNA 
testing will be specified in the Laboratory Manual(s) provided to the clinical center.  
Results will be compared to historical control data for glucocorticoid responders and 
non-responders. 
Section Changed: 
7.2 Safety and Tolerability Assessments 
Text inserted following Section 7.2.6  
Original Text: 
[none] 

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Revised Text: 
7.2.7 
Bone Age (Hand X-ray) 
Bone age will be assessed by hand x-ray at the Month 24 Visit.  Hand radiography will be 
performed as described in the Manual of Operations.  Hand radiographs will be analyzed 
centrally by a certified radiologist through the imaging coordinating center in Ottawa, 
Canada.   
7.2.8 Spine X-ray 
Data on bone health will also be collected by lateral spine x-ray (T4-L5) at the Month 24 
Visit.  Lateral spine x-rays will be analyzed centrally by two certified pediatric 
radiologists at Children’s Hospital of Ottawa in Ottawa, Canada, who are blinded to the 
results of one another; a third radiologist will resolve any discrepancies arising from the 
first two readings.  Quantification of any vertebral fractures detected will be performed.   
Fractures will be recorded as AEs. 
Section Changed: 
7.3.1 Time to Stand Test (TTSTAND) 
Paragraph 2 
Original Text: 
The TTSTAND measures the speed (m/s; velocity) with which the child can stand to an 
erect position from supine (floor), and is administered as part of the NSAA (see 7.3.4).  
Complete instructions for administering and scoring the TTSTAND are given in the study 
manual to be supplied to the sites prior to study start. 
Revised text: 
The TTSTAND measures the speed (rise/second; velocity) with which the child can stand 
to an erect position from supine (floor), and is administered as part of the NSAA (see 
Section 7.3.4).  Complete instructions for administering and scoring the TTSTAND are 
given in the study manual to be supplied to the sites prior to study start. 
Section Changed: 
7.3.7 Pharmacodynamic Biomarker Panel 

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Paragraph 2, Table 12 
Original Text: 
The biomarker analysis includes osteocalcin and CTX1.  Blood will also be collected at 
each of these time points and stored for exploratory efficacy and safety 
pharmacodynamic biomarkers using somaSCAN aptamer panels, steroid hormone 
profiling, and others. 
Revised Text: 
Blood will also be collected at each of these time points and stored for exploratory 
efficacy and safety pharmacodynamic biomarkers. 
Original Text: 
Table 12 
Pharmacodynamic Biomarkers 
Adrenal Suppression 
Morning Cortisol 
Insulin Resistance 
Fasting Glucose 
Fasting Insulin 
Bone Turnover 
Osteocalcin 
CTX1 
Exploratory Biomarkers 
somaSCAN aptamer profiling, steroid hormone profiling, and others 
Revised Text: 

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Table 12 
Pharmacodynamic Biomarkers 
Adrenal Suppression 
Morning Cortisol 
ACTH 
17- hydroxyprogesterone 
Testosterone 
Corticosterone 
11- deoxycortisol 
Insulin Resistance 
Fasting Glucose 
Fasting Insulin 
HbA1c 
Bone Turnover 
Osteocalcin 
CTX1 
P1NP 
Exploratory Biomarkers 
Other PD biomarkers 
Section Changed: 
7.4 Total Blood Volume Required 
Original Text: 
7.4 
Total Blood Volume Required 
The number and volume of blood samples and total volume of blood to be collected from 
each subject throughout the duration of the 24-month study are summarized in Table 13.  
A total of approximately 96-137 mL of blood will be collected from each subject over the 
course of the up to 24-month study. 

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Table 13 
Blood Sample Number and Volume 
 
Total mL of Blood 
Test 
Day -1a Month 
6 
Month 
9 
Month 
12 
Month 
18 
Month 
21 
Month 
24 
End of 
Dose-
tapering 
Periodb 
Total 
Volume 
Clinical Safety Labsc 
4.5 
4.5 
 
