A Phase II Open-Label, Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD)
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Sponsor: Santhera Pharmaceuticals

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 1 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
Amendment #3 for a Phase II Open-Label, Multiple 
Dose Study to Assess the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamics, and 
Exploratory Efficacy of Vamorolone in Boys Ages 2 to 
<4 Years and 7 to <18 Years with Duchenne Muscular 
Dystrophy (DMD) 
Protocol Number: 
VBP15-006 
Document Number: 
VBP15-006-A3 (Version 1.0) 
FDA IND No.: 
118,942 
Investigational Product: 
Vamorolone 
Sponsor:   
Santhera Pharmaceuticals (Switzerland) Ltd 
Hohenrainstrasse 24 
4133 Pratteln 
Switzerland 
Prinicipal Investigator 
Jean Mah, M.D 
 
Email: 
 
Medical Monitor: 
 
 
Email: 
 
Document Date: 
11 April 2023 
 
This document represents proprietary information belonging to Santhera Pharmaceuticals Ltd.  
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. 
PI
PI
PI

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 2 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
SIGNATURES OF AGREEMENT FOR VBP15-006 
Amendment #3 for a Phase II Open-Label, Multiple Dose Study to Assess the Safety, 
Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of 
Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years with Duchenne 
Muscular Dystrophy (DMD) 
 
Reviewed and Approved by: 
 
 
 
 
 
Santhera Pharmaceuticals (Switzerland) Ltd 
 
Date 
 
PI
PI
PPD

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 3 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
INVESTIGATOR PROTOCOL AGREEMENT 
Amendment #3 for a Phase II Open-Label, Multiple Dose Study to Assess the 
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory 
Efficacy of Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years with 
Duchenne Muscular Dystrophy (DMD) 
PROTOCOL NUMBER: 
VBP15-006 
SPONSOR: 
Santhera Pharmaceuticals (Switzerland) Ltd 
DOCUMENT DATE: 
11 April 2023 
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 Santhera Pharmaceuticals (Switzerland) Ltd.  
I agree to conduct the study according to this protocol and the obligations and requirements 
of clinical Investigators and all other requirements set out in the Declaration of Helsinki 
listed in 21 CFR part 312, and ICH principles of Good Clinical Practice (GCP) and in 
accordance with all applicable laws, guidances and directives of the jurisdiction where the 
study is being conducted.  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 Santhera Pharmaceuticals (Switzerland) 
Ltd 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 
Santhera Pharmaceuticals (Switzerland) Ltd. 
For protocol amendments, I agree not to implement the amendment without agreement from 
Santhera Pharmaceuticals (Switzerland) Ltd 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 (WET-INK OR VALIDATED E-SIGNATURE) SIGNED 
AGREEMENT AT YOUR SITE AND SEND A SCANNED COPY OF THE SIGNED 
ORIGINAL TO SANTHERA PHARMACEUTICALS (SWITZERLAND) LTD, OR 
DESIGNEE 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 4 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
SERIOUS ADVERSE EVENT CONTACT INFORMATION 
In the event of a serious adverse event (SAE) (see Section 7.6.6), the Investigator will 
complete the SAE 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 ICON safety management team within 24 hours, using the 
contact information below:  
In United States and Canada: 
 
Email: CHOSafety@iconplc.com 
 
Drug Safety Fax: 1 888 772 6919 or 1 434 951 3482 
 
SAE Questions: Drug Safety Helpline: 1 800 772 2215  
In Europe, Asia, Pacific, Africa and Australia: 
  
 
Email: MHGSafety@iconplc.com 
 
Drug Safety Fax: +44 1792 525720 
 
SAE Questions: Drug Safety Helpline: +49 621 878 2154 
 
 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 5 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
PROTOCOL AMENDMENT TRACKING 
Document 
Document Number 
Approval Date 
Original Protocol 
VBP15-006 
14 October 2021 
Amendment #1 
VB15-006-A1 (Version 1.1) 
14 April 2022 
Amendment #2 
VB15-006-A2 (Version 1.0) 
09 February 2023 
Amendment #3 
VB15-006-A3 (Version 1.0) 
11 April 2023 
 
Reasons for Protocol Amendment #3: 
PPD, the central laboratory was providing an EDTA-1ML K2 (Plastic) tube for collection 
of specific samples. However the manufacturer of this item has informed PPD that they 
are discontinuing the manufacture of this item globally, effective immediately. As such 
and since there is no equivalent tube with 1 mL volume, PPD needs to replace it with an 
alternate tube EDTA-1.2 mL S-Monovette K2 (Plastic). As a consequence, the volumes 
of blood collected at the study visits need to be revised. 
The following changes have been included in this amendment and will be implemented 
following the standard approval process: 
x Replace the 1 mL EDTA blood sampling tube by the 1.2 mL and revise the 
sampling plan (HbA1c is analyzed from the hematology sample). 
Reasons for Protocol Amendment #2: 
The following changes have been included in this amendment and will be implemented 
following the standard approval process: 
x To make editorial modifications regarding transfer of Sponsor from ReveraGen 
BioPharma, Inc. to Santhera Pharmaceutical (Switzerland) Ltd. 
x To update section 1 following Investigator’s Brochure revision (version 12) 
x To update the reference list 
x To update Dosing Recommendation for children weighing 50 kg or more 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 6 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
x To describe the procedure of the dose tapering after discontinuation of 
vamorolone  
x To include ambulatory status recording as part of physical examination at 
Baseline 
x To define a new age subgroup (12 to <18 years) in which 10 additional 
glucocorticoid-treated subjects will be recruited, to the vamorolone daily dose of 
6 mg/kg and to add exploration of the gonadal and thyroid axis biomarkers in this 
subgroup. To update the total number of participating subjects accordingly. 
x To clarify that date of birth may be collected where local regulations allow. 
Reasons for Protocol Amendment #1  
x To clarify vamorolone is a 4.0% wt/vol suspension and provide details of 
vamorolone packaging  
x To clarify that age of enrollment will be collected and date of birth will not 
x To clarify standing height will be measured in all participants who can stand 
independently 
x To remove glutamate dehydrogenase (GLDH) from laboratory evaluations 
x To clarify vamorolone administration will take place at the study site during the 
Week 6 visit  
x To specify subjects should be fasted ≥6 hours prior to all study visits when blood 
will be drawn 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 7 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
STUDY SYNOPSIS 
Protocol Title 
A Phase II Open-label, Multiple Dose Study to Assess the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone 
in Boys Ages 2-<4 Years and 7-<18 Years with Duchenne Muscular Dystrophy 
(DMD) 
Name of Sponsor 
Santhera Pharmaceuticals (Switzerland) Ltd 
Protocol Number 
VBP15-006 
Drug Substance 
17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione 
Investigational 
Drug Product 
Vamorolone, 4.0% weight per volume (wt/vol) suspension for oral dosing 
Phase of 
Development 
Phase II 
Indication 
Treatment of Duchenne muscular dystrophy (DMD) 
Primary Objective 
To evaluate the safety and tolerability of vamorolone administered orally at daily 
doses of 2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period in boys ages 
2 to <4 and 7 to <18 years with DMD.  
Secondary 
Objectives 
1. To evaluate the pharmacokinetics (PK) of vamorolone administered orally in 
boys ages 2 to <4 and 7 to <18 years with DMD. 
2. To confirm the vamorolone exposure in boys ages 2 to < 4 and 7 to <18 years 
with DMD at 2.0 and 6.0 mg/kg and to adjust the doses if appropriate to 
achieve similar vamorolone areas under the concentration-time curve 
(AUCs) across the entire pediatric age range. 
Exploratory 
Objectives 
1. To compare the efficacy, as measured by the effect on muscle function, of 
vamorolone administered orally at daily doses of 2.0 mg/kg versus 
6.0 mg/kg over a 3-month treatment period in boys ages 2 to <4 and 7 to 
<18 years with DMD; 
2. To evaluate the effect of vamorolone administered orally at daily doses of 2.0 
mg/kg and 6.0 mg/kg over a 3-month treatment period on behavior and 
neuropsychology in boys ages 2 to <4 and 7 to <18 years with DMD;  
3. To evaluate the effect of vamorolone administered orally at daily doses of 2.0 
mg/kg and 6.0 mg/kg over a 3-month treatment period on physical 
functioning in boys ages 2 to <4 and 7 to <18 years with DMD; 
4. To evaluate the ease of administration of vamorolone in boys ages 2 to <4 
years with DMD and study medication acceptability of vamorolone in boys 
ages 7 to <18 years with DMD at daily oral doses of 2.0 mg/kg and 
6.0 mg/kg; 
5. To investigate the effects of vamorolone administered orally at daily doses of 
2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period on 
pharmacodynamic (PD) biomarkers of safety and efficacy in boys ages 2 to 
<4 and 7 to <18 years with DMD. 
Study Design 
This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, pharmacokinetic (PK), PD, clinical efficacy, behavior and 
neuropsychology, and physical functioning of vamorolone administered orally at 
daily doses of 2.0 mg/kg and 6.0 mg/kg over a treatment period of 3 months in 
steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated and currently 
untreated boys ages 7 to <18 years with DMD.  

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 8 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day 
Pretreatment Baseline Period; a 3-month open-label Treatment Period (Weeks 
1-12); and a -week Dose-tapering Period for subjects who will not transition 
directly to further vamorolone or standard of care (SoC) glucocorticoid treatment 
at the end of the study. 
Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent and assent, as required, is obtained.   
x 
Within the 2 to <4 years age group, the initial 10 eligible subjects will 
be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 
Visit.  The subsequent 10 eligible subjects will be assigned to the 6.0 
mg/kg/day treatment group at the Baseline Day -1 Visit. 
x 
Within the 7 to <18 years age group (including an additional 12 to 
<18 years age group), both corticosteroid-treated and untreated, the 
initial 12 eligible subjects will be assigned to the 2.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit.  The subsequent 22 
eligible subjects (including 10 subjects from an additional 12 to <18 
years age group) will be assigned to the 6.0 mg/kg/day treatment group 
at the Baseline Day -1 Visit. 
The first 6 subjects in each age group at 2.0 mg/kg will serve as the PK/safety 
run-in cohorts. PK assessments will be performed at week 2, and together with 
the safety assessment during the first 4 weeks of treatment, will be the basis to 
confirm whether 2.0 and 6.0 mg/kg/day will be used in the subsequent patients 
or if a dose adjustment is needed to avoid over or under-exposure of vamorolone 
in patients for any of the two age groups. 
Glucocorticoid-treated subjects in the 7 to <18 years age group will take their 
final dose of SoC glucocorticoid therapy for DMD on Baseline Day -1, within 24 
hours prior to administration of the first dose of vamorolone study medication.   
All subjects will begin their assigned vamorolone treatment on Treatment Period 
Day 1 and will continue to receive their assigned vamorolone treatment 
throughout the duration of the 3-month Treatment Period (Weeks 1-12). 
At the end of the 3-month Treatment Period (Week 12), subjects will be given 
the option to receive vamorolone in an expanded access or compassionate use 
program, if possible, or to transition to SoC treatment for DMD (may include 
glucocorticoids).   
Subjects completing VBP15-006 and enrolling directly into the expanded access 
or compassionate use program or transitioning directly to SoC glucocorticoid 
treatment will not need to taper their vamorolone dose prior to participation in 
the expanded access or compassionate use program or initiation of SoC 
glucocorticoid treatment.   
All subjects who will not transition directly to further vamorolone or SoC 
glucocorticoid treatment will begin the dose tapering period during which the 
dose of study medication will be progressively reduced and discontinued. 
Planned Sample 
Size 
A total of approximately 20 subjects will enrolled within the 2 to <4 years age 
group, as follows: 
x 
Vamorolone 2.0 mg/kg/day (n=10); enrolled first 
x 
Vamorolone 6.0 mg/kg/day (n=10); enrolled after previous dose group 
A total of approximately 34 subjects will be enrolled to treatment within the 7 to 
<18 years age group, with 2.0 mg/kg/day groups enrolled first, as follows: 
x 
Vamorolone 2.0 mg/kg/day, steroid untreated at entry (n=6) 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 9 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
x 
Vamorolone 2.0 mg/kg/day, steroid treated at entry (n=6) 
x 
Vamorolone 6.0 mg/kg/day, steroid untreated at entry (n=6) 
x 
Vamorolone 6.0 mg/kg/day, steroid treated at entry (n=6)  
x 
Vamorolone 6.0 mg/kg/day, 12 to <18 years and steroid treated at entry 
(n=10; additional group) 
Inclusion Criteria 
1. Subject’s parent(s) or legal guardian(s) has (have) provided written informed 
consent and Health Insurance Portability and Accountability Act (HIPAA) 
authorization, where applicable, prior to any study-related procedures; 
participants will be asked to give written or verbal assent according to local 
requirements; 
2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) 
diagnosis of DMD, defined as: 
a. 
Dystrophin immunofluorescence and/or immunoblot showing complete 
dystrophin deficiency, and clinical picture consistent with typical 
DMD, OR 
b. Identifiable mutation within the DMD gene (deletion/duplication of one 
or more exons), where reading frame can be predicted as ‘out-of-
frame,’ and clinical picture consistent with typical DMD, OR 
c. 
Complete dystrophin gene sequencing showing an alteration (point 
mutation, duplication, other) that is expected to preclude production of 
the dystrophin protein (i.e., nonsense mutation, deletion/duplication 
leading to a downstream stop codon), with a clinical picture consistent 
with typical DMD; 
3. Subject is male, 2 to <4 years or 7 to <18 years of age at time of enrollment 
in the study; 
4. If 7 to <18 years of age and currently taking standard of care glucocorticoids  
for treatment of DMD, subject has been taking standard of care 
glucocorticoids at stable dose for at least 3 months prior to enrollment in the 
study and will continue the same stable dose regimen through the date of the 
Baseline Day -1 Visit.  [Note: Inhaled and/or topical glucocorticoids are 
permitted if last use is at least 4 weeks prior to enrollment or if administered 
at stable dose beginning at least 4 weeks prior to enrollment and anticipated 
to be used at the stable dose regimen for the duration of the study]; 
5. If 7 to <18 years of age, and not currently glucocorticoid-treated, subject has 
not received oral glucocorticoids or other oral immunosuppressive agents 
for at least 3 months prior to enrollment.  [Note: Inhaled and/or topical 
glucocorticoids are permitted if last use is at least 4 weeks prior to 
enrollment or if administered at stable dose beginning at least 4 weeks prior 
to enrollment and anticipated to be used at the stable dose regimen for the 
duration of the study]; 
6. Clinical laboratory test results are within the normal range at the Screening 
Visit, or if abnormal, are not clinically significant, in the opinion of the 
Investigator. [Notes: Serum gamma glutamyl transferase (GGT), creatinine, 
and total bilirubin all must be ≤ upper limit of the normal range at the 
Screening Visit.  An abnormal vitamin D level that is considered clinically 
significant will not exclude a subject from participating]; 
7. Subject has evidence of chicken pox immunity as determined by: 
x 
Presence of IgG antibodies to varicella, as documented by a positive test 
result from the local laboratory from blood collected during the 
Screening Period; OR 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 10 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
x 
Documentation, provided at the Screening Visit, that the subject has had 
2 doses of varicella vaccine, with or without serologic evidence of 
immunity; the second of the 2 immunizations must have been given at 
least 14 days prior to assignment to a dose group; 
8. Subject and parent(s)/guardian(s) are willing and able to comply with 
scheduled visits, study drug administration plan, and study procedures. 
Exclusion Criteria 
1. Subject has current or history of major renal or hepatic impairment, diabetes 
mellitus or immunosuppression; 
2. Subject has current or history of chronic systemic fungal or viral infections; 
3. Subject has used mineralocorticoid receptor agents, such as spironolactone, 
eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate 
potassium), or mexrenone (mexrenoate potassium) within 4 weeks prior to 
enrollment; 
4. Subject has a history of primary hyperaldosteronism; 
5. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic 
cardiac abnormality on investigation would not be exclusionary];  
6. If 2 to <4 years of age, 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 1 month cumulative, with last 
use at least 3 months prior to enrollment, will be considered for eligibility 
on a case-by-case basis, unless discontinued for intolerance.  Inhaled and/or 
topical glucocorticoids are permitted if last use is at least 4 weeks prior to 
enrollment or if administered at stable dose beginning at least 4 weeks prior 
to enrollment and anticipated to be used at the stable dose regimen for the 
duration of the study]; 
7. Subject has an allergy or hypersensitivity to the study medication or to any of 
its constituents; 
8. Subject has used idebenone within 4 weeks prior to enrollment; 
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 taking (or has taken within 4 weeks prior to enrollment) herbal 
remedies and supplements which can impact muscle strength and function 
(e.g., Co-enzyme Q10, creatine, etc);  
12. Subject is taking (or has taken within 3 months prior to enrollment) any 
medication indicated for DMD, including Exondys51, Exondys53, 
Exondys45, Viltepso and Translarna;  
13. Subject has been administered a live attenuated vaccine within 14 days prior 
to the first dose of study medication; 
14. Subject is currently taking any other investigational drug or has taken any 
other investigational drug within 3 months prior to enrollment;  
15. Subject has previously been enrolled in the VBP15-006 study or any other 
vamorolone study. 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 11 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
Note: Any parameter/test may be repeated at the Investigator’s discretion during 
Screening to determine reproducibility.  In addition, subjects may be rescreened 
if ineligible due to negative anti-varicella IgG antibody test result.  
Number of Centers 
The study will be conducted at approximately 6 Canadian study sites. 
Study Period 
First subject screened: 4Q 2021 
Last subject last visit: 1Q 2024 
Study Duration  
Approximately 24 months total duration 
Individual Subject 
Study Duration 
Up to approximately 21 weeks: 
x 
Screening Period: up to 5 weeks 
x 
Baseline Period: 1 day 
x 
Treatment Period: 12 weeks (Weeks 1-12) 
x 
Dose-tapering Period: 4 up to 8  weeks, only for subjects who will not 
transition directly to further vamorolone or SoC glucocorticoid treatment 
at the end of the study.  
Subjects who complete the Treatment Period Week 12 assessments will be given 
the option of continuing vamorolone treatment by expanded access or 
compassionate use, if possible, under separate protocol.  Subjects who continue 
directly with vamorolone treatment by expanded access or compassionate use or 
who transition directly to SoC glucocorticoid treatment for DMD will be 
discharged from the VBP15--006 study following completion of all Week 12 
assessments and will not participate in the Dose--tapering Period. 
Study Drug 
Formulation, 
Dosage & 
Administration 
Treatment Period and Dose-tapering Period 
Subjects will be administered 4.0% wt/vol oral suspension (Formulation route of 
synthesis 2 [ROS2]).   
The planned vamorolone doses are 2 mg/kg and 6 mg/kg daily. The initial 
patients enrolled in each age group will receive 2 mg/kg/day to confirm the PK 
and safety of vamorolone in both age groups at this dose level. After review of 
the PK and safety data from at least 6 patients in each age cohort, subsequent 
patients can be enrolled at the 6 mg/kg /day dose level. If the intended dose of 
vamorolone is 6 mg/kg/day, AND patients weigh 50 kg or more, the daily dose 
should be capped at 300mg. Considering the linearity of vamorolone 
pharmacokinetics, if the intended patient dose is 2mg/kg/day, the dose is capped 
at 100mg per day for patients weighing 50kg or more.. All subjects: vamorolone 
4.0% wt/vol oral suspension (investigational medicine) will be administered 
once daily over the 12-week Treatment Period (Weeks 1-12) and during the 
Dose-tapering Period, if applicable.   
The oral suspension study medication will be administered in the study unit at 
the Day 1, Week 2, and Week 12 study visits; all other doses will be 
administered at home.  Study drug oral suspensions 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.   
Participants must fast ≥6 hours prior to the Day1, Week 2, Week 6 and Week 12 
study visits, when dosing will occur at the study site. The daily dose of study 
medication administered at home should be taken in the morning with breakfast. 
There are no other food or drink restrictions before or after dosing.  