4.5 
4.5 
 
4.5 
4.5 
18-27 
PD Biomarker Panel 
15d 
17e 
 
17e 
17e 
 
17e 
17e 
68-100 
PD Insulin/Glucose/ 
Cortisol 
 
 
5f 
 
 
5f 
 
 
10 
Total Volume by Visit 
(mL) 
19.5 
21.5 
5 
21.5 
21.5 
5 
21.5 
21.5 
96-137 
Total Volume: approximately 96-137 
 a Day -1 blood draws for clinical labs and PD biomarkers will not be repeated for subjects whose Day -1 Visit is 
≤ 28 days following VBP15-003 Week 24 Final Visit and who had blood drawn for clinical labs and PD biomarkers at 
that Visit. 
b Only subjects who participate in the Dose-tapering Period will have bloods drawn. 
c Hematology, Chemistry, Lipids. 
d cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, ACTH, 
SomaScan, and proteomics testing.  
e cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, ACTH, 
HbA1c, SomaScan, and proteomics testing.  
f Subjects must have fasted ≥ 6 hours prior to blood draws.  Blood will be drawn prior to administration of the dose of 
study medication. 
 
Revised Text: 
7.4 
Total Blood Volume Required 
The number and volume of blood samples and total volume of blood to be collected from 
each subject throughout the duration of the 24-month study are summarized in Table 13.  
A total of approximately 104.5-145.5 mL of blood will be collected from each subject 
over the course of the up to 24-month study. 

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Table 13 
Blood Sample Number and Volume 
 
Total mL of Blood 
Test 
Day -1a Month 
6 
Month 
9 
Month 
12 
Month 
18 
Month 
21 
Month 
24 
End of 
Dose-
tapering 
Periodb 
Total 
Volume 
Clinical Safety Labsc 
4.5 
4.5 
 
4.5 
4.5 
 
4.5 
4.5 
18-27 
PD Biomarker Panel 
15d 
17e 
 
17e 
17e 
 
17e 
17e 
68-100 
PD Insulin/Glucose/ 
Cortisol 
 
 
5f 
 
 
5f 
 
 
10 
DNA Testing 
 
 
 
 
 
 
8.5 
 
8.5 
Total Volume by Visit 
(mL) 
19.5 
21.5 
5 
21.5 
21.5 
5 
30 
21.5 
104.5-
145.5 
Total Volume: approximately 104.5-145.5 mL 
 a Day -1 blood draws for clinical labs and PD biomarkers will not be repeated for subjects whose Day -1 Visit is 
≤ 28 days following VBP15-003 Week 24 Final Visit and who had blood drawn for clinical labs and PD biomarkers at 
that Visit. 
b Only subjects who participate in the Dose-tapering Period will have bloods drawn. 
c Hematology, Chemistry, Lipids. 
d cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, ACTH, 
and exploratory PD biomarkers.  
e cortisol, P1NP, osteocalcin, 17- hydroxyprogesterone, testosterone, corticosterone, 11-deoxycortisol, CTX, ACTH, 
HbA1c, and exploratory PD biomarkers.  
f Subjects must have fasted ≥ 6 hours prior to blood draws.  Blood will be drawn prior to administration of the dose of 
study medication. 
 
Section Changed: 
9 Statistical Methods and Planned Analyses 
Paragraph 2 
Original Text: 
This is an open-label extension study with no placebo control.  Historical control data are 
available for the same age range (4-10 years), at largely the same study sites, with the 
same outcome measures.  Untreated natural history control population data is from the 
ongoing CINRG DNHS study of ~400 DMD boys.43,44,45,46  Prednisone-treated historical 
control data is from a clinical trial of prednisone carried out by the CINRG group.47  The 
vamorolone VBP15-LTE Phase IIa extension trial is carried out with daily dosing.  The 
numbers of subjects needed per group to detect significant differences in the 
glucocorticoid effect on efficacy for three gross motor milestone outcomes (TTSTAND, 
TTRW, TTCLIMB) for observed changes and for conservative change estimates (100%, 
80% or 60% of that observed with daily glucocorticoids), respectively, are shown in 

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Table 14.  The numbers of subjects needed per group to detect significant differences in 
the glucocorticoid effect on safety for BMI z-score for observed changes and for 
conservative change estimates, respectively, are also shown in Table 14.   
Vamorolone is not anticipated to show an increase in BMI. 
Table 14 
6-month and 12-month Changes in Outcomes in 4-<8 year-old DMD 
Boys 
 