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 12 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
Study Summary 
This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, physical 
functioning, and sleep-wake activity of vamorolone over a treatment period of 
12 weeks in steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated 
and currently untreated boys ages 7 to <18 years with DMD.   
Subjects will be assessed for safety and tolerability, PK, PD, clinical efficacy, 
behavior and neuropsychology, and physical functioning at scheduled visits 
throughout the study.  Screening assessments will be performed prior to 
assignment to a study group.  All subjects will be assigned to treatment at the 
Baseline Day -1 Visit.   
After completion of Screening and Baseline assessments and assignment to 
treatment, subjects will return to the study clinic on Day 1 for safety, PK, and 
PD assessments prior to administration of the first dose of study medication.  
Additional study visits will occur at Week 2, Week 6, and Week 12.  Adverse 
events, including serious adverse events (SAEs), and concomitant medications 
will be recorded throughout the study.  A Data and Safety Monitoring Board 
(DSMB) will review SAEs and other pertinent safety data at regular intervals 
during the study and make recommendations to the Sponsor regarding study 
conduct.   
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their 
final dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and 
switch to their assigned vamorolone treatment, 2.0 mg/kg/day (for participants 
weighing 50kg and over, the dose is capped at 100mg/day) or 6.0 mg/kg/day (for 
participants weighing 50kg and over, the dose is capped at 300mg/day), 
beginning the next day on Treatment Period Day 1.  For all subjects, daily study 
drug dosing during the Treatment Period will occur from the date of the Day 1 
Visit through the date of the Week 12 Visit.  Study drug dosing will occur at 
home on all days except dates of the Day 1, Week 2, Week 6, and Week 12 
Visits, when dosing will occur at the study site. 
Subject diaries will be dispensed at the Day 1, Week 2, Week 6, and Week 12 
(for subjects participating in the Dose-tapering Period) Visits to record AEs, 
changes to concomitant medications taken during the study, and any missed or 
incomplete doses of study medication. 
The scheduled Week 12 assessments may be performed over a 2-day period, if 
necessary, to facilitate scheduling.  The scheduled 12-lead electrocardiogram 
(ECG), eye examination, Pediatric Outcome Data Collection Instrument 
(PODCI), and Personal Adjustment and Role Skills Scale III (PARS III) may be 
completed on the day prior to the final Week 12 dose of study medication; 
alternatively, these assessments may be performed on the date of the final Week 
12 dose of study medication.  The scheduled physical examination, weight, 
height, vital signs, clinical laboratory tests, blood draws for PD biomarker 
analysis, Ease of Study Medication Administration Assessment (2 to <4 years 
only)/Study Medication Acceptability Assessment (7 to <18 years only), 
functional assessments (Bayley-III Gross Motor scale [ages 2 to <4 years] and 
Performance of Upper Limb (PUL) Test [7 to <18 years]), recording of 
AEs/SAEs and concomitant medications, and return of subject diaries should be 
performed on the date of the final Week 12 dose of study medication.   

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Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
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Subjects who complete the VBP15-006 study assessments through the Week 12 
Visit may be given the opportunity to continue to receive vamorolone as part of 
an expanded access or compassionate use program under separate protocol, or 
alternatively transition to SoC treatment (including glucocorticoids) for DMD.  
Standard of care treatment for DMD may be offered to the subject following 
completion of the VBP15-006 study if the subject’s parent(s) or guardian(s) does 
not wish to enroll the subject in the expanded access or compassionate use 
program and/or the Investigator feels it to be in the best interest of the subject.   
Subjects who complete the VBP15-006 study and will enroll directly into the 
expanded access or compassionate use program to continue vamorolone 
treatment or will transition directly onto SoC glucocorticoid treatment for DMD 
will be discharged from the VBP15-006 study following completion of all 
Week 12 assessments.  Subjects who will not continue vamorolone treatment in 
the expanded access or compassionate use program, and who will not transition 
directly to SoC glucocorticoid treatment for DMD, will have their vamorolone 
dose tapered during Dose-tapering Period prior to discharge from the study. . 
Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to 
ensure that the dose tapering is proceeding according to protocol to assess 
potential signs or symptoms of adrenal suppression, and to address any questions 
the parent(s)/guardian(s) may have. 
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 Week 12 Visit should return 
to the study unit for scheduled Week 12 assessments at the time of early 
withdrawal, whenever possible, assuming the subject has not withdrawn consent.  
Any subject who withdraws early from the study after study medication dosing 
has begun and will not transition directly to SoC glucocorticoids should undergo 
dose-tapering following early completion of the Week 12 assessments. 
Safety Measures  
x 
Body Mass Index (BMI) 
x 
Body Mass Index z-score 
x 
Weight and Height (standing height collected for subjects in 2 to <4 
years age group and all participants who can stand independently; height 
calculated from ulnar length in subjects in 7 to <18 years age group) 
x 
Vital signs (sitting blood pressure, heart rate, respiratory rate, and body 
temperature [modality for determining temperature should be consistent 
for each subject at all assessment time points throughout the study]) 
x 
Physical examination, including examination for infections 
x 
Cushingoid features 
x 
Clinical laboratory tests: 
x 
Hematology and clinical chemistry 
x 
Urinalysis 
x 
Lipid profile (triglycerides, total cholesterol, low density lipoprotein 
[LDL], high density lipoprotein [HDL]) 
x 
Vitamin D level 
x 
12-lead electrocardiogram (ECG) 
x 
Eye examination 
x 
Clinical signs and symptoms (AEs and SAEs) 

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Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
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x 
Grading of clinical and clinical laboratory AEs will be according to 
the Common Terminology Criteria for Adverse Events (CTCAE, 
v.5.0) 
Pharmacodynamic 
Measures 
Blood will be collected for serum PD biomarker analysis to evaluate effects of 
vamorolone on biomarkers of safety (i.e., biomarkers associated with insulin 
resistance [fasting glucose and insulin, and hemoglobin A1c {HbA1c}], adrenal 
suppression [morning cortisol], and bone turnover [osteocalcin, C-terminal 
peptide fragment of collagen 1 {CTX}, and aminoterminal propeptide of type I 
collagen {P1NP}]), and additional exploratory biomarkers.  Blood samples for 
analysis of PD biomarkers will be collected prior to the first dose of study 
medication at the Day 1 Visit, and prior to the final dose of study medication at 
the Week 12 Visit.  Blood samples for PD biomarkers will be collected after 
subjects have fasted for ≥ 6 hours, and prior to the daily dose of study 
medication.  
Pharmacokinetic 
Measures 
x 
Blood will be collected for vamorolone PK analysis on Day 1 and Week 
2 visits. 
x 
For ages 2 to <4 years, blood sampling is within 30 minutes prior to and 
1-, 2-, and 6-hours following the first dose of study medication at the 
Day 1 Visit, and within 30 minutes prior to and 1-, 2- and 6- hours 
following the daily dose of study medication at the Week 2 Visit .   
x 
For ages 7 to <18 years, blood sampling is within 30 minutes prior to 
and 1-, 2-, 4-, 6- and 8-hours following the first dose of study medication 
at the Day 1 Visit, and within 30 minutes prior to and 1-, 2-, 4-, 6- and 8-
hours following the first dose of study medication at the Week 2 Visit . 
Clinical Efficacy 
Measures 
x 
Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross 
Motor scale (ages 2 to <4 years only) 
x 
Performance of Upper Limb (PUL) test (ages 7 to <18 years only) 
Patient-reported 
Outcome Measures  
x 
Pediatric Outcome Data Collection Instrument (PODCI) 
x 
Personal Adjustment and Role Skills Scale, ed. 3 (PARS III) 
questionnaire 
x 
Ease of Study Medication Administration Assessment (ages 2 to <4 
years only) 
x 
Study Medication Acceptability Assessment (ages 7 to <18 years only) 
Statistical Methods 
Sample Size: 
This is an open-label, multiple dose study.  Study medication is administered 
daily in this Phase II trial.   

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Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
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For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a 
total of approximately 20 subjects in the 2 to <4 years age group will be enrolled 
with approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 
mg/kg/day).  A total of approximately 34 subjects in the 7 to <18 years age 
group will be enrolled with approximately 12 subjects per dose level group 
(2.0 mg/kg/day and 6.0 mg/kg/day) and each dose level group stratified 1:1 by 
glucocorticoid treatment status at study entry to include approximately 6 subjects 
glucocorticoid-untreated and 6 subjects glucocorticoid-treated at study entry, to 
which 10 subjects 12 to <18 years are added to the 6 mg/kg dose level.  This 
sample size is considered sufficient to detect drug safety concerns in a pediatric 
population ages 2 to <4 and 7 to <18 years with DMD based on clinical 
judgment and prior study of vamorolone at these doses.  In addition, this sample 
size is sufficiently large to determine PK parameters.   
A drop-out rate is not considered; subjects who withdraw early from the study 
may be replaced. 
Analysis Populations:   
Three populations will be defined for data analysis: Safety Population, modified 
Intent-to-Treat Population, and Pharmacokinetic Population. 
Safety Population 
All subjects who receive at least one dose of study medication will be included 
in the Safety Population.  The Safety Population is the primary analysis 
population for safety and PD assessments.  Results will be presented “as 
treated.” 
Modified Intent-to-Treat (mITT) Population 
All subjects who receive at least one dose of study medication and have at least 
one post-baseline efficacy assessment will be included in the mITT Population.  
The mITT Population is the primary analysis population for clinical efficacy.  
Subjects who receive at least one dose of study medication but never have 
post-baseline assessments will be excluded.  Results will be presented “as 
assigned.” 
Pharmacokinetic (PK) Population 
All subjects who receive at least one dose of vamorolone study medication and 
have sufficient data for PK analysis will be included in the PK Population. 
General Statistical Considerations:   
All measurements will be analyzed based upon the type of distribution and 
descriptive statistics presented by age group, vamorolone dose level, 
glucocorticoid treatment status at entry (ages 7 to <18 years only), and time 
point, as appropriate.  No formal interim statistical analyses are planned, apart 
from the interim safety data views and presentations to be created for the DSMB.  
Missing values for safety outcomes will be treated as missing, unless stated 
otherwise.  Individual subject listings of endpoints, sorted by age group, 
vamorolone dose level, and glucocorticoid treatment at entry (ages 7 to <18 
years only) will be reviewed for any evidence of dose-related differences or 
trends. 
Baseline measurement is defined as the last non-missing value prior to the first 
dose of study drug.  
Safety and Tolerability Analyses: 
All evaluations of clinical safety will be listed and presented using descriptive 
statistics by age group, dose level, and time point. Additional summaries will be 
provided by glucocorticoid use (users versus non-users).  

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Protocol No.: VBP15-006 
 
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Safety data will include BMI, weight, height, vital signs, eye examination 
results, and ECG results, and these will be presented using descriptive statistics.  
The BMI and height values will be evaluated both on the original scale and as z-
scores. Safety laboratory data will be summarized using descriptive statistics, 
and out-of-range values will be listed. Furthermore, continuous safety endpoints 
will be evaluated using a Mixed Model for Repeated Measures (MMRM), when 
appropriate. The models will include the baseline value as a covariate and visit, 
dose level, glucocorticoid use (when appropriate) and the relevant interaction 
terms as fixed effects. Separate models will be used for each age group. In case 
of no repeated measures (endpoint is assessed at one post-baseline visit only), 
Analysis of Covariance (ANCOVA) models will be used instead of MMRM. 
Adverse events will be summarized overall and by age group, dose level, 
glucocorticoid treatment at entry (ages 7 to <18 years only), system organ class 
(SOC) and preferred term (using the Medical Dictionary for Regulatory 
Activities [MedDRA]). Further analyses will be conducted by seriousness, 
severity and relationship to study medication. Adverse events leading to 
premature discontinuation of the study will be evaluated separately. 
Pharmacokinetic Analyses: 
For the age 2 to <4 years groups, the pre-dose and 1-, 2-, and 6-hour post-dose 
plasma concentration measurements of vamorolone at Day 1 and Week 2 will be 
assessed. 
For the age 7 to <18 years groups, the pre-dose and 1-, 2-, 4-, 6, and 8-hour post-
dose plasma concentration measurements of vamorolone at Day 1 and Week 2 
will be assessed  
Comparison of drug exposures by age group, dose level, and glucocorticoid 
treatment at entry (ages 7 to <18 years only) will be aggregated with PK data 
from previous studies in DMD boys for comparison across the entire pediatric 
age range and with measurements obtained in healthy adult male subjects.  All 
PK data will be combined in a population assessment of plasma concentrations 
in relation to age group, dose level, and glucocorticoid treatment at entry (7-<18 
years only), as applicable. 
Pharmacodynamic Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover, as well as exploratory biomarkers of safety and efficacy, including in 
the additional 12 to <18 years age group: suppression of the gonadal axis (LH, 
FSH) and suppression of the thyroid axis (TSH, FT4), will be assessed.  
Standard descriptive statistics will be used to summarize PD biomarkers by dose 
level within age group.  Change from baseline will be presented.  For subjects 7 
to <18 years of age, descriptive statistics will be presented separately for those 
subjects who were on SoC glucocorticoid therapy at the time of assignment to a 
dose group and those subjects who had been off SoC glucocorticoid therapy for 
at least 3 months at the time of assignment to a dose group.   
The changes in serum PD biomarkers will be compared to the data collected in a 
previously conducted vamorolone study VBP15-004. The changes from baseline 
to week 12 in the present study (by dose level and age group) will be compared 
to the changes from baseline to week 12 in the four treatment groups of study 
VBP15-004 (vamorolone 2.0 mg/kg, vamorolone 6.0 mg/kg, placebo and 
prednisone 0.75 mg/kg). Furthermore, the differences between the groups will be 
evaluated with ANCOVA models including baseline value as a covariate and the 
treatment/age group as a fixed factor. Additional analyses will be conducted by 
glucocorticoid use group, when appropriate.  
Clinical Efficacy Analyses: 

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Amendment #3                            
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The exploratory efficacy outcomes are the Bayley-III Gross Motor scale (2 to <4 
years age group) and PUL Test (7 to <18 years age group).  Standard descriptive 
statistics will be used to summarize the clinical efficacy endpoints by dose level 
within age group. Change from baseline will be presented.  Within each age 
group, pairwise comparisons will be made to compare change from baseline for 
the vamorolone 6 mg/kg/day dose level group vs. the vamorolone 2 mg/kg/day 
dose level group.  For subjects 7 to <18 years of age, descriptive statistics will be 
presented separately for those subjects who were on SoC glucocorticoid therapy 
at the time of assignment to a dose group and those subjects who had been off 
SoC glucocorticoid therapy for at least 3 months at the time of assignment. 
Furthermore, the changes from baseline to week 12 will be compared using 
ANCOVA models, including baseline value as a covariate and dose level and 
glucocorticoid use status (when appropriate) and the relevant interaction terms as 
fixed factors. Separate models will be used for each age group. 
Patient-reported Outcome Analyses: 
Patient-reported Outcomes including the PODCI, PARS III, Ease of Study 
Medication Administration Assessment, and the Study Medication Acceptability 
Assessment will be listed and presented using descriptive statistics by age group, 
dose level, and time point.  For subjects 7 to <18 years of age, descriptive 
statistics for change from baseline assessments (PODCI and PARS III) will be 
presented separately for those subjects who were on SoC glucocorticoid therapy 
at the time of participation and those subjects who had been off SoC 
glucocorticoid therapy for at least 3 months at the time of assignment to a dose 
group.  