Notes: a) All patients are 4-<8 years of age at study start. 
b) Data from untreated subjects in the CINRG DMD Natural history study43,44,45,46 data from treated subjects 
in the CINRG Prednisone trial.47  
c) Compares all only daily dose prednisone-treated patients to untreated patients. 
d) All calculations assume a repeated measures ANOVA model with one pre- and one post-measurement.  
Correlation between repeated measures used as follows:  0.75 for height changes, 0.70 for 6 month BMI 
changes, and 0.65 for 12 month BMI changes, and 0.575 for 6 and 12 month velocity changes.  
Power = 0.80 and alpha = 0.025 for all calculations to account for multiple group comparisons (i.e. two 
vamorolone doses, each compared to prednisone for safety and placebo for efficacy). 
^  Conservative change estimates were defined as follows: For BMI, the expected change in vamorolone was set to 
0.0 rather than the observed decrease.  For timed tests, the expected change in vamorolone was set to 80% of the 
observed change in the prednisone group. 
^^ Conservative change estimates were defined as follows: For timed tests, the expected change in vamorolone was 
set to 60% of the observed change in the prednisone group (with SD at 80%). 
 
Revised Text: 
This is an open-label extension study with no placebo control.  Historical control data are 
available for the same age range (4-10 years), at largely the same study sites, with the 
same outcome measures.  Untreated natural history control population data is from the 
ongoing CINRG DNHS study of ~400 DMD boys.44,45,46,47  Prednisone-treated and 
deflazacort-treated historical control data are from a clinical trial of daily dosing of 
prednisone and deflazacort.48  The vamorolone VBP15-LTE Phase IIa extension trial is 
carried out with daily dosing.   

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Section Changed: 
9.2 Analysis Populations 
Original Text: 
All analyses will be based on the actual treatment each subject received.  Four 
populations will be defined for data analysis. 
Revised Text: 
Four populations will be defined for data analysis. 
Section Changed: 
9.2 Analysis Populations 
9.2.2, 9.2.3, 9.2.4 
Original Text: 
9.2.2 Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in the 
VBP15-LTE extension study and have at least one post-baseline assessment will be 
included in the FAS.  The FAS is the primary analysis population for efficacy and PD 
assessments.  This is the mITT population, with the additional requirement to have at 
least one post-baseline assessment.  Subjects who receive at least one dose of vamorolone 
but never have post-baseline assessments will be excluded. 
9.2.3 Control Population DNHS Study 
The control population from the DNHS study will include all study subjects who were 
observed as part of the study in ages ≥ 4 years and <10 years of age at a start of an 
interval of observation and observed for at least one year.  Further, the subjects need to 
have had at least two visits in a time interval of no more than 15 months (e.g., Month 24 
and Month 36 of observation for a subject who entered at age 2 or 3).  The subject should 
have been able to walk independently without assistive devices at the start of the interval 
and should have been able to complete the TTSTAND.  The subject should not have had 
any history of disease or impairment or medications that would have made him ineligible 
to receive the vamorolone intervention as defined by the Phase IIa extension study 

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VBP15-LTE exclusion criteria.  The subject should have been glucocorticoid-naïve for 
the entire interval considered in the control population for this study and should not have 
begun any investigational treatment for the interval considered for the control 
comparison.  Finally, the control intervals to be considered should have the study 
outcomes of TTSTAND, TTCLIMB, TTRW, NSAA, 6MWT and QMT measured.  It is 
acceptable if the participant had progressive disease and could not perform a 
measurement at a later point in the interval; this will be a velocity zero. 
9.2.4 Control Population Prednisone Study 
The control population from the prednisone study will include all subjects who were 
younger than 10 years old at entry and who were randomized to the daily prednisone arm. 
Revised Text: 
9.2.2 Full Analysis Set (FAS) 
All subjects who receive at least one dose of vamorolone study medication in the 
VBP15-LTE extension study and have at least one post-baseline assessment will be 
included in the FAS.  The FAS is the primary analysis population for efficacy and PD 
assessments.  The FAS is the mITT population, with the additional requirement of having 
at least one post-baseline assessment.  Subjects who receive at least one dose of 
vamorolone but never have post-baseline assessments will be excluded. 
9.2.3 Control Population DNHS Study 
The control population from the CINRG Duchenne Natural History Study will include all 
subjects who were observed as part of the study in ages ≥ 4 years and <7 years of age at a 
start of an interval of observation; observed for at least two years with TTSTAND, 
TTCLIMB, TTRW, NSAA, 6MWT and QMT measured; remained glucocorticoid-naive 
during the entire observation period; and were able to walk independently without 
assistive devices, able to complete the TTSTAND; and lacked any history of disease, 
impairment, or medications that would have made them ineligible to receive the 
vamorolone intervention as defined by the VBP15-LTE exclusion criteria at the start of 
the interval.   
9.2.4 Control Population FOR DMD Study 

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The control population from the FOR DMD study will include all subjects who were 4-7 
years old at entry and who were randomized to the daily prednisone or daily deflazacort 
arm.48 
Section changed: 
9.6 Statistical Analyses 
9.6.1, 9.6.2, 9.6.3, 9.6.4 
Original Text: 
9.6.1 General Considerations 
Statistical analyses will be performed using SAS®. 
All measurements will be analyzed based upon the type of distribution, and descriptive 
statistics will be presented by treatment group and assessment time point, as appropriate.  
Descriptive statistics for continuous variables (number [N], mean, median, standard 
deviation [SD], minimum, and maximum), descriptive statistics for categorical variables 
(N and percentage), and individual subject profiles will be presented, as appropriate. 
Baseline measurement is defined as the last non-missing value prior to the first dose of 
study drug in the VBP15-LTE extension study. 
9.6.2 Subject Disposition, Demographics, and Baseline Characteristics 
Subject disposition will be summarized by analysis population.  The number of subjects 
enrolled, the number in each population, and the reason for discontinuation from the 
study will be summarized. 
Subject demographics (e.g., age, race, and ethnicity) and baseline characteristics 
(e.g., height, weight, and months/years since DMD diagnosis) will be summarized 
descriptively by analysis population.  Listings of individual subject data sorted by dose 
group will be reviewed for any differences among the dose groups. 
9.6.3 Safety Analyses 
All subjects who received at least one dose of vamorolone (Safety Population) will be 
included in the safety analyses.  In general, descriptive statistics for each safety endpoint 
will be presented by dose level, while individual subject listings of safety endpoints, 

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sorted by dose group, will be reviewed for any evidence of dose-related differences or 
trends in the safety profile of vamorolone. 
All safety data will be listed. 
Baseline measurement is defined as the non-missing value of the core study VBP15-003 
final visit or last non-missing value prior to first administration of study drug in the 
VBP15-LTE extension study. 
All evaluations of clinical safety will be listed with descriptive statistics presented by 
treatment group.  The primary safety variable will be BMI z-score and will be assessed 
using the same type of statistical models used for efficacy.  Additional secondary safety 
data will include height z-score, blood pressure, and ECG results.  As no change in blood 
pressure or cardiac results is expected, these data will be analyzed using an analysis of 
covariance (ANCOVA) approach which includes the baseline value for each 
measurement as a covariate.  Changes in height z-scores, for which an observed change is 
expected, will be modelled using a linear mixed effects model.  Continuous, quantitative 
laboratory values will be analyzed similar to BMI z-scores.  Categorized laboratory 
values and presence or absence of AEs will be compared using an exact chi-square test. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The incidence of AEs will be summarized overall and by dose level, SOC 
and preferred term; dose level, SOC, preferred term, and intensity (CTCAE grade); and 
dose level, SOC, preferred term, and relationship to study drug.  Additional AE analyses 
will be at the subject level: the number of subjects who had any AE, the distribution of 
number of AEs per subject within a dose level, worst intensity in a subject within a dose 
level, highest level of relationship to study treatment for each subject within a dose level. 
Additional hypotheses of safety will include similar linear modelling with the secondary 
and exploratory outcomes. 
Physical examination results will be listed only. 
9.6.4 Clinical Efficacy and Pharmacodynamic Analyses 
The evaluations of clinical efficacy and PD will be performed using the FAS Population. 