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11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
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TABLE OF CONTENTS 
SERIOUS ADVERSE EVENT CONTACT INFORMATION .....................................4 
PROTOCOL AMENDMENT TRACKING....................................................................5 
STUDY SYNOPSIS ...........................................................................................................7 
TABLE OF CONTENTS ................................................................................................18 
LIST OF TABLES ...........................................................................................................25 
LIST OF ABBREVIATIONS .........................................................................................26 
1. 
INTRODUCTION...................................................................................................30 
1.1. 
BACKGROUND AND UNMET NEED ......................................................................30 
1.2. 
NONCLINICAL EXPERIENCE ...............................................................................32 
1.3. 
CLINICAL EXPERIENCE ......................................................................................32 
1.4. 
PHARMACOKINETICS OF VAMOROLONE ...........................................................32 
1.5. 
SAFETY AND EFFICACY OF VAMOROLONE IN DMD (STUDY VBP-004) ...........33 
1.6. 
RATIONALE FOR STUDY DESIGN ........................................................................36 
1.7. 
OVERALL BENEFIT/RISK ....................................................................................40 
2. 
STUDY OBJECTIVES AND ENDPOINTS .........................................................41 
2.1. 
STUDY OBJECTIVES ............................................................................................41 
2.1.1. 
Primary Objective ....................................................................................41 
2.1.2. 
Secondary Objectives...............................................................................41 
2.1.3. 
Exploratory Objectives ............................................................................41 
2.2. 
STUDY ENDPOINTS ..............................................................................................42 
2.2.1. 
Safety Endpoints ......................................................................................42 
2.2.2. 
Pharmacokinetic Endpoints ....................................................................43 
2.2.3. 
Exploratory Endpoints ............................................................................44 

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2.2.4. 
Pharmacodynamic Endpoints .................................................................44 
2.2.5. 
Endpoints for Patient-Reported Outcomes ...........................................45 
3. 
STUDY DESIGN .....................................................................................................46 
3.1. 
OVERALL STUDY DESIGN ...................................................................................46 
3.2. 
STUDY SUMMARY ...............................................................................................47 
3.3. 
DOSE GROUP ASSIGNMENT ................................................................................51 
4. 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS .........................53 
4.1. 
SUBJECT ENROLLMENT AND IDENTIFICATION LOG .........................................53 
4.2. 
INCLUSION CRITERIA .........................................................................................53 
4.3. 
EXCLUSION CRITERIA ........................................................................................55 
4.4. 
WITHDRAWAL OF SUBJECTS FROM STUDY........................................................57 
4.5. 
TERMINATION OF STUDY....................................................................................58 
5. 
TREATMENT OF STUDY SUBJECTS ..............................................................60 
5.1. 
STUDY MEDICATION ADMINISTERED ................................................................60 
5.2. 
IDENTITY OF INVESTIGATIONAL PRODUCT .......................................................60 
5.3. 
DOSAGE SCHEDULE AND ADMINISTRATION OF STUDY MEDICATION ..............61 
5.4. 
RATIONALE FOR DOSE SELECTION ....................................................................62 
5.5. 
TREATMENT COMPLIANCE ................................................................................64 
5.6. 
STUDY DRUG DOSE INTERRUPTION OR DISCONTINUATION .............................65 
5.7. 
PRIOR AND CONCOMITANT MEDICATIONS AND THERAPIES ............................65 
5.7.1. 
Prior Therapy ...........................................................................................65 
5.7.2. 
Concomitant Therapies ...........................................................................66 
5.7.3. 
Prohibited Therapies ...............................................................................66 
5.7.4. 
Permitted Therapies ................................................................................68 

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5.7.5. 
Hydrocortisone .........................................................................................68 
5.7.6. 
Vitamin D ..................................................................................................68 
5.8. 
STUDY MEDICATION MANAGEMENT .................................................................68 
5.8.1. 
Packaging and Labeling of Study Medication ......................................68 
5.8.2. 
Storage of Study Medication ...................................................................69 
5.8.3. 
Study Medication Shipping and Handling ............................................69 
5.8.4. 
Study Medication Accountability ...........................................................71 
5.9. 
PROCEDURES FOR ASSIGNING SUBJECT IDENTIFICATION NUMBERS ...............71 
6. 
STUDY SCHEDULE ..............................................................................................73 
6.1. 
TIME AND EVENTS SCHEDULE ...........................................................................73 
6.2. 
INFORMED CONSENT AND ASSENT PROCEDURES..............................................78 
6.2.1. 
HIPAA and Protected Health Information ...........................................79 
6.3. 
VISIT SCHEDULE AND PROCEDURES ..................................................................79 
6.3.1. 
Screening Period (Day -33 to -2) .............................................................80 
6.3.2. 
Baseline Period (Day -1) Visit .................................................................82 
6.3.3. 
Treatment Period Day 1 Visit .................................................................82 
6.3.4. 
Treatment Period (Weeks 1-12) ..............................................................84 
6.3.5. 
Dose-tapering Period (Weeks 13-16) ......................................................86 
6.4. 
SUBJECT DISCONTINUATION ..............................................................................88 
6.5. 
SUBJECT AND STUDY COMPLETION ...................................................................89 
7. 
STUDY ASSESSMENTS AND MEASUREMENTS ..........................................90 
7.1. 
DEMOGRAPHIC ASSESSMENTS ...........................................................................90 
7.2. 
SAFETY AND TOLERABILITY ASSESSMENTS ......................................................90 
7.2.1. 
Medical History ........................................................................................90 

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7.2.2. 
Physical Examination, Cushingoid Features, Ambulatory status, 
Weight, and Height ..................................................................................90 
7.2.3. 
Vital Signs .................................................................................................91 
7.2.4. 
Clinical Laboratory Tests........................................................................91 
7.2.5. 
Chicken Pox Immunity ............................................................................94 
7.2.6. 
Pharmacodynamic Biomarker Panel .....................................................95 
7.2.7. 
Pharmacokinetic Assessment ..................................................................96 
7.2.8. 
Total Blood Volume Required ................................................................97 
7.2.9. 
12-Lead ECG ............................................................................................98 
7.2.10. 
Eye Examination ......................................................................................99 
7.3. 
ASSESSMENT OF MUSCLE FUNCTION .................................................................99 
7.3.1. 
Bayley Scales of Infant and Toddler Development-III (Bayley-III) 
Gross Motor Scale ....................................................................................99 
7.3.2. 
Performance of Upper Limb (PUL) Test .............................................100 
7.4. 
PATIENT-REPORTED OUTCOME MEASURES ...................................................100 
7.4.1. 
Pediatric Outcomes Data Collection Instrument (PODCI) ...............100 
7.4.2. 
Behavioral Assessment ..........................................................................100 
7.4.3. 
Ease of Study Medication Administration Assessment ......................101 
7.4.4. 
Study Medication Acceptability Assessment .......................................101 
7.5. 
SUBJECT DIARY ................................................................................................101 
7.6. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS........................................101 
7.6.1. 
Intensity ..................................................................................................102 
7.6.2. 
Relationship ............................................................................................103 
7.6.3. 
Clinical Laboratory Test Abnormalities ..............................................104 

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7.6.4. 
Follow-Up of Adverse Events ................................................................105 
7.6.5. 
Dosing Error ...........................................................................................106 
7.6.6. 
Serious Adverse Events .........................................................................106 
8. 
STUDY COMMITTEES ......................................................................................110 
8.1. 
DATA AND SAFETY MONITORING BOARD .......................................................110 
9. 
DATA COLLECTION .........................................................................................111 
9.1. 
SOURCE DOCUMENTS .......................................................................................111 
9.2. 
ELECTRONIC CASE REPORT FORM COMPLETION ..........................................111 
9.3. 
DATA PROCESSING ...........................................................................................112 
9.4. 
SUBJECT DIARIES .............................................................................................112 
10. STATISTICAL METHODS AND PLANNED ANALYSES ............................113 
10.1. SAMPLE SIZE DETERMINATION .......................................................................113 
10.2. STATISTICAL AND ANALYTICAL PLAN (SAP) ..................................................113 
10.2.1. 
Deviations from the Statistical Analysis Plan ......................................113 
10.3. ANALYSIS POPULATIONS ..................................................................................114 
10.3.1. 
Safety Population ...................................................................................114 
10.3.2. 
Modified Intent-to-Treat (mITT) Population .....................................114 
10.3.3. 
Pharmacokinetic (PK) Population........................................................114 
10.4. MEASURES TAKEN TO AVOID/MINIMIZE BIAS................................................114 
10.5. INTERIM ANALYSIS ...........................................................................................114 
10.6. MISSING, UNUSED, AND SPURIOUS DATA ........................................................114 
10.7. STATISTICAL ANALYSIS ...................................................................................115 
10.7.1. 
General Considerations .........................................................................115 
10.7.2. 
Subject Disposition, Demographics, and Baseline Characteristics ...115 

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10.7.3. 
Safety and Tolerability Analyses ..........................................................115 
10.7.4. 
Pharmacokinetic Analyses ....................................................................116 
10.7.5. 
Pharmacodynamic Analyses .................................................................117 
10.7.6. 
Clinical Efficacy Analyses .....................................................................118 
10.7.7. 
Patient-Reported Outcome Analyses ...................................................118 
10.7.8. 
Concurrent Medications ........................................................................119 
11. STUDY MANAGEMENT AND ETHICAL AND REGULATORY 
REQUIREMENTS................................................................................................120 
11.1. REGULATORY APPROVAL AND GOOD CLINICAL PRACTICE...........................120 
11.2. INVESTIGATOR RESPONSIBILITIES...................................................................120 
11.2.1. 
Subject Information and Informed Consent .......................................120 
11.2.2. 
Institutional Review Board/Independent Ethics Committee 
Approval and Other Institutional Requirements................................121 
11.2.3. 
Study Documentation ............................................................................122 
11.2.4. 
Delegation of Investigator Responsibilities ..........................................124 
11.3. PROTOCOL DEVIATIONS ...................................................................................124 
11.3.1. 
Protocol Deviation Definitions ..............................................................124 
11.3.2. 
Reporting Important Protocol Deviations ...........................................125 
11.4. STUDY RECORDS RETENTION AND DIRECT ACCESS TO SOURCE 
DOCUMENTS .....................................................................................................125 
11.5. STUDY MONITORING ........................................................................................126 
11.6. QUALITY ASSURANCE ......................................................................................127 
11.7. STUDY TERMINATION AND SITE CLOSURE ......................................................128 
11.8. SITE TERMINATION ..........................................................................................128 

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11.9. DISCONTINUATION OF STUDY ..........................................................................129 
12. DISCLOSURE OF DATA ....................................................................................130 
12.1. CONFIDENTIALITY ............................................................................................130 
12.2. PUBLICATION ....................................................................................................131 
13. INVESTIGATOR PROTOCOL AGREEMENT ..............................................133 
14. REFERENCES ......................................................................................................134 
15. APPENDICES .......................................................................................................137 
15.1. VAMOROLONE DOSE CALCULATION WORKSHEET AND BULK DISPENSING 
GUIDE ................................................................................................................137 
15.1.1. 
Dose Calculation Worksheet .................................................................137 
15.1.2. 
Vamorolone 4.0% Suspension Dispensing Guide ...............................137 
15.2. PROTOCOL AMENDMENT #1 COMPLETE LIST OF CHANGES ..........................139 
15.3. PROTOCOL AMENDMENT #2 COMPLETE LIST OF CHANGES ..........................163 
 

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LIST OF TABLES 
 
Table 1. 
Study Assignment Schedule .................................................................................................. 37 
Table 2. 
Schedule of Study Activities .................................................................................................. 74 
Table 3. 
Study Medication Dose Tapering ........................................................................................... 87 
Table 4. 
Hematology, Chemistry, and Lipids Clinical Laboratory Tests ................................................ 93 
Table 5. 
Urinalysis Clinical Laboratory Tests ....................................................................................... 93 
Table 6. 
Pharmacodynamic Biomarkers – Exploratory Safety Outcomes ............................................ 96 
Table 7. 
Blood Sample Number and Volume by Study Visit ................................................................ 98 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition/Term 
%CV 
percent coefficient of variation 
ACTH 
adrenocorticotropic hormone 
ADL 
activities of daily living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0-24hr 
area under the concentration-time curve from time 0 to 24 hours 
AUC(0-t) 
area under the concentration-time curve from time 0 to time t 
AUC(inf) 
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 
Bayley-III 
Bayley Scales of Infant and Toddler Development-III 
BMI 
body mass index 
BUN 
blood urea nitrogen 
C 
Celsius 
CFR 
CIOMS 
Code of Federal Regulations 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CL 
clearance 
ConA 
Concanavalin A 
cm 
centimeter 
Cmax 
maximum observed plasma concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTM 
Clinical Trial Material 
CTMS 
Clinical Trial Management Software 
CTX 
C-terminal peptide fragment of collagen 1 
CYP 
DILI 
cytochrome P450 
drug-induced liver injury 
dL 
deciliter 
DMD 
Duchenne muscular dystrophy 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 

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Abbreviation 
Definition/Term 
F% 
percent bioavailability 
FDA 
Food and Drug Administration 
GALT 
gut-associated lymphoid tissue 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GLDH 
glutamate dehydrogenase 
GLP 
Good Laboratory Practice 
HbA1c 
hemoglobin A1c 
HDL 
high density lipoprotein 
HEENT 
head, eyes, ears, nose and throat 
HIPAA 
Health Insurance Portability and Accountability Act 
hr 
hour 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
identification 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IXRS 
Interactive Voice/Web Response System 
kg 
kilogram 
L 
liter 
LLC 
Limited Liability Company 
LDH 
lactate dehydrogenase 
LDL 
low density lipoprotein 
LS 
least squares 
μg 
microgram 
m 
meter 
m2 
square meter 
MAD 
multiple ascending dose (study) 
MD 
Medical Doctor (physician) 
Mdx 
mouse model lacking dystrophin 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
min 
minute 
mITT 
modified Intent-to-Treat 
mL 
milliliter 
MTD 
maximum tolerated dose 
N, No. 
number 
NADPH 
nicotinamide adenine dinucleotide phosphate 

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Abbreviation 
Definition/Term 
NCA 
noncompartmental analytical (methods) 
NF-κB 
nuclear factor kappa-light-chain-enhancer of activated B cells 
ng 
nanogram 
nM 
nanomolar 
nmol 
nanomole 
NOAEL 
no observed adverse effect level 
OECD 
Organisation for Economic Cooperation and Development 
OTC 
over-the-counter (non-prescription medication) 
oz 
ounce 
P1NP 
aminoterminal propeptide of type I collagen 
PARS III 
Personal Adjustment and Role Skills Scale III 
PBL 
peripheral blood leukocytes 
PD 
pharmacodynamics 
PHI 
Protected Health Information 
PK 
pharmacokinetics 
PODCI 
Pediatric Outcomes Data Collection Instrument 
PR [PQ] 
time from onset of P wave to start of the QRS complex 
PUL 
Performance of Upper Limb (Test) 
QD 
once daily (dosing) 
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 time between the start of the Q wave and end of 
the T wave 
QTc 
corrected QT interval 
RBC 
ROS 
Red Blood Cell 
route of synthesis 
RR 
in electrocardiography, the interval between successive Rs (peaks of 
QRS complexes) 
SAD 
single ascending dose (study) 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOC 
system organ class 
SOP 
standard operating procedures 
SSC 
Study Steering Committee 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 

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Abbreviation 
Definition/Term 
Tmax 
time to maximum observed plasma concentration 
TRiNDS 
Therapeutic Research in Neuromuscular Disorders Solutions 
US 
United States 
vs. 
versus 
Vss 
volume of distribution at steady state 
WBC 
White Blood Cell 
WHO 
World Health Organization 
wt 
weight 
 

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1. 
INTRODUCTION 
1.1. 
Background and Unmet Need 
DMD is the most common childhood muscular dystrophy with a birth incidence 
worldwide of 1 in 3,600 to 9,300 males [Mah et al, 2014]. Clinical characteristics of 
DMD are proximal muscle weakness presenting in childhood and progressive 
involvement of most muscle groups, leading to loss of ambulation late in the first decade 
or early in the second decade of life. Weakness progresses, with the patient requiring 
assistance with the activities of daily living by the late teens or in their early twenties. 
Patients with DMD often succumb from respiratory failure and/or cardiac failure.  
DMD is an X-linked recessive disorder caused by mutations in the DMD gene [Koenig 
1987] which codes for the dystrophin protein that provides structural stability to the 
dystrophin-associated glycoprotein complex on muscle cell membranes [Hoffman et al, 
1987]. The lack of dystrophin reduces plasma membrane stability, resulting in membrane 
fragility and necrosis [Evans et al, 2009].  
Upregulated inflammatory gene expression and activated immune cell infiltrates are 
present during early disease stages and play a significant role in muscle wasting [Chen et 
al, 2005]. The transcription factor NF-κB has been shown to regulate the expression of 
numerous inflammatory genes in immune cells and muscle fibers [Pahl, 1999; Dogra et 
al, 2006; Acharyya et al, 2007; Kumar et al, 2003] and the infiltration and activation of 
these cells can trigger muscle fiber death [Acharyya et al, 2007].  
GR agonists, such as prednisone and deflazacort [Malik et al, 2012] are currently the 
cornerstone for the treatment of patients with DMD according to American Academy of 
Neurology practice guidelines [Gloss et al, 2016] and the DMD Care Considerations 
Working Group [Birnkrant et al, 2018]. The benefits of long-term glucocorticoid therapy 
have been shown to include loss of ambulation at a later age, preserved upper limb and 
respiratory function, and avoidance of scoliosis surgery [Birnkrant et al, 2018].  
The adverse effects of glucocorticoids include weight gain, cushingoid appearance, 
growth delay, behavior changes, an increased frequency of vertebral fractures, skin 
fragility, cataract, increased intra ocular pressure, adrenal suppression, insulin resistance 

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[Kauh et al, 2012] and muscle atrophy [Schakman et al, 2013]. These adverse drug 
reactions (ADRs) negatively impact quality of life and cause considerable variation in 
clinical practice including suboptimal dosing [Griggs et al, 2013; Bello et al, 2015].  
The significant adverse effects of glucocorticoids on growth also prevent their routine 
administration in infants or toddlers, despite evidence that better outcomes are achieved 
with earlier administration [Merlini et al, 2012; Pane et al, 2014; Ciafaloni et al, 2016; 
Connolly et al, 2019; McMillan 2019; Buckon et al, 2022].  
There is therefore an ongoing need to develop glucocorticoids with a better safety profile. 
Rationale to develop vamorolone for DMD  
Preclinical and clinical studies have shown that vamorolone addresses the anti- 
inflammatory activity of the GR and avoids some of its unwanted effects such as growth 
stunting, inhibition of bone metabolism, and induction of neutrophilia.  
The anti-mineralocorticoid activity of vamorolone, as shown in the preclinical studies 
may be beneficial since the renin-angiotensin-aldosterone axis is thought to be involved 
in the pathogenesis of skeletal muscle fibrosis and cardiomyopathy in DMD [Rodriguez-
Gonzalez et al, 2021; Howard et al, 2022].  
In addition, the lack of activation/inactivation of vamorolone by 11-β-HSD 1 and 2 may 
be an advantage since the pharmacological activity of prednisone, including some of its 
adverse effects such as osteoporosis, is linked to its local activation to prednisolone by 
11- β-HSD 1 [Fenton et al, 2019; Morgan et al, 2014; Fenton et al, 2021; Webster et al, 
2021; Cooper et al, 2003].  
Lastly, the observed effect of cell membrane repair after injury in mice may be 
particularly relevant for dystrophin-deficient cells in DMD where plasma membranes are 
inherently unstable.  
Based on this differentiated profile, vamorolone has the potential to combine the known 
efficacy of glucocorticoids in DMD with a better safety profile.   
 