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The primary efficacy outcome is the time to stand from supine velocity (TTSTAND).  
Secondary efficacy outcomes are the NSAA assessment, time to climb four stairs 
(TTCLIMB), time to run/walk 10 meters (TTRW), Quantitative Muscle Testing (QMT), 
and the distance walked in 6 minutes (6MWT).  The primary outcome will be compared 
between vamorolone and historical untreated controls using a mixed-effects linear model 
with treatment group.  Age at study entry will be included as a covariate.  The initial 
model will combine vamorolone doses and a subsequent secondary model will look at 
each dose in comparison to untreated natural history controls.  This will allow the testing 
of whether vamorolone in general and vamorolone at individual doses have significant 
effects on the slope of the velocity.  Additional hypotheses of efficacy will include 
similar linear modelling with the secondary outcomes.  They will also include differing 
comparison groups including untreated natural history controls. 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover 
will be assessed.  Longitudinal analysis of PD biomarkers will be studied as a function of 
treatment, with comparison to prednisone-treated and untreated historical controls, as 
appropriate. 
Individual clinical efficacy and PD data will be listed. 
Revised Text: 
9.6.1 General Considerations 
Statistical analyses will be performed using SAS®. 
All measurements will be analyzed based upon the type of distribution, and descriptive 
statistics will be presented by treatment group and assessment time point, as appropriate.  
Descriptive statistics for continuous variables (number [N], mean, median, standard 
deviation [SD], minimum, and maximum), descriptive statistics for categorical variables 
(N and percentage), and individual subject profiles will be presented, as appropriate. 
All statistical tests will be performed at the 0.05 level.  Paired t-tests will be utilized for 
select variables.  When available, baseline from the VBP15-002 will be utilized when 
calculating change from baseline. 

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9.6.2 Subject Disposition, Demographics, and Baseline Characteristics 
Subject disposition will be summarized by analysis population.  The number of subjects 
enrolled, the number in each population, and the reason for discontinuation from the 
study will be summarized. 
Subject demographics (e.g., age, race, and ethnicity) and baseline characteristics 
(e.g., height, weight, and months/years since DMD diagnosis) will be summarized 
descriptively by analysis population.   
9.6.3 Safety Analyses 
All subjects who received at least one dose of vamorolone (Safety Population) will be 
included in the safety analyses.  In general, descriptive statistics for each safety endpoint 
will be presented by combined vamorolone dose level, individual dose levels, and other 
combinations of dose levels. 
All safety data will be listed. 
Safety data will include BMI (raw units and z-score), height (raw units and z-score), vital 
signs, clinical laboratory test results, spine x-ray results (spine fractures), hand x-ray 
results (bone age), and ECG results.   
Changes in BMI z-score and height z-score will be analyzed using the same type of 
statistical models used for efficacy with vamorolone being compared with the daily 
prednisone and the daily deflazacort arms from the FOR DMD study.  Hand x-ray and 
spine x-ray results will also be compared with the daily prednisone and the daily 
deflazacort arms from the FOR DMD study.   
Adverse events will be summarized overall and by dose level by system organ class 
(SOC) and preferred term (using the Medical Dictionary for Regulatory Activities 
[MedDRA]); by relationship to study medication; and by intensity (CTCAE grade).   
Physical examination results will be listed only. 
9.6.4 Clinical Efficacy and Pharmacodynamic Analyses 
The evaluations of clinical efficacy and PD will be performed using the FAS Population. 

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The primary efficacy outcome is TTSTAND (velocity).  Secondary efficacy outcomes are 
the NSAA assessment, TTCLIMB, TTRW, QMT, and the 6MWT.  TTSTAND, 
TTCLIMB, and TTRW will be analyzed using raw scores and velocity.   
The primary outcome is TTSTAND (velocity) change from VBP15-002 study baseline to 
Month 24 and will be compared between vamorolone and historical untreated controls 
using a restricted maximum likelihood (REML)-based mixed model for repeated 
measures (MMRM).  This model will include fixed effects for treatment, visit, baseline 
TTSTAND velocity (from the VBP15-002 study), age at study entry, and the treatment-
by-visit interaction.  The initial model will compare combined vamorolone doses to 
untreated natural history controls and subsequent secondary models may compare 
individual and other combinations of dose levels to untreated natural history controls.  
The secondary outcome measures will be compared using similar models.  Full details 
will be provided in the Statistical Analysis Plan (SAP).   
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover 
will be assessed, as well as exploratory biomarkers of safety and efficacy.  Biomarkers 
will be summarized descriptively over time. 
Individual clinical efficacy and PD data will be listed. 
Section changed: 
10.5 Study Monitoring 
Paragraph 1 
Original Text: 
10.5 
Study Monitoring 
In accordance with applicable regulations, GCP, and the procedures of the Sponsor or its 
designees, the Study Monitor will periodically contact the site and conduct on-site visits.  
The extent, nature, and frequency of on-site visits will be based on enrollment rate and 
data quality at the site.  Through frequent communications (e.g., letter, e-mail, and 
telephone), the Study Monitor will ensure that the investigation is conducted according to 
protocol and regulatory requirements. 
Revised Text: 