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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. Refer to the current IB for updated 
information on the nonclinical experience of vamorolone.  
1.3. 
Clinical Experience 
Clinical experience with vamorolone is comprised of a completed Phase I clinical trial of 
vamorolone in healthy adult volunteers (VBP15-001), completed Phase IIa (VBP15-002) 
and Phase II extension (VBP15-003) trials in DMD boys, completed Phase II long-term 
extension (VBP15-LTE) trial in DMD boys, and a completed Phase IIb active- and 
placebo-controlled trial in DMD boys (VBP15-004).  Vamorolone is extensively 
metabolized in the liver hence the impact of an impaired hepatic function on vamorolone 
PK was assessed in a clinical study in adult volunteers with moderate impaired hepatic 
function [VBP15-HI].  [VBP15-DDI ] study  investigated  the  effect  of  itraconazole  on  
the  PK  of  on a single dose of vamorolone in healthy subjects. Furthermore, two relative 
bioavailability (BA) and food effect (FE) studies have been conducted (VBP15-
PKFORM and VBP15-PKFORM-002) comparing the formulation used in clinical studies 
(ROS1) with the to-be-marketed formulation (ROS2).  
Refer to the current IB version for updated and detailed information on the development 
program for vamorolone.  
1.4. 
Pharmacokinetics of Vamorolone 
The PK of vamorolone in subjects with DMD aged 4 to 7 years was thoroughly evaluated 
with intense PK sampling on Days 1 and 14 of daily vamorolone administration in Study 
VBK15-002.  Vamorolone peak plasma concentrations occurred on average 2 to 4 hours 
after dosing, exposure increased linearly with dose and the exposure after 
6.0 mg/kg/day in terms of mean (SD) Cmax and AUC0-inf was 970 (270) ng/mL and 
3606 (897) ng.hr/mL, respectively on Day 14).  The mean (SD) t½ of vamorolone at 

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6.0 mg/kg/day was 1.4 (0.35) hours and no accumulation is observed with daily 
administration. 
The Population PK (PPK) evaluation based on PK data from studies VBP15-002 and 
VBP15-004 estimated the CL/F and V/F values for a typical DMD patient weighing 20 
kg and taking vamorolone with a meal as 58 L/hr and 162 L, respectively The PPK 
estimate vamorolone Tmax is 2.4 hours, the estimated elimination half-life in DMD boys 
is 1.9 hours and the calculated exposure at steady state after 6.0 mg/kg/day in terms of 
Cmax and AUC0-inf was 555 ng/mL and 2944 ng.hr/mL, respectively, in a typical DMD 
patient weighing 20 kg and taking vamorolone with a meal. 
The results of the two bioavailability/food effect studies (VBP15-PK-FORM and 
VBP15-PK-FORM-002) support the change from the Clinical Formulation (ROS1) to the 
To-be-marketed Formulation (ROS2). The To-be marketed Formulation (ROS2) 
demonstrates a lower food effect than the Clinical Formulation (ROS1) and offers more 
reliable dosing (i.e., more consistent exposure) when taken with different types of food.  
Hepatic impairment increases the exposure to vamorolone. Subjects with moderate HI 
had 1.7 and 2.6-fold higher Cmax and AUC0inf values compared to age, weight and sex 
matched healthy adults  
The PK evaluation based on all 18 subjects showed no relevant increase in peak 
concentrations of vamorolone in the presence of the potent CYP3A4 inhibitor 
itraconazole, but AUC0-inf  increased  by  33.7%.  Median  Tmax  of  vamorolone  was  
2 hours  when  administered alone and was delayed when combined with itraconazole (4 
hours). Thus, itraconazole has a weak effect on vamorolone PK. 
Refer to the current IB version for full and updated clinical pharmacology information. 
1.5. 
Safety and Efficacy of Vamorolone in DMD (Study VBP-004) 
The results of study VBP15-004, a randomized, double-blind, placebo controlled and 
prednisone referenced study showed that vamorolone produced clinically meaningful, 
statistically significant, and robust improvements in multiple measurements of lower limb 
motor function compared to placebo after 24 weeks of treatment. The improvements in 

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motor function with vamorolone were similar to those seen with prednisone, a standard of 
care for children with DMD. The positive effects achieved at 24 weeks with vamorolone 
6 mg/kg remained stable over the course of the second period of the pivotal trial up to 48 
weeks, both for patients who remained on vamorolone 6 mg/kg in both periods and for 
those who switched from prednisone 0.75 mg/kg to vamorolone 6 mg/kg. Although the 
magnitude of effects on motor function in vamorolone 2 mg/kg was less well maintained 
over time, an improvement compared to baseline was still observed after 12 months. 
In study VBP15-004, a higher proportion of subjects presented with a least one TEAE in 
the vamorolone 2 and 6 mg/kg groups (83.3% and 89.3%, respectively) compared to 
placebo (79.3%) but in line with the prednisone 0.75 mg/kg group (83.9%). Clinically-
relevant TEAEs, pre-defined as moderate to severe events, SAEs, or events leading to 
discontinuation, were reported at similar rates in the placebo (31.0%) and vamorolone 2 
mg/kg groups (26.7%), less in the vamorolone 6 mg/kg group (14.3%), and more 
frequent in the prednisone 0.75 mg/kg group (41.9%). These results indicate that the 
increased proportion of subjects presenting with at least one TEAE in both of the 
vamorolone groups compared to placebo was driven by an excess in mild TEAEs, while 
prednisone was also associated with an increase in moderate to severe events.   
Adverse Events of Special Interest, pre-defined as groupings of events typically 
associated with glucocorticosteroid therapy, were reported in a similar percentage of 
subjects in the placebo (69.0%) and vamorolone 2 mg/kg (66.7%) groups and higher 
percentages in the prednisone 0.75 mg/kg (77.4%) and vamorolone 6 mg/kg (78.6%) 
groups.  
The safety profile of vamorolone shares some risks with those described with 
glucocorticoids, such as: 
x Vamorolone causes dose-dependent adrenal suppression. The level of adrenal 
suppression was slightly larger in vamorolone 6 mg/kg than prednisone 0.75 
mg/kg based on mean morning cortisol values, while the vamorolone 2 mg/kg had 
a partial effect.   

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x Cushingoid features were frequently reported dose-dependent AEs with 
vamorolone. The incidence of cushingoid features were similar in vamorolone 6 
mg/kg and prednisone 0.75 mg/kg. Most of the events were reported as non-
clinically significant and did not lead to discontinuation of vamorolone.   
x Vamorolone 6 mg/kg was associated with an increase in BMI compared to 
placebo and comparable to the effect seen in prednisone 0.75 mg/kg. Vamorolone 
2 mg/kg showed a less pronounced effect of limited clinical relevance.  
x Vamorolone 6 mg/kg was associated with an increased risk for behavioural 
problems, mainly mild irritability, which were more frequently reported in the 
first 6 months of treatment.   
x Gastrointestinal symptoms were reported at similar frequency than placebo over 
the first 6 months of treatment but showed evidence for dose-dependency over the 
long-term treatment suggestive of a drug effect.    
While the safety profile of vamorolone shares some risks with those described with 
glucocorticoids, it shows clinically relevant differences for a clinically improved safety 
profile in long-term therapy:  
x Absence of a deleterious effect on biomarkers of bone metabolism  
x Normal growth with any dose of vamorolone, supported by the absence of a 
change in height z-scores similar to placebo at 6 months, 12 months and in the 
long term in study VBP15-LTE, while evidence of growth stunting was already 
seen at Month 6 for the prednisone group. 
x A reduced frequency and severity of behavior related events on 6 mg/kg 
vamorolone compared with prednisone, while 2 mg/kg vamorolone was similar to 
placebo. 
In addition, the findings of the vamorolone development programs suggests the potential 
for other differential effect in the long-term safety profile of vamorolone, such as: 

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x Absence of a clinically relevant effect on glucose metabolism in study VBP15-
004 and over up to 30 months of treatment in study VBP15-002/002/LTE 
x Absence of an effect on neutrophil counts while neutrophilia was observed early 
after starting treatment with prednisone. 
x Absence of cases of cataracts or increase in intraocular pressure in studies 
VBP15-004 and VBP15-002/003/LTE  
Additional long-term data would be required to further characterize the risks. 
These data support a positive benefit-risk profile for vamorolone at the 2 mg/kg and 6 
mg/kg doses. The efficacy at the vamorolone 6 mg/kg dose is similar to current standard 
of care, prednisone, with an improved safety and tolerability profile compared to 
prednisone. The vamorolone 2 mg/kg shows robust efficacy compared to placebo at 24 
weeks and a further improved safety and tolerability profile compared to vamorolone 6 
mg/kg and prednisone 0.75 mg/kg.  
Refer to the current IB version for the most updated clinical information.  
1.6. 
Rationale for Study Design 
The current Phase II study is designed to confirm the safe and tolerable dose(s) of 
vamorolone to be used to treat DMD in boys aged 2 to <4 years and 7 to <18 years, based 
upon safety and PK data, and to perform an exploratory evaluation of PD, clinical 
efficacy, behavior and neuropsychology, and physical functioning over a treatment period 
of 12 weeks.  Steroid-naïve subjects in the 2 to <4 years age group will be recruited for 
study, dictated by 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.  Enrollment of boys in the 7 to <18 years age group will be stratified to 
accommodate both glucocorticoid-treated and glucocorticoid-untreated subjects at time of 
study entry, to reflect real-world clinical experience with glucocorticoid treatment for 
DMD in older boys; analyses will be conducted separately for subjects in each 
glucocorticoid treatment group. A group of 10 subjects is added to ensure a sufficient 
number of glucocorticoid-treated subjects 12 to <18 years of age are exposed to the 

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higher dose (6 mg/kg). This change is introduced through protocol amendment #2 
because the 7 to <18 years of age group is recruiting a very limited number of these older 
subjects. This imbalanced recruitment could potentially prevent objectives of the study to 
be met by not sufficiently exploring the 12 to <18 years age range. 
The vamorolone dose levels of 2.0 mg/kg/day and 6.0 mg/kg/day chosen for study have 
been shown to be safe and well-tolerated, and associated with improvements in muscle 
and strength assessments, in previous and ongoing vamorolone Phase II studies in boys 
4 to <7 years of age.  As a new route of synthesis of vamorolone, ROS2, will be used, 
boys will enroll into the 2.0 mg/kg/day group first, and drug exposure compared to 
previous ROS1 experience prior to enrolling into the higher 6.0 mg/kg/day dose group. 
Based on pharmacokinetics of vamorolone, the daily dose will be capped for the patients 
weighing 50 kg and above at 300mg in the 6mg/kg/day dose groups and 100mg in the 
2mg/kg/day dose groups. 
Subjects who meet all eligibility criteria in this study (VBP15-006) will be assigned to 
one of seven treatment groups as shown in Table 1. Groups 1, 3, and 4 will be fully 
enrolled at 2.0 mg/kg/day prior to assignment of subsequent participants to Groups 2, 5, 6 
and 7 at 6.0 mg/kg/day. 
Table 1. 
Study Assignment Schedule 
Group 
Planned 
Number of 
Subjects 
Glucocorticoid 
Status 
Ages 2 to <4 Years 
Ages 7 to <18 Years  
1 
10 
Naïve* 
Vamorolone, 2.0 mg/kg/day 
 
2 
10 
Naïve* 
Vamorolone, 6.0 mg/kg/day 
 
3 
6 
Untreated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
4 
6 
Treated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
5 
6 
Untreated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
6 
6 
Treated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
7 
10 
Treated at entry 
 
Vamorolone, 6.0 
mg/kg/day/  
*Naïve is defined as having had no prior glucocorticoid treatment for DMD, and past transient use of oral 
glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last 
use at least 3 months prior to enrollment, to be considered for enrollment on a case-by-case basis. 

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Group 1 (age 2 to <4 years, vamorolone 2.0 mg/kg/day), Group 3 (age 7 to <18 years 
untreated at entry, vamorolone 2.0 mg/kg/day), and Group 4 (age 7 to <18 years treated at 
entry, vamorolone 2.0 mg/kg/day) will be fully enrolled prior to Groups 2, 5, 6 and 7 
(6.0 mg/kg/day).   
Evaluation of the two dose levels of vamorolone during the 12-week Treatment Period in 
this study will allow comparison of change from baseline in safety parameters, muscle 
strength and functional efficacy parameters, and PD biomarker levels over 12 weeks of 
treatment within each age group.   
Key safety parameters in conjunction with PK data will be evaluated during the course of 
the study to assess vamorolone safety and tolerability.   
To evaluate clinical efficacy, effect of vamorolone 2.0 mg/kg/day and 6.0 mg/kg/day on 
muscle strength will be assessed using the Bayley-III Gross Motor scale (2 to <4 years 
age group) and the Performance of Upper Limb (PUL) Test (7 to <18 years age group).  
These functional assessments were chosen as accurate reflections of muscle strength for 
subjects with DMD within each of the two age groups studied [Connolly et al. 2014]; 
Pane at al. 2014].  
Moreover, behavior and neuropsychology, physical functioning, and sleep-wake activity 
will be measured as exploratory outcomes using the Personal Adjustment and Role Skills 
Scale III (PARS III), and Pediatric Outcomes Data Collection Instrument (PODCI).  
Acceptability of the vamorolone suspension will be assessed using the parent-reported 
Ease of Study Medication Administration Assessment (ages 2 to <4 years) and the 
subject-reported Study Medication Acceptability Assessment (ages 7 to <18 years).   
Pharmacodynamic safety biomarker findings in DMD patients receiving vamorolone 
2.0 mg/kg/day or 6.0 mg/kg/day over 12 weeks will be compared within each age group.  
Serum PD biomarkers bridged to later clinical safety concerns will be assessed over time 
as exploratory safety measures.  These PD biomarkers include: 
1. Adrenal suppression.  Pharmacological doses of glucocorticoids cause 
suppression of the hypothalamo-pituitary-adrenal axis, leading to low 
concentration of endogenous cortisol and other steroidal hormones in serum.  

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Adrenal suppression is directly associated with risk of adrenal crisis,.  
Measurement of morning cortisol concentrations, 24 hr after the last dose,  will 
reflect the degree of adrenal suppression.  Plasma cortisol secretion typically 
follows a circadian pattern with the highest concentrations early in the morning; a 
morning serum cortisol concentration less than 3.6 μg/dL (or 100 nM) is highly 
suggestive of adrenal suppression.   
2. Bone turnover.  Pharmacological doses of glucocorticoids suppress  bone 
formation and bone resorption, leading to later osteopenia and bone fragility [van 
Staa et al. 2000]. Bone fragility is a significant adverse effect of chronic 
pharmacologic glucocorticoids in DMD as this can lead to fracture, especially 
vertebral fractures, which increases the likelihood of premature loss of 
ambulation.  Serum biomarkers that have been bridged to later clinical outcomes 
of osteopenia in adults are osteocalcin (bone formation; glucocorticoids decrease 
serum levels), aminoterminal propeptide of type I collagen (P1NP) (bone 
formation; glucocorticoids decrease serum levels), and CTX (bone resorption; 
glucocorticoids increase serum levels in adults 
3. Insulin resistance.  Insulin resistance has been bridged to later clinical outcomes, 
including heart disease, type 2 diabetes, and vascular disease.  Serum biomarkers 
that are accepted as measures of insulin resistance are increased serum glucose 
and insulin.  This can be measured after acute (hours after first dose) or chronic 
(after weeks or months of dosing) glucocorticoid treatment. 
Exploratory safety outcomes will be assessed  by  additional serum safety biomarkers that 
have been defined in glucocorticoid-treated DMD and inflammatory bowel disease 
patients.  Additional exploratory measures of efficacy include PD biomarkers that have 
previously been shown to be glucocorticoid-responsive in DMD boys, pediatric 
inflammatory bowel disease, adult vasculitis, and pediatric myositis.  
This trial will be conducted in compliance with this protocol, and in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki, and that are 
consistent with Good Clinical Practice (GCP) and the applicable Health Canada 

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regulatory requirements , and the issued FDA guidance on developing drugs for treatment 
for DMD and related dystrophinopathies [FDA, 2015].  
1.7. 
Overall Benefit/Risk 
Vamorolone has shown positive benefit-risk profile for both doses. The dose of 2mg/kg 
shows an even more favorable safety and tolerability profile as most of the vamorolone-
related risks were dose-dependent, still with evidence of efficacy, thus providing an 
alternative dose with a positive benefit-risk profile that could be considered for patients 
having tolerability concerns. At 6mg/kg dose , the efficacy is similar  to  current  standard  
of  care,  prednisone,  with an improved safety and tolerability profile supporting its use 
as the recommended starting dose for the long-term treatment of DMD. Please refer to 
the current Investigator Brochure for more information.  
 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
The primary objective of this study is: 
To evaluate the safety and tolerability of vamorolone administered orally at daily doses 
of 2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period in boys ages 2 to <4 and 7 
to <18 years with DMD. 
2.1.2. 
Secondary Objectives 
The secondary objectives of this study are: 
1. To evaluate the pharmacokinetics of vamorolone administered orally in boys ages 
2 to <4 and 7 to <18 years with DMD; 
2. To confirm the vamorolone exposure in boys ages 2 to <4 and 7 to18 years with 
DMD at 2.0 and 6.0 mg/kg and to adjust the doses if appropriate to achieve 
similar vamorolone AUCs across the entire pediatric age range. 
2.1.3. 
Exploratory Objectives 
The exploratory objectives of this study are:  
1. To compare the efficacy, as measured by the effect on muscle function, of 
vamorolone administered orally at daily doses of 2.0 mg/kg versus 6.0 mg/kg over 
a 3-month treatment period in boys ages 2 to <4 and 7 to <18 years with DMD; 
2. To evaluate the effect of vamorolone administered orally at daily doses of 
2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period on behavior and 
neuropsychology in boys ages 2 to <4 and 7 to <18 years with DMD;  
3. To evaluate the effect of vamorolone administered orally at daily doses of 
2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period on physical functioning 
in boys ages 2 to <4 and 7 to <18 years with DMD; 

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4. To evaluate the ease of administration of vamorolone in boys ages 2 to <4 years 
with DMD and study medication acceptability of vamorolone in boys ages 7 to 
<18 years with DMD at daily oral doses of 2.0 mg/kg and 6.0 mg/kg; 
5. To investigate the effects of vamorolone administered orally at daily doses of 
2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period on pharmacodynamic 
biomarkers of safety and efficacy in boys ages 2 to <4 and 7 to <18 years with 
DMD. 
2.2. 
Study Endpoints 
2.2.1. 
Safety Endpoints 
For each vamorolone dose level and age group, the following endpoints will be 
evaluated.  Additionally, for selected endpoints, subjects within the 7 to <18 years age 
group who were on glucocorticoid therapy at the time of assignment to a dose group may 
be evaluated separately from those who were off glucocorticoid therapy for at least 3 
months prior to assignment to a dose group: 
1. BMI z-score: Change from baseline to Week 12; 
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 Section 7.6);  
3. Vital signs (sitting blood pressure, heart rate, respiratory rate, and body 
temperature): Change from baseline to each of the scheduled on-treatment and 
post-treatment assessment time points;   
4. Body weight and height: Change from baseline to each of the scheduled on--
treatment and post-treatment assessment time points; 
5. Cushingoid features: Change from baseline to each of the scheduled on-treatment 
and post-treatment assessment time points (changes from baseline will be 
recorded as AEs); 

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6. Clinical laboratory values: Change from baseline to each of the scheduled on--
treatment and post-treatment assessment time points in: 
x Hematology and clinical chemistry 
x Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], 
high density lipoprotein [HDL]) 
x Vitamin D level 
x Urinalysis; 
7. 12-lead ECG: Change from baseline to Week 12; 
8. Eye examination for detection of clinically significant abnormalities (cataracts 
and/or glaucoma): Change from baseline to Week 12. 
Data for the following additional safety outcome will be listed only: 
9. Physical examination findings at each of the pretreatment, on-treatment, and 
post-treatment assessment time points.  
2.2.2. 
Pharmacokinetic Endpoints 
Blood will be collected for vamorolone population PK analysis on Day 1 and Week 2  
visits 
x For ages 2 to <4 years, blood sampling is within 30 minutes prior to and 1-, 2-, 
and 6-hours following the first dose of study medication at the Day 1 Visit, and 
within 30 minutes prior to and 1-, 2- and 6- hours following the daily dose of 
study medication at the Week 2 Visit.   
x For ages 7 to <18 years, blood sampling is within 30 minutes prior to and 1-, 2-, 
4-, 6- and 8-hours following the first dose of study medication at the Day 1 Visit, 
and within 30 minutes prior to and 1-, 2-, 4-, 6- and 8-hours following the first 
dose of study medication at the Week 2 Visit. 

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2.2.3. 
Exploratory Endpoints 
For each vamorolone dose level and age group, the following endpoints will be 
evaluated.  Additionally, for selected endpoints, subjects within the 7 to <18 years age 
group who were on glucocorticoid therapy at the time of assignment to a dose group may 
be evaluated separately from those who were off glucocorticoid therapy for at least 3 
months prior to assignment to a dose group and also between subjects <12 years and 
subjects ≥ 12 years: 
1. Clinical efficacy assessments: Change from baseline to Week 12 in the Bayley-III 
Gross Motor scale (ages 2 to <4 years) and PUL Test (ages 7 to <18 years); 
2. Behavioral changes (PARS III): Change from baseline to Week 12; 
3. Physical functioning (PODCI): Change from baseline to Week 12; 
4. Ease of study medication administration (ages 2 to <4 years) and study 
medication acceptability (ages 7 to <18 years) assessed at each of the scheduled 
study assessment time points 
2.2.4. 
Pharmacodynamic Endpoints 
For each vamorolone dose level and age group, the following pharmacodynamic 
biomarkers reflective of safety concerns of glucocorticoids will be evaluated.  
Additionally, subjects within the 7 to <18 years age group who were on glucocorticoid 
therapy at the time of assignment to a dose group may be evaluated separately from those 
who were off glucocorticoid therapy for at least 3 months prior to assignment: 
1. Adrenal suppression. First-in-morning serum cortisol levels will be measured 
24 hours after the last dose of vamorolone.  Cortisol measures falling below 
2.4 μg/dL (66nM) for boys below 12 years  or 3.6 μg/dL (100 nM) for boys 
12 years or older will be considered to be indicative of adrenal suppression;   
2. Bone turnover.  Measures of serum osteocalcin and serum P1NP are reflective of 
bone formation, and measures of serum CTX are reflective of bone resorption.  
Serum osteocalcin, serum CTX, and serum P1NP will be measured; 

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3. Insulin resistance.  Glucocorticoids cause both acute and chronic insulin 
resistance with serum elevations of both insulin and sometimes glucose and 
HbA1c.  Measures of hyperinsulinemia and hyperglycemia are accepted measures 
of insulin resistance.  Fasting glucose and insulin, and hemoglobin A1c (HbA1c) 
will be measured 
4. Exploratory biomarkers for aspects of safety and efficacy, including in the 
additional 12 to <18 years age group: suppression of the gonadal axis (LH, FSH) 
and suppression of the thyroid axis (TSH, FT4)  
2.2.5. 
Endpoints for Patient-Reported Outcomes 
Safety endpoints based on subject reports of AEs are listed in Section 2.2.1.   
Additionally, subjects’ parent(s)/legal guardian(s) will be asked to complete the PODCI 
physical function assessment (see Section 7.4.1), and the PARS III behavioral assessment 
(see Section 7.4.2).   
The parent(s)/legal guardian(s) of each subject in the 2 to <4 years age group will be 
asked to complete the Ease of Study Medication Administration Assessment (see 
Section 7.4.3); subjects in the 7 to <18 years age group will complete the Study 
Medication Acceptability Assessment (see Section 7.4.4).   
No other patient-reported outcomes are planned.   

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3. 
STUDY DESIGN 
3.1. 
Overall Study Design 
This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical 
functioning of vamorolone (the investigational medication) 2.0 mg/kg, and 6.0 mg/kg 
administered daily by liquid oral suspension over a treatment period of 12 weeks in 
steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated and currently untreated 
boys ages 7 to <18 years with DMD.   
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day Pretreatment 
Baseline Period; a 3-month Treatment Period (Weeks 1 to 12); and up to8 weeks  for the 
Dose-tapering Period (for subjects who will not transition directly to further vamorolone 
or standard of care (SoC) glucocorticoid treatment at the end of the study  
Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent is obtained.  Within the 2 to <4 years age group, the initial 10 eligible 
subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 
Visit.  The subsequent 10 eligible subjects will be assigned to the 6.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit. 
Within the 7 to <18 years age group (which is including an additional 12 to <18 years age 
group), both corticosteroid-treated and untreated, the initial 12 eligible subjects will be 
assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  The 
subsequent 22 eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at 
the Baseline Day -1 Visit. 
The first 6 subjects in each age group at 2.0 mg/kg will serve as the PK/safety run-in 
cohorts. PK assessments will be performed at Week 2 and, together with the safety 
assessment during the first 4 weeks of treatment, will be the basis to confirm whether 2.0 
and 6.0 mg/kg/day will be used in the subsequent patients or if a dose adjustment is 
needed to avoid over or under-exposure in patients for any of the two age groups. 

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The 7 to <18 years age group will be further stratified by glucocorticoid treatment status 
at study entry, with assignment of subjects 1:1:1:1 to groups: 1. Glucocorticoid-treated 
subjects, 2.0 mg/kg/day treatment group; 2. Glucocorticoid-treated subjects, 6.0 
mg/kg/day treatment group; 3. Glucocorticoid-untreated subjects 2.0 mg/kg/day treatment 
group; 4. Glucocorticoid-untreated subjects 6.0 mg/kg/day treatment group. An additional 
group of 10 glucocorticoid-treated 12 to <18 years subjects will be assigned to the 6 
mg/kg/day treatment.  Glucocorticoid-treated subjects in the 7 to <18 years age group 
will take their final dose of SoC glucocorticoid therapy for DMD on Baseline Day -1, 
within 24 hours prior to administration of the first dose of vamorolone study medication.   
All subjects will begin their assigned vamorolone treatment on Treatment Period Day 1 
and will continue to receive their assigned vamorolone treatment throughout the duration 
of the 3month- Treatment Period (Weeks 1-12).   
At the end of the 3-month Treatment Period (Week 12), subjects will be given the option 
to receive vamorolone in an expanded access or compassionate use program, if possible, 
or to transition to SoC treatment for DMD (may include glucocorticoids).  Subjects 
completing VBP15-006 and enrolling directly into the expanded access or compassionate 
use program or transitioning directly to SoC glucocorticoid treatment will not need to 
taper their vamorolone dose prior to participation in the expanded access or 
compassionate use program or initiation of SoC glucocorticoid treatment.  All subjects 
who will not transition directly to further vamorolone or SoC glucocorticoid treatment 
will begin the  Dose-tapering  Period during which the dose of study medication will be 
progressively reduced and discontinued.  
3.2. 
Study Summary 
This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical 
functioning vamorolone (the investigational medication) over a treatment period of 
12 weeks in steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated and 
currently untreated boys ages 7 to <18 years with DMD.   

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A total of approximately 10 subjects ages 2 to <4 years will be assigned to receive 
vamorolone 2.0 mg/kg/day.  After the first 6 subjects have enrolled at this dose level, the 
pharmacokinetics of vamorolone after 2 weeks of treatment and the safety of vamorolone 
during the first week of administration will be assessed. If the vamorolone exposure in 
terms of AUC is close to the expected target exposure of approximately 1200 ng.h/mL 
(reference value from 2.0 mg/kg given to 4 to 7-year-old boys in VBP15-004) dosing will 
proceed as planned with 2.0 mg/kg/day for the remainder of this group and enrollment of 
the subsequent 10 subjects ages 2 to <4 years assigned to receive 6.0 mg/kg/day can 
proceed. If the vamorolone exposure at 2.0 mg/kg/day in the initial 6 patients of this age 
group deviates substantially from the target or if unexpected safety signals are observed, 
the doses for vamorolone for the subsequent subjects can be adjusted to avoid over- or 
under exposure and to achieve a consistent vamorolone AUC across the entire pediatric 
age range.After the planned DSMB review of the PK and safety data from the safety and 
PK run-in, subjects receiving 2 mg/kg/day can increase the vamorolone dose up to the 
confirmed high dose level if deemed appropriate by the investigator. 
A total of approximately 34 subjects ages 7 to <18 years will be assigned to receive 
vamorolone 2.0 mg/kg/day (glucocorticoid-untreated at study entry), 2.0 mg/kg/day 
(glucocorticoid-treated at study entry), 6.0 mg/kg/day (glucocorticoid-untreated at study 
entry), or 6.0 mg/kg/day (glucocorticoid-treated at study entry) (n=6 per dose level and 
glucocorticoid treatment status group plus n=10 for the additional 12 to <18 years age 
group [6.0 mg/kg/day - glucocorticoid-treated]).  The dose cohort of 2.0 mg/kg/day will 
be enrolled first and the PK and safety assessment from the first 6 subjects in this age 
group will be used to confirm the doses for the subsequent subjects following the same 
process as described for the younger age range.Subjects will be assessed for safety and 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical 
functioning at scheduled visits throughout the study (see Section 6 for a schedule of 
study assessments).  Screening assessments will be performed prior to assignment to a 
dose group.  All subjects will be assigned to treatment at the Baseline Day -1 Visit.   
After completion of Screening and Baseline assessments, and assignment to a dose group 
for treatment, subjects will return to the study clinic on Day 1 for safety, PK, and PD 

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assessments prior to administration of the first dose of study medication.  Additional 
study visits will occur at Week 2, Week 6, and Week 12.   
The dose cohort of 2.0 mg/kg/ will be enrolled first and the PK of vamorolone after 2 
weeks of treatment and the safety of vamorolone during the first week of administration 
from the first 6 subjects in this age group will be used to confirm the doses for the 
subsequent subjects following the same process as described for the younger age range. 
If the vamorolone exposure at 2.0 mg/kg in the initial 6 patients of this age group 
deviates substantially from the target or if unexpected safety signals are observed, the 
high doses level for vamorolone for the subsequent subjects may be adjusted.  
Adverse events, including serious adverse events (SAEs), and concomitant medications 
will be recorded throughout the study.  A Data and Safety Monitoring Board (DSMB) 
will review SAEs and other pertinent safety data at regular intervals during the study and 
make recommendations to the Sponsor regarding study conduct.   
If the intended dose of vamorolone is 6mg/kg, but patients weigh 50 kg or more, the daily 
dose should be capped at 300mg/day. Considering the linearity of vamorolone 
pharmacokinetics, if the patient is dosed at 2mg/kg, the dose is capped at 100mg daily for 
patients weighing 50 kg and above.  
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next day 
on Treatment Period Day 1. For all subjects, daily study drug dosing during the 
Treatment Period will occur from the date of the Day 1 Visit through the date of the 
Week 12 Visit (see Section 5.3).  Study drug dosing will occur at home on all days 
except dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when dosing will occur 
at the study site.  
Subject diaries will be dispensed at the Day 1, Week 2, Week 6, and Week 12 Visits (for 
subjects participating in the Dose-tapering Period) to record AEs, changes to concomitant 
medications taken during the study, and any missed or incomplete doses of study 
medication. 

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The scheduled Week 12 assessments may be performed over a 2-day period, if necessary, 
to facilitate scheduling.  The scheduled 12-lead ECG, eye examination, PODCI, and 
PARS III may be completed on the day prior to the final Week 12 dose of study 
medication; alternatively, these assessments may be performed on the date of the final 
Week 12 dose of study medication.  The scheduled physical examination, weight, height, 
vital signs, clinical laboratory tests, blood draws for PD biomarker analysis, Ease of 
Study Medication Administration Assessment (ages 2 to <4 years only)/Study 
Medication Acceptability Assessment (ages 7 to <18 years only), functional assessments 
(Bayley-III Gross Motor scale [ages 2 to <4 years] and PUL Test [ages 7 to <18 years]), 
recording of AEs/SAEs and concomitant medications, and return of subject diaries should 
be performed on the date of the final Week 12 dose of study medication.  
Subjects who complete the VBP15-006 study assessments through the Week 12 Visit 
may be given the opportunity to continue to receive vamorolone as part of an expanded 
access or compassionate use program under separate protocol, or alternatively transition 
to SoC treatment (including glucocorticoids) for DMD.  Standard of care treatment for 
DMD may be offered to the subject following completion of the VBP15-006 study if the 
subject, or subject’s parent(s) or guardian(s) does not wish to enroll the subject in the 
expanded access or compassionate use program and/or the Investigator feels it to be in 
the best interest of the subject.   
Subjects who complete the VBP15-006 study and will enroll directly into the expanded 
access or compassionate use program to continue vamorolone treatment or will transition 
directly onto SoC glucocorticoid treatment for DMD will be discharged from the 
VBP15-006 study following completion of all Week 12 assessments.  Subjects who will 
not continue vamorolone treatment in the expanded access or compassionate use 
program, and who will not transition directly to SoC glucocorticoid treatment for DMD , 
will have their vamorolone dose tapered during the  Dose-tapering Period- prior to 
discharge from the study..  Site study staff will contact the parent(s)/guardian(s) by 
telephone at Week 14 to ensure that the dose tapering is proceeding according to protocol 
(see Section 6.3.5), to assess potential signs or symptoms of adrenal  insufficiency, and to 
address any questions the parent(s)/guardian(s) may have.. In the event that any clinical 

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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 VBP15-006 study prior to the Week 12 Visit should 
return to the study unit for scheduled Week 12 assessments at the time of early 
withdrawal, whenever possible, assuming the subject has not withdrawn consent.  Any 
subject who withdraws early from the study after study medication dosing has begun and 
will not transition directly to SoC glucocorticoids should undergo dose-tapering (see 
Section 6.3.5) following early completion of the Week 12 assessments.  
3.3. 
Dose Group Assignment 
Following consent, completion of all Screening assessments, and review of study entry 
criteria to confirm subject eligibility for the study, the subject may be assigned to 
treatment at the Baseline Day -1 Visit.   
Subjects in the 2 to <4 years age group will be initially assigned to the 2.0 mg/kg/day 
treatment group.  After this treatment group is fully enrolled (n=10) and after 
pharmacokinetics and safety in the initial 6 children is evaluated and the doses are 
confirmed, then enrollment into the 2 to <4 years age group assigned to the planned 6.0 
mg/kg/day treatment group will take place. 
Similarly, subjects in the 7 to <18 years age group will be assigned to the 2.0 mg/kg/day 
treatment groups first, then subsequently assigned to the planned 6.0 mg/kg/day treatment 
groups. A total of approximately 34 subjects ages 7 to <18 years will be assigned 1:1:1:1 
to receive vamorolone 2.0 mg/kg/day (glucocorticoid-untreated at study entry), 2.0 
mg/kg/day (glucocorticoid-treated at study entry), 6.0 mg/kg/day (glucocorticoid-
untreated at study entry), or 6.0 mg/kg/day (glucocorticoid-treated at study entry) (n=6 
per dose level and glucocorticoid treatment status group plus n=10 for the additional 12 
to <18 years age group [6.0 mg/kg/day - glucocorticoid-treated]). 
Assignment to dose group will require the site investigator, or designee, to verify that the 
subject meets the inclusion/exclusion criteria of the study.  The following information 
will be sent to the TRiNDS Study Coordinator: 

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x Participant’s Study Subject Identification Number 
x Participant’s Age at Enrollment  
x Participant’s glucocorticoid status at entry (7 to <18 years only) 
The Study Coordinator will send an email report with the dose level group assignment, 
and a report generated and sent to the site pharmacy or designated site study staff 
confirming dose and entering the treatment period.  