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10.5 
Data and Safety Monitoring Board (DSMB) and Other Study Monitoring 
10.5.1 DSMB 
An unblinded Data and Safety Monitoring Board (DSMB), operating autonomously from 
the Sponsor and the site investigators, will be responsible for providing independent 
recommendations to the Sponsor about risk-benefit of the study and for any modification 
affecting safety or data integrity required during the course of the study.  The DSMB 
members must not be actively involved in study design, conduct or daily management of 
this study and must not have financial, proprietary, professional, or other interests that 
may affect impartial, independent decision-making.  
Specialists may be invited to participate as non-voting members at any time if additional 
expertise is desired.  The DSMB will formally interact with the Sponsor through the 
sharing of DSMB meeting minutes.  
The DSMB will be responsible for: 
• 
Examining accumulating safety and other relevant data at pre-specified points 
during the course of the study in order to make recommendations concerning 
continuation, termination, or modification of the study; 
• 
Examining accumulating clinical efficacy data and comparing to corticosteroids 
and an untreated historical control group in order to make recommendations 
concerning continuation, termination, or modification of the study; 
• 
Reviewing protocol violations; 
• 
Providing expert advice to the Sponsor on an ad hoc basis regarding matters such 
as safety concerns or diagnostic evaluations in individual subjects; 
• 
Based on the results of its deliberations, the DSMB can recommend continuation 
of the study unchanged, study interruption, study termination, modification of the 
studies, or alteration in the DSMB monitoring plan. 
10.5.2 Study Monitoring 
In accordance with applicable regulations, GCP, and the procedures of the Sponsor or its 
designees, the Study Monitor will periodically contact the site and conduct on-site visits.  

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The extent, nature, and frequency of on-site visits will be based on enrollment rate and 
data quality at the site.  Through frequent communications (e.g., letter, e-mail, and 
telephone), the Study Monitor will ensure that the investigation is conducted according to 
protocol and regulatory requirements. 
Section Changed: 
13 References 
Original Text: 
29. 
Investigator’s Brochure, Version 3, Vamorolone (17α,21-dihydroxy-16α-methyl-
pregna-1,4,9(11)-triene-3,20-dione) 4% Oral Suspension, ReveraGen BioPharma, 
Inc., January 23, 2016. 
Revised Text: 
29. 
Investigator’s Brochure, Version 8, Vamorolone (17α,21-dihydroxy-16α-methyl-
pregna-1,4,9(11)-triene-3,20-dione) 1.33% and 4% Oral Suspension, ReveraGen 
BioPharma, Inc., September 24, 2018. 
Original Text: 
42. 
Hathout Y, Brody E, Clemens PR, et al. Large-scale serum protein biomarker 
discovery in Duchenne muscular dystrophy. Proc Natl Acad Sci USA. 2015; 
112(23): 7153-8. 
43. 
Bello L, Kesari A, Gordish-Dressman H, et al. Genetic modifiers of ambulation in 
the Cooperative International Neuromuscular Research Group Duchenne natural 
history study. Ann Neurol. 2015; 77(4):684-696. 
Revised Text: 
42. 
Hathout Y, Brody E, Clemens PR, et al. Large-scale serum protein biomarker 
discovery in Duchenne muscular dystrophy. Proc Natl Acad Sci USA. 2015; 
112(23): 7153-8. 
43. 
Conklin LS, Damsker JM, Hoffman EP, et al. Phase IIa trial in Duchenne muscular 
dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-
inflammatory drug. Pharmacol. Res. 2018 Sep 13; 136:140-50. 
44. 
Bello L, Kesari A, Gordish-Dressman H, et al. Genetic modifiers of ambulation in 
the Cooperative International Neuromuscular Research Group Duchenne natural 
history study. Ann Neurol. 2015; 77(4):684-696. 
Original Text: 

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47. 
Escolar DM, Hache LP, Clemens PR, et al. Randomized, blinded trial of weekend 
vs. daily prednisone in Duchenne muscular dystrophy. Neurology. 2011; 
77(5):444-452. 
Revised Text: 
48. 
Guglieri M, Bushby K, McDermott MP, et al. Developing standardized 
corticosteroid treatment for Duchenne muscular dystrophy. Contempt. Clin. Trials. 
2017 Jul; 58:34-39.