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4. 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS 
4.1. 
Subject Enrollment and Identification Log 
Subjects will be recruited through the clinics of participating site investigators and other 
mechanisms including patient registries, national and international networks, and patient 
foundations.  After identification of a possible subject, the site investigator will discuss 
the study with the subject’s parent(s) or legal guardian(s).  The subject’s parent(s) or 
guardian(s) will be provided with a copy of the study subject information sheet document 
and allowed time to consider participation prior to signing.  Individuals interested in 
participating will be asked to come to one of the participating study sites to complete the 
informed consent process with a site investigator or designee prior to initiation of 
screening procedures.  Subjects will not be excluded on the basis of race, ethnicity, or 
age, except that the target population for the trial is 2 to <4 years and 7 to <18 years of 
age. 
A subject enrollment log will be maintained at each investigational site for all subjects 
who are screened for the study, including those not assigned to treatment.  Limited data 
will be collected for these subjects, including age at enrollment and reason for exclusion 
from the study.  Subject enrollment logs will be maintained for all subjects enrolled in the 
study.  This record will also include the dates of subject enrollment and 
completion/termination.   
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.  These logs will be reviewed during routine monitoring calls 
and/or visits. 
4.2. 
Inclusion Criteria 
To qualify for participation in this study, the subject must satisfy the following inclusion 
criteria: 
1. Subject’s parent(s) or legal guardian(s) has (have) provided written informed 
consent and Health Insurance Portability and Accountability Act (HIPAA) 

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authorization, where applicable, prior to any study-related procedures; 
participants will be asked to give written or verbal assent according to local 
requirements; 
2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) 
diagnosis of DMD, as defined as: 
x Dystrophin immunofluorescence and/or immunoblot showing complete 
dystrophin deficiency, and clinical picture consistent with typical DMD, OR 
x Identifiable mutation within the DMD gene (deletion/duplication of one or 
more exons), where reading frame can be predicted as ‘out-of-frame,’ and 
clinical picture consistent with typical DMD, OR 
x Complete dystrophin gene sequencing showing an alteration (point mutation, 
duplication, other) that is expected to preclude production of the dystrophin 
protein (i.e., nonsense mutation, deletion/duplication leading to a downstream 
stop codon), with a clinical picture consistent with typical DMD; 
3. Subject is male, 2 to <4 years or 7 to <18 years of age at time of enrollment in the 
study; 
4. If 7 to <18 years of age and currently taking standard of care glucocorticoids for 
treatment of DMD, subject has been taking standard of care glucocorticoids at 
stable dose for at least 3 months prior to enrollment in the study and will continue 
the same stable dose regimen through the date of the Baseline Day -1 Visit.  
[Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 
4 weeks prior to enrollment or if administered at stable dose beginning at least 
4 weeks prior to enrollment and anticipated to be used at the stable dose regimen 
for the duration of the study]; 
5. If 7 to <18 years of age, and not currently glucocorticoid-treated, subject has not 
received oral glucocorticoids or other oral immunosuppressive agents for at least 
3 months prior to enrollment.  [Note: Inhaled and/or topical glucocorticoids are 
permitted if last use is at least 4 weeks prior to enrollment or if administered at 

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stable dose beginning at least 4 weeks prior to enrollment and anticipated to be 
used at the stable dose regimen for the duration of the study]; 
6. Clinical laboratory test results are within the normal range at the Screening Visit, 
or if abnormal, are not clinically significant, in the opinion of the Investigator. 
[Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin 
all must be ≤ upper limit of the normal range at the Screening Visit.  An abnormal 
vitamin D level that is considered clinically significant will not exclude a subject 
from participation]; 
7. Subject has evidence of chicken pox immunity as determined by:  
x Presence of IgG antibodies to varicella, as documented by a positive test result 
from the local laboratory from blood collected during the Screening Period, 
OR 
x Documentation, provided at the Screening Visit, that the subject has had 
2 doses of varicella vaccine, with or without serologic evidence of immunity; 
the second of the 2 immunizations must have been given at least 14 days prior 
to assignment to dose group; and 
8. Subject and parent(s)/guardian(s) 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 participation in this study if he meets any of the 
following exclusion criteria: 
1. Subject has current or history of major renal or hepatic impairment, diabetes 
mellitus or immunosuppression; 
2. Subject has current or history of chronic systemic fungal or viral infections; 
3. Subject has used mineralocorticoid receptor agents, such as spironolactone, 
eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), 
or mexrenone (mexrenoate potassium) within 4 weeks prior to enrollment; 

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4. Subject has a history of primary hyperaldosteronism; 
5. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic 
cardiac abnormality on investigation would not be exclusionary]; 
6. If 2 to <4 years of age, 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 1 month cumulative, with last use at least 3 months prior to 
enrollment will be considered for eligibility on a case-by-case basis, unless 
discontinued for intolerance.  Inhaled and/or topical glucocorticoids are permitted 
if last use is at least 4 weeks prior to enrollment or if administered at stable dose 
beginning at least 4 weeks prior to enrollment and anticipated to be used at the 
stable dose regimen for the duration of the study]; 
7. Subject has an allergy or hypersensitivity to the study medication or to any of its 
constituents; 
8. Subject has used idebenone within 4 weeks prior to enrollment; 
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 taking (or has taken within 4 weeks prior to enrollment) herbal 
remedies and supplements which can impact muscle strength and function (e.g., 
Co-enzyme Q10, creatine, etc);  
12. Subject is taking (or has taken within 3 months prior to enrollment) any 
medication indicated for DMD, including Exondys51 and Translarna;  
13. Subject has been administered a live attenuated vaccine within 14 days prior to 
the first dose of study medication; 

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14. Subject is currently taking any other investigational drug or has taken any other 
investigational drug within 3 months prior to enrollment; or 
15. Subject has previously been enrolled in the VBP15-006 study or any other 
vamorolone study. 
Note: Any parameter/test may be repeated at the Investigator’s discretion during 
Screening to determine reproducibility.  In addition, subjects may be rescreened if 
ineligible due to negative anti-varicella IgG antibody test result after vaccination has been 
completed  Subjects may be rescreened in case of ongoing medical condition developing 
during the screening period, e.g. acute viral infection, or laboratory abnormality that 
could affect safety if the subject would start vamorolone. In this case, the subject can be 
rescreened after resolution of the medical condition.   
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:  
x The subject’s parent/legal guardian is uncooperative/noncompliant and does not 
adhere to study responsibilities, including failure to attend study visits; 
x Difficulty in obtaining blood samples from the subject for safety monitoring; 
x 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, and may jeopardize the subject’s health; 
x The Sponsor terminates the study; 
x 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 

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reason for withdrawal, the subject will remain under the supervision of the Investigator 
until resolution of the event. 
Any subject who discontinues the study prior to the Week 12 Visit should return to the 
study unit for scheduled Week 12 assessments at the time of early withdrawal, whenever 
possible, assuming the subject has not withdrawn consent.  Any subject who withdraws 
early from the study after study medication dosing has begun and will not transition 
directly to SoC glucocorticoids should undergo dose-tapering following early completion 
of the Week 12 assessments.  Subjects will also be asked to return to the study unit at the 
end of the tapering period for a final study visit.  In the event a subject withdraws 
informed consent, no further study procedures should be performed and no additional 
data should be collected.  Any data collected up to the point of withdrawal of informed 
consent may be used by the Sponsor. 
4.5. 
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 

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4. Failure to adhere to the protocol. 
Subjects who are participating at a given site at the time it is terminated by the Sponsor 
will be offered the opportunity to continue to participate in the study at an alternative 
active site.  Subjects who decline the offer to participate at an alternative active site and 
who will not transition directly to SoC glucocorticoid treatment will need to undergo 
dose tapering at the time the original site is terminated according to the dose-tapering 
schedule (see Section 6.3.5). 

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5. 
TREATMENT OF STUDY SUBJECTS 
5.1. 
Study Medication Administered 
Planned vamorolone dose levels:2.0 mg/kg/day and 6.0 mg/kg/day. Doses can be 
adjusted based on PK and safety data from the first 6 patients per age group to avoid 
over- or under exposure and to achieve a consistent vamorolone AUC across the entire 
pediatric age range.The recommended dose of vamorolone is 6 mg/kg once daily in 
patients weighing less than 50 kg. In patients weighing 50 kg and above, the high dose 
level (6 mg/kg/day) must be capped at 300 mg once daily and the low dose level 
(2mg/kg/day) must be capped at 100 mg once daily.  
Vamorolone will be administered to all subjects as an oral liquid suspension. 
A total of approximately 10 subjects in the 2 to <4 years age group will be enrolled into 
the 2.0 mg/kg/day treatment group.  After the pharmacokinetics and safety is determined 
in the initial 6 subjects and the doses are confirmed, enrollment will continue for 10 
subjects in the 2 to <4 years age group into the planned 6.0 mg/kg/day treatment group.  
A total of approximately 12 subjects in the 7 to <18 years age group will be enrolled into 
the 2.0 mg/kg/day treatment groups (6 untreated at entry, 6 corticosteroid-treated at 
entry).  After the pharmacokinetics and safety is determined in the initial 6 subjects and 
the doses are confirmed, enrollment will continue for 22 subjects in the 7 to <18 years 
age group into the planned 6.0 mg/kg/day treatment group (6 untreated at entry, 6 
corticosteroid-treated at entry plus 10 for the additional 12 to <18 years age group 
(glucocorticoid-treated).  
Vamorolone 4.0% weight per volume (wt/vol) oral suspension (investigational medicine) 
will be administered to all subjects once daily for 12 weeks, from Study Day 1 until the 
Week 12 Visit.  At the end of the 12-week Treatment Period, a subset of subjects may 
receive additional vamorolone treatment in a Dose-tapering Period prior to discharge 
from the study (see Section 6.3.5). 
5.2. 
Identity of Investigational Product 
Santhera will supply the following investigational study medication: 

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Active Substance: 
 
Vamorolone 
Strength: 
 
4.0% wt/vol 
Dosage Form:  
Oral suspension 
Formulation:  
ROS2 
Manufacturer:  
Purna Pharmaceuticals NV/SA 
5.3. 
Dosage Schedule and Administration of Study Medication 
Subjects in the 2 to <4 years age group and subjects in the 7 to <18 years age group will 
be administered vamorolone 4.0% wt/vol oral suspension (Formulation ROS2).   
All subjects will receive study medication, administered orally once daily for 12 weeks, 
from Study Day 1 to the Week 12 Visit.  At the end of the 12-week Treatment Period, 
subjects who will not continue directly with further vamorolone or SoC glucocorticoid 
treatment at the end of the study will be tapered off suspension study medication (Dose-
tapering Period,) prior to discharge from the study (see Section 6.3.5).  
The site pharmacist or designated site study staff will dispense study medication to each  
subject in 125 mL bottles sufficient for 6 weeks of dosing (as needed for Dose-tapering 
Period) plus overage at the Day 1 Visit, just prior to dosing, and at the Week 6 Visit (and 
Week 12 Visit to subjects participating in the Dose-tapering Period), according to the 
subject’s dose assignment and subject body weight (in kg) recorded at the dispensing 
visit (Day -1 weight for Day 1 dispensing) (see Appendix 15.1 for a dose calculation 
worksheet). 
Each subject’s dose (in mL) will be calculated and written on the labels of the bottles to 
be dispensed at a given visit by trained site staff based on the weight of the subject (in kg) 
recorded at the dispensing visit.  The dispensed study medication bottle(s) will be 
returned to the study site at each subsequent scheduled study visit.  Study medication 
suspension dispensed at the Day 1 Visit should be brought in with the subject to the 
Week 2 Visit, for Week 2 dosing in -clinic and compliance monitoring; this study 
medication will be returned to the subject at the end of the Week 2 Visit for continued 

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dosing through the Week 6 Visit; new study medication will not be dispensed at the 
Week 2 Visit.  
All subjects will receive all doses under the supervision of parents or legal guardians or 
trained study staff.  Dosing is to occur at home throughout the 12-week Treatment Period, 
except at the Day 1, Week 2, Week 6, and Week 12 Visits when dosing will occur at the 
study site.  Subjects should receive each dose of study medication in the morning 
together with breakfast and at approximately the same time of day. On days where 
vamorolone is administered in clinic, subjects should arrive fasted for >6 hours and 
should eat breakfast with their dose of study drug.   
Vamorolone suspension will be administered orally using a volumetric syringe supplied 
by the site.  Following administration of the dose of study drug suspension, 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 breakfast.  There are no other food or drink restrictions 
before or after dosing.   
At the Day 1, Week 2, Week 6, and Week 12 study visits, subjects will arrive at the study 
clinic and will eat breakfast at the study site after collection of fasting lab samples and 
within 30 minutes prior to administration of the dose of study medication. 
Any missed or incomplete doses of study medication should be recorded in the Subject 
Diary and reported immediately to the site Investigator. 
5.4. 
Rationale for Dose Selection 
Dose levels of the investigational medication were chosen for this study to ensure the 
safety of subjects participating in the study, to allow suitable population PK assessment 
and demonstration of PD effects, and to evaluate clinical efficacy.   Vamorolone at doses 
of 0.25 mg/kg/day, 0.75 mg/kg/day, 2.0 mg/kg/day, and 6.0 mg/kg/day has been 
demonstrated to be safe and well-tolerated in 48 DMD boys ages 4 to <7 years (12 
subjects at each dose level) in a 2-week Phase IIa study (VBP15-002), and a 24-week 

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Phase II extension study (VBP15-003).  The safety of these doses were also evaluated in 
the same subjects in the ongoing VBP15-LTE 24-month extension study.  The safety of 
the 2.0 mg/kg/day and 6.0 mg/kg/day doses is also being studied in a recently completed 
52-week double-blind, comparator- and placebo-controlled study (VBP15-004) in 120 
subjects receiving vamorolone 2.0 mg/kg/day, vamorolone 6.0 mg/kg/day, prednisone 
0.75 mg/kg/day or placebo for the first 24 weeks of the study, and then vamorolone 
2.0 mg/kg/day or vamorolone 6.0 mg/kg/day for the final 24 weeks of the study.   
There were a total of 4 SAEs in the Phase II VBP15-003 study, three SAEs to date in the 
VBP15-LTE extension study, and one SAE to date in the VBP15-004 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, one SAE of influenza-associated dehydration in a 
subject receiving 6.0 mg/kg/day, two SAEs of acute myoglobinuria in a subject receiving 
6.0 mg/kg/day, and one SAE of viral gastroenteritis in a subject receiving blinded study 
drug, who was admitted to the hospital for dehydration.  Each of these SAEs was 
considered unrelated to study drug, and none of them resulted in discontinuation from the 
study.   
One subject receiving vamorolone 6.0 mg/kg in the Phase II extension study 
(VBP15-003) who had an incidental early morning cortisol drawn following an AE of 
presyncope had evidence of 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.  
Thus, based on the available data in the VBP15-003 study regarding the safety signal of 
suppression of the adrenal axis, the possibility of adrenal suppression is present in 
subjects at the 2.0 and 6.0 mg/kg/day dose levels.   
The results of the VBP15-003 24-week extension study and the interim results of the 
ongoing 24-month VBP15-LTE study suggest that doses of vamorolone of 2.0 mg/kg/day 

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and 6.0 mg/kg/day produced significant enhancement of muscle strength, mobility, and 
functional exercise capacity.   
The results of the VBP15-004 24-week double-blind, placebo- and prednisone-controlled 
study showed that doses of vamorolone 2.0 mg/kg/day and 6.0 mg/kg/day showed 
significant enhancement of muscle strength, mobility, and functional exercise capacity 
vs. placebo.  This study showed that doses of vamorolone 2.0 mg/kg/day and 6.0 
mg/kg/day did not cause the stunting of growth and deleterious changes in bone 
biomarkers seen with prednisone in this head-to-head comparison. Additional efficacy 
and safety results can be found in the current IB.  
Based on the safety and efficacy results observed in these earlier studies in DMD boys 
aged 4 to 7 years, doses of vamorolone at 2.0 mg/kg/day and 6.0 mg/kg/day were chosen 
for evaluation in the current study enrolling younger and older subjects. For the 6 mg/kg, 
a cap dose of 300 mg once daily has been established for children weighing more than 50 
kg based on pharmacokinetic modeling to account for the expected high pharmacokinetic 
exposures due to growth and maturation of the pediatric population. Since the effect of 
age on the pharmacokinetics of vamorolone is not yet established and since this is the 
first time that the to-be-marketed formulation of ROS2 will be administered to DMD 
boys, a PK/safety run-in at 2.0 mg/kg/day is included into the study to evaluate the PK 
and safety in subjects 2 to <4 and 7 to <18 years of age and to adjust the doses if needed 
to avoid over- and underexposure of vamorolone in these age groups and to ensure a 
consistent vamorolone AUC across the entire pediatric age range.  All doses of 
vamorolone will be administered in the morning with breakfast.   
5.5. 
Treatment Compliance 
Subject compliance with the dosing schedule will be assessed by site maintenance of 
accurate study drug dispensing and return records, and accurate recording of incomplete 
or missed doses by completion of a diary by the subject’s parent or guardian.  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(s) or guardian(s) 
with regard to proper dosing of study medication and completion of subject diaries and 

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will reinforce the importance of taking all study medication per protocol instructions.  
Doses of study drug on the days of the Day 1, Week 2, Week 6, and Week 12 Visits will 
be administered at the participating study site by a trained investigational staff member.  
All incomplete or missed doses are to be documented in the source document and on the 
appropriate eCRF page.  The volume of unused study medication remaining in each 
bottle returned, as measured by the weight of returned bottles, will be documented in the 
source documents and on the appropriate eCRF page. 
5.6. 
Study Drug Dose Interruption or Discontinuation 
Subjects whose study medication is interrupted should continue to follow the original 
schedule and timing of study visits.  Study staff should contact the Study Chair or 
Medical Monitor at the time of dose interruption for any additional instructions for 
visit -specific assessments. 
In the event any clinical observation suggests an intolerability of an individual subject to 
the study medication, in the opinion of the Investigator, the case should be discussed with 
the Medical Monitor within 24 hours and study drug discontinuation should be 
considered.  In view of the potential effect of the study drugs on adrenal glands, the study 
drugs cannot be discontinued suddenly.  In case study drug needs to be discontinued, for 
whatever reason, the dose tapering process described for the end of the treatment period 
should be followed.  If a subject discontinues study drug due to intolerability, the subject 
will be withdrawn from the study.  The subject should return to the study site for 
completion of Week 12 assessments at the time of early withdrawal, prior to participation 
in the Dose -tapering Period, as appropriate.  Any AE still ongoing at the time of study 
drug discontinuation will be monitored until it has returned to baseline status, stabilized, 
or the Investigator and Sponsor agree that follow-up is no longer needed.  
5.7. 
Prior and Concomitant Medications and Therapies 
5.7.1. 
Prior Therapy 
All medications (prescription and over-the-counter [OTC]) taken within 3 months prior to 
the Screening Visit through Baseline Day -1 (until just prior to administration of the first 

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dose of study medication) will be captured as prior medications (Medication History) in 
the source document and the eCRF, including the name of the medication (or device or 
procedure), the dosage and regimen, the indication, and the treatment start and stop dates.  
All past (lifetime) steroid use will be recorded.   
5.7.2. 
Concomitant Therapies 
Any medications that are taken after administration of the first dose of study medication 
will be recorded as concomitant medications on the appropriate eCRF page.  Subject 
diaries will be provided to subjects to record any concomitant medication changes during 
the study (see Section 7.5).  
All medications (prescription and OTC) taken during the 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 (i.e., DMD or non-DMD), 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. 
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: 
x Mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone 
(canrenoate potassium), prorenone (prorenoate potassium), and mexrenone 
(mexrenoate potassium): use must be discontinued at least 4 weeks prior to 
enrollment; 
x Oral glucocorticoids or other immunosuppressive agents.  Subjects in the 2 to <4 
years age group who have received prior treatment with oral immunosuppressive 

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agents are ineligible for study entry.  [Note: Past transient use of oral 
glucocorticoids or other oral immunosuppressive agents for no longer than 
1 month cumulative, with last use at least 3 months prior to enrollment, will be 
considered for eligibility on a case-by-case basis, unless discontinued for 
intolerance.]  Subjects in the 7 to <18 years age group who have been receiving 
SoC glucocorticoids for treatment of DMD for at least 3 months prior to 
enrollment in the study will continue the same stable dose regimen through the 
date of the Baseline Day-1 Visit; the SoC glucocorticoids must be discontinued on 
Day 1.  Subjects in the 7 to <18 years age group who are not currently receiving 
oral glucocorticoids or other oral immunosuppressive agents must have 
discontinued all such agents at least 3 months prior to enrollment.  [Note: Inhaled 
and/or topical glucocorticoids are permitted but must be administered at stable 
dose beginning at least 4 weeks prior to enrollment, and anticipated to be used at 
the stable dose regimen for the duration of the study.] 
x Idebenone: use must be discontinued at least 4 weeks prior to enrollment; 
x Live attenuated vaccines: use must be avoided within 14 days prior to first dose of 
study medication and for the duration of participation in the study; 
x Any investigational medications other than vamorolone: use must be discontinued 
at least 3 months prior to enrollment; 
x Other medications indicated for the treatment of DMD, including Exondys 51 and 
Translarna: use must be discontinued at least 3 months prior to enrollment; 
x Any approved medications or herbal remedies which can impact strength and 
function (including, but not limited to, Co-enzyme Q10 and creatine): use must be 
discontinued at least 4 weeks prior to enrollment. 
In addition, vamorolone should be used with caution with any drug metabolized by 
cytochrome P450 3A4 (CYP3A4). 
The Investigator should contact the Study Chair and Medical Monitor 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 start 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.  
5.7.5. 
Hydrocortisone 
All subjects should be covered with “stress dosing” of hydrocortisone (or prednisone) 
during times of illness, injury, or surgery.  Hydrocortisone dosing will be recorded in the 
source document and in the eCRF. 
5.7.6. 
Vitamin D 
Serum Vitamin D levels will be measured at Screening and at the Week 12 Visit.  
Vitamin D insufficiency and deficiency (i.e., serum 25[OH] D concentration less than 
20 ng/mL [50 nmol/L]) will be treated with high doses of Vitamin D supplement 
according to local site guidelines.  Vitamin D supplements will be recorded in the source 
document 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.  The Study Sponsor through the designated central pharmacy 
will provide CTM in bulk quantities sufficient to satisfy the protocol requirement.  
Vamorolone 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 125 mL (4 oz) amber bottles with a 100 mL fill volume 
with child-resistant cap with a 28 mm bottle press-in adapter.  

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Bottles of investigational medication suspension will contain 4.0 grams of 
vamorolone/100 mL (4.0% orange-flavored suspension).   
Bulk drug supplies will be labeled with the Sponsor name, protocol number, lot number, 
expiration or retest date, and other appropriate study information.  Carton and bottle 
labels will be written in accordance with all applicable laws, guidance and directives of 
the jurisdiction where the study is being conducted.  
The volume per dose to be administered to each subject depends on the subject’s weight 
(in kg) recorded at the dispensing visit; see Appendix 15.1 for complete instructions on 
calculating dose volume.   
Trained site staff will write the dose level, dose volume in mL, and dispense date on the 
bottle label, prior to dispensing to subjects.  Clinical supplies dispensed by the study site 
staff and ready for administration to subjects will be labeled with the dispense date, 
vamorolone dose level, volume to be administered per dose, protocol number, and 
additional information as required by all applicable laws, guidance and directives of the 
jurisdiction where the study is being conducted. 
Each study medication bottle may be used for a single subject only.   
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 CTM should be stored at refrigerated temperature (2oC - 
8oC; 36oF - 46oF).  Excursions to ambient temperature are allowed (see Pharmacy Manual 
for details).   
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 

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procedures.  Study sites will receive CTM in bulk in sufficient quantity to satisfy the 
protocol requirements.   
Clinical trial material will only be dispensed to the subject once the subject’s 
parent/guardian has (1) a signed informed consent form (ICF) and HIPAA (as applicable) 
authorization on file, (2) met all eligibility criteria for entry into the study, (3) completed 
all Pretreatment requirements, and (4) been assigned to treatment. 
It is essential to this study that all CTM be accounted for during the study period.  All 
unused (i.e., undispensed; dispensed and returned) study medication will be retained at 
the study site for reconciliation by the Sponsor's study monitors (or designees) during 
routine monitoring visits.  Final disposition of all unused CTM will be coordinated by the 
Sponsor's study monitors (or designees) throughout and 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 assigned to treatment 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 (or designee) and hospital pharmacists, 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. 
At the Baseline (Day -1) Visit, subjects will be assigned to treatment by communication 
with the TRiNDS Study Coordinator.  At the Day 1 Visit, the trained site staff will record 
the dose level, volume in mL per suspension dose, and dispense date on the bottle 
label(s).  Labeled study drug supplies sufficient to last until the Week 6 Visit will be 
dispensed to each subject.  The first dose of study medication will be administered in 
clinic on Study Day 1.  The initial drug supply will be sufficient to allow for the Week 6 
Visit to occur on the latest date permissible within the protocol -specified visit window (6 
weeks ± 3 days).  No additional study drug supplies will be dispensed at the Week 2 
Visit. 

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Additional bulk CTM supply will be packaged, labeled (as described above) and 
couriered to the site as needed to satisfy enrollment.   
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: 
x 
The Subject Identification (ID) number of the subject to whom the study drug 
was dispensed 
x 
The date(s) and quantity of the study drug dispensed to the subject 
x 
The weight (g) of the dispensed bottle(s) 
x 
The date(s) and quantity of the study drug returned by the subject 
x 
The weight (g) of the returned bottle(s). 
All records and drug supplies must be available for inspection by the Study Monitor at 
every monitoring visit.  Unused medication will be returned to Santhera or its designee or 
destroyed on site at the end of the study or at a specific time in agreement with the 
Sponsor, as coordinated between the site and Santhera or its designee.  The completed 
Drug Dispensing Log and Drug Return Record(s) will be returned to Santhera or its 
designee.  The Investigator’s copy of the Drug Return Record(s) must accurately 
document the return of all study drug supplies to Santhera or its designee. 
5.9. 
Procedures for Assigning Subject Identification Numbers 
This is a non-randomized, open-label study.  Following the signing of the written 
Informed Consent Form (ICF), subjects will be assigned, by age group (and by 
glucocorticoid treatment status at entry for subjects in the 7 to <18 years age group), a 
unique site-specific 6-digit subject ID number in sequential order of screening into the 
study.  The site will notify the TRiNDS Coordinating Center  of the newly assigned 
subject number.  

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All data for all subjects whose parent(s) or guardian(s) signs the ICF for the study will be 
identified using the unique 6-digit subject ID number.  Subjects are considered to be 
enrolled in the study when the parent(s) or guardian(s) signs the study specific ICF at 
Screening.   
These subject ID numbers assigned upon signing of the written ICF will be retained 
through enrollment and throughout participation in the study.  Subject ID numbers 
assigned to subjects who fail screening may not be used again.   
The Site Investigator will keep a record relating the names of the subjects to their ID 
numbers (subject identification log) to permit efficient verification of data subject files, 
when required.  A subject enrollment log will 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:  
x Pretreatment Screening Period:  The up-to-32-day interval, from subject’s 
parent(s) or guardian(s) signing of the Informed Consent/HIPAA authorization 
until completion of all designated screening procedures, at least 24 hours prior to 
the first dose of study medication.  All screening procedures must be completed 
by Day -1. 
x Pretreatment Baseline Period:  The 24-hour period immediately prior to 
administration of the first dose of study medication (Day -1).  Subjects meeting all 
eligibility criteria will be assigned to a treatment group on Baseline Day -1, within 
24 hours prior to administration of the first dose of study medication. 
x Treatment Period:  The 12-week interval starting with administration of the first 
dose of study medication on Study Day 1 and continuing through the time of 
completion of all scheduled Week 12 Visit assessments.  Subjects who will 
continue directly with further vamorolone or SoC glucocorticoid treatment will be 
discharged from the study following completion of all scheduled Week 12 
assessments. 
x Dose-tapering Period: The interval following the end of the 12-week Treatment 
Period during which subjects who will not transition directly to further 
vamorolone or SoC glucocorticoid treatment will begin  a Dose tapering-period 
during which the dose of study medication will be progressively reduced and 
discontinued (see Section 6.3.5).  Subjects will be discharged from the study 
following completion of all final Dose-tapering Period assessments.   
x The procedures to be completed at each visit during each study period are 
presented in the Schedule of Study Activities (Table 2) and in the sections that 
follow.  (Note: For each visit the acceptable time window around the planned visit 

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date, where applicable, is provided.)  Detailed descriptions of the assessments and 
the definitions of study endpoints are provided in Section 7 and Section 2, 
respectively.  Any deviation from study procedures should be noted in the source 
documents and in the Clinical Trial Management Software (CTMS), and 
significant deviations should be reported immediately to the Sponsor.   
x Overall, up to approximately 21 weeks are allocated for each subject to complete 
the study, including a 32-day Pretreatment Screening Period, a one-day 
Pretreatment Baseline Period, a 12-week Treatment Period, plus a Dose -Tapering 
Period, as applicable.  Upon the completion of the study, subjects may have the 
option to receive additional vamorolone treatment by enrolling in an expanded 
access or compassionate use program. 
x Subjects who continue directly with vamorolone treatment by expanded access or 
compassionate use or who transition directly to SoC glucocorticoid treatment for 
DMD will be discharged from the VBP15006 study following completion of all 
Week 12 assessments and will not participate in the Dose tapering Period. 
x Subjects who do not enroll directly into an expanded access or compassionate use 
program and who do not transition directly to SoC glucocorticoid treatment for 
DMD will participate in the Dose-tapering Period and will be discharged from the 
VBP15006 study following completion of all Dose tapering Period assessments. 
Table 2. 
Schedule of Study Activities 
 
Pretreatment Period 
 
Treatment Period 
Dose-tapering 
Perioda 
 
SCR 
BL 
 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b 
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Informed consent 
X 
 
 
 
 
 
 
 
Enrollmentf 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
Assignmentg 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 

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Pretreatment Period 
 
Treatment Period 
Dose-tapering 
Perioda 
 
SCR 
BL 
 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b 
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Medication history 
X 
X 
 
 
 
 
 
 
Physical examination 
X 
Xee 
 
 
X 
X 
 
X 
Cushingoid features 
X 
X 
 
 
X 
X 
 
X 
Heighth 
X 
 
 
 
 
X 
 
 
Weight 
X 
X 
 
X 
X 
X 
 
X 
Vital signsi 
X 
X 
Xj 
X 
X 
X 
 
X 
Blood for clinical 
labsk 
X 
 
Xl 
 
Xl 
Xl 
 
X 
Blood for vitamin D 
X 
 
 
 
 
Xl 
 
 
Confirmation of 
varicella immunity 
X 
 
 
 
 
 
 
 
Urinalysism 
X 
 
X 
 
X 
X 
 
X 
Blood for serum PD 
biomarker paneln 
 
 
Xl 
 
 
Xl 
 
 
Fasting blood for 
insulin, glucose 
 
 
Xl 
Xl 
Xl 
Xl 
 
 
Blood for HbA1c 
X 
 
 
 
 
Xl 
 
 
Blood for morning 
cortisolo 
 
 
Xl 
 
 
Xl 
 
 
Blood for Plasma PK 
 
 
Xp 
Xp 
 
 
 
 
12-lead ECGq 
X 
 
 
 
 
X 
 
 
Eye examination 
X 
 
 
 
 
X 
 
 
Dispense study 
medication 
 
 
X 
 
X 
Xr 
 
 
Return study 
medication/ 
compliance 
monitoring 
 
 
 
Xs 
X 
X 
 
X 
Study medication 
dosingt 
 
 
X 
 
 
X 
 
 
Study medication 
dose tapering 
 
 
 
 
 
Xr 
 
X 
Telephone call to 
subject 
 
 
 
 
 
 
Xu 
 
Bayley-III Gross 
Motorv 
X 
X 
 
 
 
X 
 
 
PUL Testw 
X 
X 
 
 
 
X 
 
 
Pediatric Outcomes 
Data Collection 
Instrument (PODCI) 
X 
 
 
 
 
X 
 
 
PARS III 
X 
 
 
 
 
X 
 
 

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Pretreatment Period 
 
Treatment Period 
Dose-tapering 
Perioda 
 
SCR 
BL 
 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b 
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Ease of Study 
Medication 
Administration 
Assessmentx 
 
 
 
 
X 
X 
 
 
Study Medication 
Acceptability 
Assessmenty 
 
 
 
 
X 
X 
 
 
Dispense subject 
diariesz 
 
 
X 
X 
X 
Xq 
 
 
Return subject diaries 
 
 
 
X 
X 
X 
 
X 
AE/SAE recordingaa 
X 
 
 
 
 
 
 
Xbb 
Prior/Concomitant 
medications 
X 
 
 
 
 
 
 
X 
Discharge from study 
 
 
 
 
 
Xcc 
 
Xdd 
BL = Baseline; d = day(s); SCR = Screening.  
a. 
Only subjects who will not transition directly to further vamorolone or SoC glucocorticoid 
treatment at the end of the 12-week Treatment Period will begin a  Dose tapering Period during 
which the dose of study medication will be progressively reduced and discontinued. 
b. All Day -1 assessments must be completed within 24 hours prior to administration of the first dose 
of study medication on Day 1.  
c. 
Time windows around the Week 2, Week 6, and Week 12 Visits are allowances from date of Day 
1 Visit; time window around Week 16 Visit is allowance from date of Week 12 Visit. 
d. Subjects who prematurely discontinue from the study prior to Week 12 should complete the 
Week 12 assessments at the time of early withdrawal and undergo Dose-tapering, where 
appropriate.   
e. 
Subjects will have one study site visit during the Dose-tapering Period, at one week after the dose 
of study medication has been discontinued (Week 16).  
f. 
Subjects are considered to be enrolled in the study at the time written informed consent is 
obtained. 
g. Assignment to a treatment group is done by the TRiNDS Study Coordinator at the Baseline Day -1 
Visit. 
h. Standing height will be measured for subjects in the 2 to <4 years age group and participants ages 
7 to <18 years who can stand independently; ulnar length will be measured and used to calculate 
height for subjects in the 7 to <18 years age group. 
i. 
Sitting blood pressure, body temperature, respiratory rate, and heart rate. 
j. 
Vital signs recorded prior to administration of the first dose of study drug at the Day 1 Visit. 
k. Blood for hematology, chemistry, and lipids. All samples should be collected after subject has 
fasted for >6 hours.  
l. 
Blood samples collected after subjects have fasted for ≥ 6 hours, and prior to daily dose of study 
drug.   
m. Urinalysis by dipstick and microscopic analysis. 

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n. Blood collected for PD biomarkers at Day 1 pre-dose and Week 12 predose includes exploratory 
safety outcomes of bone turnover (osteocalcin, CTX, P1NP), as well as in the additional 12 to <18 
years age group, suppression of the gonadal axis (LH, FSH) and suppression of the thyroid axis 
(TSH, FT4).  Blood remaining from collected blood samples not needed for protocol-specified 
analyses may be stored for future exploratory biomarker studies for aspects of safety and efficacy.  
All pre-dose samples should be collected after subject has fasted for ≥ 6 hours.   
o. Blood collected for morning cortisol should be collected before 10 AM local time. 
p. Blood samples for population PK analysis will be collected within 30 minutes pre-dose and at 1, 2, 
and 6 hours post-dose at the Day 1 and Week 2 Visits (ages 2 to <4 years), and within 30 minutes 
pre-dose, and at 1, 2, 4, 6 and 8 hours post-dose at the Day 1 and Week 2 Visits (ages 7 to <18 
years). 
q. 12-lead ECG recorded after subject has rested quietly in a supine position for at least 5 minutes. 
r. 
Only for subjects participating in the Dose-tapering Period. 
s. 
Study medication brought by subjects to the Week 2 Visit for dosing and compliance assessment 
will be redispensed to subjects at the end of the visit. 
t. 
During the Treatment Period, the dose of study medication on the days of the Day 1, Week 2, 
Week 6, and Week 12 Visits will be administered with breakfast in the study clinic.  All other 
doses will be taken with breakfast at home.   
u. Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to ensure that the 
study drug tapering is proceeding according to protocol, to assess potential signs or symptoms 
indicative of adrenal suppression, and to address any questions the parent(s)/guardian(s) may have.  
v. Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale will be 
completed for subjects in the 2 to <4 years age group only. 
w. Performance of Upper Limb (PUL) test will be performed by subjects in the 7 to <18 years age 
group only. 
x. Ease of Study Medication Administration Assessment will be completed for subjects in the 2 to <4 
years age group only. 
y. Study Medication Acceptability Assessment will be completed by subjects in the 7 to <18 years 
age group only. 
z. 
Subject diaries used to record any changes in concomitant medications taken, any AEs 
experienced during the study, and any incomplete or missed doses of study medication. 
aa. All AEs and SAEs must be recorded in the source documents and eCRF from the date of the 
subject’s written informed consent until the final Week 16 Visit or the subject’s participation in 
the study is completed (SAEs through 30 days after final dose study drug).  Ongoing AEs will be 
followed to resolution, stabilization, or until such time the Investigator believes follow-up is not 
necessary. 
bb. For subjects who do not continue into an expanded access or compassionate use program, site staff 
will make a phone call to the home 31-35 days after the final dose of study medication in 
VBP15-006 Dose-tapering Period to confirm the final SAE status of the subject. 
cc. Subjects who elect to continue vamorolone therapy by enrolling directly into an expanded access 
or compassionate use program or who will transition directly to SoC glucocorticoid therapy may 
be discharged from the study following completion of all final Week 12 assessments. 
dd. Subjects who participate in the Dose-tapering Period may be discharged from the study following 
completion of all final Dose-tapering Visit assessments (Week 16). 
ee. Including Ambulatory status. 
 

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6.2. 
Informed Consent and Assent Procedures  
Subjects are considered to be enrolled in the study at the time written informed consent is 
obtained. 
The parent(s) or guardian(s) of all subjects are to give informed consent in accordance 
with the Declaration of Helsinki, US 21 Code of Federal Regulations (CFR) Part 50, 
International Conference on Harmonisation (ICH) guidelines on GCP and all applicable 
laws, guidances, and directives of the jurisdiction where the study is being conducted. 
The parent(s) or guardian(s) of subjects who choose to enroll in this study will give 
written informed consent during the Screening Period.  The Investigator (or designated 
staff) will obtain the written informed consent from the subject’s parent(s) or guardian(s) 
prior to performing any study-related procedures.  Each subject’s parent(s) or guardian(s) 
will receive an explanation of the nature and purposes of the study from the Investigator 
or designee.  Time will be given to the parent(s)/guardian(s) to ask questions and make 
their decision as to whether they would like for their child to participate.  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(s) or guardian(s) 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(s) or guardian(s) will be asked if s/he understands that 
the subject is free to withdraw from the study at any time without prejudice.  Each 
subject’s parent(s) or guardian(s) will be required to sign a study ICF (and HIPAA 
authorization, if applicable) before any procedures are performed for the study; both 
parents or guardians will sign the ICF in jurisdictions where this is required.   
If applicable, the assent of the child himself will also be obtained, if possible, in writing 
per individual where a child is intellectually capable of assenting (and in accordance with 
local regulations), and with the permission of the parent(s)/guardian(s). 
The Investigator or designee will obtain written informed consent from each subject’s 
parent(s) or guardian(s) prior to the subject’s participation in the study using ICFs 
approved by the appropriate IRB/IEC at each site.  Consent must be obtained in 

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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(s), and the original signed 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 has 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(s).  The study subject’s legal 
representative(s) will receive a copy of the signed consent form. 
6.2.1. 
HIPAA and Protected Health Information  
In the applicable countries, during the informed consent procedure, the Investigator or 
designee will review the elements of the HIPAA and Protected Health Information (PHI) 
with each subject’s parent(s) or guardian(s), and each subject’s parent or guardian will 
confirm that s/he understands HIPAA authorization and PHI.  The Investigator (or 
designated staff) will obtain HIPAA authorization from the subject’s parent(s) or 
guardian(s) on the appropriate IRB/IEC-approved form at each site, prior to any 
study-related procedures.  
6.3. 
Visit Schedule and Procedures 
During the study, there will be a total of up to seven study site visits: Pretreatment 
Screening Visit (screening procedures can be performed on more than one day if 
necessary); Pretreatment Baseline Day -1 Visit; Treatment Period Day 1 and Weeks 2, 6, 
and 12 Visits, and final Dose-tapering Period Week 16 Visit.  In addition, to facilitate 
completion of all required Week 12 assessments, some of the assessments scheduled for 
the Week 12 Visit may be completed on the day prior to the Week 12 dose of study 
medication, if needed (see Section 6.3.4). 
Each subject will receive the assigned, open-label study medication at stable daily dose 
for a period of 12 weeks.  Following completion of the 12-week Treatment Period, all 
subjects who will not be continuing directly to receive vamorolone by expanded access or 

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compassionate use or transitioning directly to SoC glucocorticoid therapy will taper their 
study medication during the Dose-tapering Period (up to 8 weeks) and will return to the 
study site for study assessments at the end of the Dose-tapering Period, See Section 7 for 
a detailed description of the safety, PK, clinical efficacy, PD, behavior and 
neuropsychology, physical functioning, and sleep-wake activity assessments to be 
performed during this study. 
6.3.1. 
Screening Period (Day -33 to -2) 
The Investigator or study staff will discuss with each subject and the subject’s parent(s) 
or legal guardian(s) the nature and purpose of the study and the required study 
procedures.  The subject’s medical history and medication history will be reviewed to 
determine initial eligibility for participation in the study and the subject’s de-identified 
dystrophin genetic test report and/or muscle biopsy report will be sent to the Central 
Genetic Counselor(s) for confirmation that the subject meets the DMD diagnostic 
inclusion criteria.  Demographic information will be collected. 
Following the signing of the written ICF, subjects will be considered to be enrolled in the 
study and will be assigned a unique site-specific 6-digit subject ID number that will be 
comprised of protocol, site, and subject numbers in sequential order of screening into the 
study.  All data will be identified using the unique subject ID number.  The site 
Investigator will keep a record relating the names of the subjects to their subject ID 
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.  The Coordinating Center will not collect names or other 
identifiers except dates (diagnosis, study visits), age at enrollment, and the subject ID 
number. 
Subjects will undergo the procedures in the bulleted list below and in Table 2 during the 
Screening Period.  The procedures may be completed over the course of several visits, if 
necessary, but all scheduled Screening procedures must be completed within the 
timeframe of Day -33 to Day -2, and the actual date each procedure is performed must be 
recorded in the source document and eCRF.  Any parameter/test may be repeated at the 

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Investigator’s discretion during Pretreatment Screening to determine reproducibility.  In 
addition, subjects may be rescreened if ineligible due to negative anti-varicella IgG 
antibody test result. 
Subjects meeting all Screening eligibility tests will be assigned to treatment at the 
Baseline Day -1 Visit. 
x Enrollment (see Section 5.9) 
x Review of the Inclusion and Exclusion Criteria (see Sections 4.2 and 4.3) 
x Recording of the medical history, including any toxicities or allergy-related 
events to prior treatments (see Section 7.2.1) 
x Recording of prior medications (Medication History) (see Section 5.7.1) 
x Complete physical examination, including weight (in kilograms) and height (in 
cm) and assessment of cushingoid features (see Section 7.2.2) 
x Recording of vital signs (sitting blood pressure, heart rate, body temperature, 
respiratory rate) (see Section 7.2.3) 
x Collection of blood for clinical laboratory testing (hematology, clinical chemistry, 
lipids, and vitamin D) and collection of urine for urinalysis (see Section 7.2.4) 
x Collection of blood for HbA1c (see Section 7.2.6) 
x Confirmation of chicken pox immunity (see Section 7.2.5) 
x 12-lead ECG (see Section 7.2.9) 
x Eye exam (see Section 7.2.10) 
x Bayley-III Gross Motor scale (ages 2 to <4 years only) (see Section 7.3.1) 
x PUL Test (ages 7 to <18 years only) (see Section 7.3.2) 
x Pediatric Outcomes Data Collection Instrument questionnaire (PODCI) (see 
Section 7.4.1)  
x PARS III questionnaire (see Section 7.4.2) 

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x Recording of AEs and SAEs beginning at the time written informed consent is 
obtained (see Section 7.6) 
6.3.2. 
Baseline Period (Day -1) Visit 
Subjects who have met all study eligibility criteria will return to the study site during the 
Pretreatment Baseline Period (Day -1, the 24-hour interval immediately preceding 
administration of the first dose of study medication) for baseline assessments and will be 
assigned to treatment group by the TRiNDS Study Coordinator at the Baseline Day -1 
Visit.  Subjects will retain their 6-digit study identification number which was assigned 
during the Screening Period. 
The following procedures will be completed at the Baseline Day -1 Visit: 
x Physical examination including weight (in kilograms) and assessment of 
cushingoid features and ambulatory status (see Section 7.2.2)  
x Recording of vital signs (sitting blood pressure, heart rate, body temperature, 
respiratory rate) (see Section 7.2.3)  
x Bayley-III Gross Motor scale (ages 2 to <4 years only) (see Section 7.3.1)  
x PUL Test (ages 7 to <18 years only) (see Section 7.3.2) 
x Recording of AEs and SAEs; review of all AEs for resolution status and date 
(see Section 7.6) 
x Recording of prior medications (Medication History) (see Section 5.7.1) 
x Assignment (see Section 3.3) 
6.3.3. 
Treatment Period Day 1 Visit 
At the Treatment Period Day 1 Visit, certain procedures will be performed prior to 
administration of the first dose of study drug and are listed in this section.  Treatment 
Period Day 1, for purposes of the study analyses, begins with administration of the first 
dose of study medication.   

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Subjects will take the first dose of study medication in clinic on the day after the 
Pretreatment Baseline (Day -1) Visit. Breakfast will be served at the study site after the 
blood and urine collections for clinical laboratory tests and the blood draws for PD 
biomarkers, and within 30 minutes prior to administration of the dose of study 
medication.   
Subjects will receive a medical “alert” card stating that participation in the study may 
increase the subjects’ risk of adrenal suppression.  The card will include instructions for 
families and clinicians regarding management of possible adrenal suppression during 
emergencies, including coverage with “stress doses” of hydrocortisone (or prednisone) 
during times of illness, injury, or surgery. 
The following procedures will be completed at the Treatment Period Day 1 Visit: 
x Recording of vital signs (sitting blood pressure, heart rate, body temperature, 
respiratory rate) prior to administration of first dose of study drug (see 
Section 7.2.3)  
x Clinical laboratory evaluation including hematology, clinical chemistry, lipids, 
and urinalysis tests, prior to administration of first dose of study drug (see 
Section 7.2.4) 
x Blood samples for PD biomarkers including fasting glucose and insulin, 
osteocalcin, CTX, serum P1NP, and morning cortisol, prior to administration of 
first dose of study drug (see Section 7.2.6).  Blood remaining from collected 
samples not needed for protocol-specified analyses may be stored for future 
exploratory biomarker studies , including in the additional 12 to <18 years age 
group: suppression of the gonadal axis (LH, FSH) and suppression of the thyroid 
axis (TSH, FT4). 
x Blood samples for plasma PK, collected within 30 minutes prior to administration 
of first dose of study medication and at various time points post-dose (see 
Section 7.2.7) 

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x Dispensing of study medication and administration of first dose (see Section 5.8.1 
and Section 5.3, respectively) 
x Dispensing of subject diary (see Section 7.5) 
x Recording of AEs and SAEs; review of all AEs for resolution status and date 
(see Section 7.6) 
x Recording of concomitant medications (see Section 5.7) 
On Day 1, the subject will be discharged from the clinic after completion of all scheduled 
assessments.  
6.3.4. 
Treatment Period (Weeks 1-12) 
Subjects will return to the study site for safety, PK, clinical efficacy, PD, behavior and 
neuropsychology, and physical functioning assessments beginning at Week 2 and 
continuing through the Week 12 Visit, according to the schedule of assessments in 
Table 2. 
Subjects will continue to receive daily oral administration of vamorolone suspension 
according to their assigned treatment throughout the 12-week Treatment Period.  The 
daily dose of study medication should be taken with breakfast.Dosing is to occur at home 
throughout the 12-week Treatment Period, except at the Week 2, 6, and 12 study visits, 
when dosing will occur at the study site.  Subjects must have fasted ≥ 6 hours prior to 
arrival at the study site for the Weeks 2, 6, and 12 study visits.  Breakfast will be served 
at the study site after the blood collections for clinical laboratory tests (all visits) and 
Vitamin D (Week 12 only); pre-dose blood draw for plasma PK analysis (Week 2 only); 
and blood draws for PD biomarkers, including insulin, glucose, HbA1c, morning cortisol, 
osteocalcin, CTX, P1NP (Week 12 only); and within 30 minutes prior to administration 
of the dose of study medication.  Blood samples for plasma PK analysis will also be 
collected pre-dose and at several time points post-dose at the Week 2 Visit (see 
Section 7.2.7).  Ease of Administration of Study Medication Administration (ages 2 to 
<4 years) and Study Medication Acceptability (7 to <18 years) will be assessed at the 
Weeks 6 and 12 Visits.  Apart from blood and urine sample collections, all other 

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scheduled assessments should be performed after administration of the study medication 
in clinic.    
Study medication will be dispensed at Weeks 6 and 12 (for subjects participating in the 
Dose-tapering Period) Visits, and returned at Weeks 2 (compliance monitoring only; will 
be re-dispensed at end of visit), 6 and 12 for all subjects.  Subjects will receive subject 
diaries at each study visit beginning at Day 1 and return the diaries at each subsequent 
visit.  Diaries will be reviewed with the subject’s parent or guardian by the study staff to 
assess AEs, changes to concomitant medications/therapies, and any missed or incomplete 
doses of study medication.   
Safety assessments will be conducted at the Week 2 Visit. 
Clinical efficacy assessments (Bayley-III Gross Motor scale [ages 2 to <4 years] and 
PUL Test [ages 7 to <18 years]) and the subject reported outcomes (PARS III, PODCI, 
Ease of Study Medication Administration Assessment (ages 2 to <4 years), and Study 
Medication Acceptability Assessment (7 to <18 years) will be conducted as specified in 
the schedule of study activities.   
Weight will be recorded at every visit and height will be measured at the Week 12 Visit.  
Vital signs will be recorded at each study visit.  A physical examination including 
assessment of cushingoid features will be performed at Weeks 6 and 12.  A 12-lead ECG 
will be recorded at Week 12.  Blood and urine samples for clinical laboratory tests and 
blood for the serum PD biomarker panel will be collected at scheduled visits throughout 
the study (Table 2).  An eye examination to exclude cataracts and glaucoma will be 
performed at Week 12.  Adverse events, including SAEs, and concomitant medications 
will be assessed at each study visit and recorded throughout the study.  
The scheduled Week 12 assessments may be performed over a 2-day period, if necessary, 
to facilitate scheduling.  The scheduled 12-lead ECG, eye examination, PODCI, and 
PARS III may be completed on the day prior to the final Week 12 dose of study 
medication; alternatively, these assessments may be performed on the date of the final 
Week 12 dose of study medication.  The scheduled physical examination, weight, height, 
vital signs, clinical laboratory tests, blood draws for PD biomarker analysis, Ease of 

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Study Medication Administration Assessment (ages 2 to <4 years only)/Study 
Medication Acceptability Assessment (ages 7 to <18 years only), functional assessments 
(Bayley-III Gross Motor scale [ages 2 to <4 years] and PUL Test [ages 7 to <18 years]), 
recording of AEs/SAEs and concomitant medications, and return of subject diaries should 
be performed on the date of the final Week 12 dose of study medication.   
Subjects who complete the VBP15-006 study and will enroll directly into the expanded 
access or compassionate use program to continue vamorolone treatment or will transition 
directly onto SoC glucocorticoid treatment for DMD will be discharged from the 
VBP15-006 study following completion of all Week 12 assessments.  Subjects who will 
not continue vamorolone treatment in the expanded access or compassionate use 
program, and who will not transition directly to SoC glucocorticoid treatment for DMD, 
will have their vamorolone dose tapered prior to discharge from the study (see 
Section 6.3.5).  Site study staff will contact the parent(s)/guardian(s) by telephone at 
Week 14 to ensure that the dose tapering is proceeding according to protocol, to assess 
potential signs or symptoms of adrenal suppression, and to address any questions the 
parent(s)/guardian(s) may have. 
6.3.5. 
Dose-tapering Period (Weeks 13-16) 
All subjects who complete the study and opt not to continue directly with vamorolone 
treatment in an expanded access or compassionate use program, and who will not 
transition directly to SoC glucocorticoid treatment for DMD, will participate in a Dose 
tapering Period during which the dose of study medication will be progressively reduced.  
In addition, subjects who discontinue study medication after the first dose and prior to 
Week 12 will also participate in the Dose-tapering Period if possible and if, in the opinion 
of the Investigator, it is safe to do so.   
The purpose of dose-tapering is to aid in re-establishment of adrenal function if adrenal 
suppression has occurred during vamorolone treatment.  Dose tapering will be performed 
in a stepwise manner, according to the subject’s most recent calculated liquid formulation 
dose during the 12-week Treatment Period.  

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starting hydrocortisone, in the steroid-treated 7 to <18 years age group on 6 mg/kg/day at 
Week 12.  
Subjects will have non-fasting but morning blood and urine samples collected for clinical 
laboratory tests at the Week 16 Visit.  Subjects will also have a physical examination 
with weight, assessment of cushingoid features and vital signs recorded.  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.   
Subjects participating in the Dose-tapering Period will be discharged from the study 
following completion of all Dose-tapering Period assessments. 
6.4. 
Subject Discontinuation 
Any subject who chooses to withdraw from the study after Day 1 and prior to the 
Week 12 Visit should return to the study site for Week 12 assessments at the time of 
early withdrawal, whenever possible (see Section 6.3.4), assuming the subject has not 
withdrawn consent, and will participate in the Dose-tapering Period,. Site personnel will 
document and evaluate all assessments, including any AEs and lab results, in the source 
documents and eCRF.   
In the event that a subject withdraws early from the study prior to the Week 12 Visit, the 
reason for discontinuation must be fully documented in the source documents and the 
eCRF.   
In the event a subject withdraws informed consent, no further study procedures should be 
performed and no additional data should be collected.  Any data collected up to the point 
of withdrawal of consent may be used by the Sponsor.  Every effort will be made to 
ensure that subjects who withdraw consent undergo dose-tapering, as appropriate, prior to 
the date of withdrawal of consent.  Subjects who withdraw early from the study may be 
replaced, at the discretion of the Sponsor. 
Subjects who discontinue study medication should follow the procedures for dose 
tapering, as outlined in Section 6.3.5 and Table 3.   

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Subjects who discontinue early from the study will take the first dose of study medication 
in the Dose-tapering Period with a meal on the day after the last dose of Treatment Period 
study medication. 
Dose-tapering for subjects who discontinue the study early is to aid in re-establishment of 
adrenal function if adrenal suppression has occurred with vamorolone treatment.   
Subjects will be assessed promptly if unwell during the tapering phase or in the weeks 
following study medication cessation due to the risk of adrenal suppression.  There will 
be a low threshold for recommending commencement of daily oral prednisone or 
hydrocortisone, or intravenous hydrocortisone if hospitalization occurs in these 
circumstances. 
The final end-of-study visit will be scheduled approximately one week after the final 
dose tapering to 0 mg/kg subjects if it is more than 4 weeks after last treatment dose (i.e., 
Week 12 dose, if treatment was not discontinued)..    
Subjects will have non-fasting blood and urine samples collected for clinical laboratory 
tests at the final Early Termination.  Subjects will also have a physical examination with 
weight, assessment of cushingoid features and vital signs recorded.  Study medication 
will be returned for compliance monitoring.  Adverse events, including SAEs, lab results, 
and concomitant medications will be assessed and documented.  Subject diaries will be 
returned and reviewed with site staff.   
Subjects will be discharged from the study following final Early Termination/Week 16 
assessments. 
6.5. 
Subject and Study Completion 
A completed subject is defined as a subject who has completed the Treatment Period, 
through the Week 12 Visit assessments, and Dose-tapering Period, if applicable, and has 
not prematurely withdrawn from the study for any reason.  The study will be completed 
when the final subject has completed his final study visit (“last subject, last visit”). 

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7. 
STUDY ASSESSMENTS AND MEASUREMENTS 
7.1. 
Demographic Assessments 
Demographic information (age at enrollment, race and ethnicity; date of birth may also be 
collected where allowed) will be collected during the Pretreatment Screening Period and 
will be recorded on the appropriate eCRF page. 
7.2. 
Safety and Tolerability Assessments 
7.2.1. 
Medical History 
The medical history will be recorded at the Screening Visit and will include significant 
past medical or surgical procedures as well as previous and current co-existent diseases.  
It should include the date (month/year) the subject was diagnosed with DMD, initial 
symptoms of DMD and the age at which they were first identified, and any toxicities 
or allergies to prior treatments.  It should include relevant medical history for the 
following body systems: head, eyes, ears, nose and throat (HEENT), respiratory, 
cardiovascular, gastrointestinal, endocrine, hematological, dermatological, genital-
urinary, neurological, musculoskeletal, psychological/psychiatric, and any other history 
of medical significance.  The medical history will be recorded in the source document 
and on the appropriate eCRF page. 
7.2.2. 
Physical Examination, Cushingoid Features, Ambulatory status, Weight, 
and Height 
A complete physical examination will be performed at Screening, Baseline Day -1, 
Week 6, and Week 12, and at the final Dose-tapering Period Visit, 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.  Particular attention will 
be paid to any sign or symptom of infection. Clinically significant changes from baseline 
should be recorded as AEs.  Particular attention will be paid in identifying any sign of 
cushingoid features, which should also be recorded as AEs if they first appear or worsen 

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during the study. Ambulatory status as assessed by the investigator will be recorded at 
Baseline. 
Additional unscheduled symptom-directed physical examinations may be conducted at 
any time at the Investigator’s discretion.   
Height (in cm) will be recorded at Screening and Week 12.  Standing height will be 
recorded for subjects in the 2 to <4 years age group and all participants in the 7 to <18 
years age group who can stand independently.   
Weight (in kg) will be recorded at Screening, Baseline, Day -1, Week 2, Week 6, and 
Week 12, and at the final Week 16 Dose-tapering Visit. Weight recorded at the 
dispensing visit will be used to calculate the study medication dose for the subsequent 
dispensing interval (see Section 5.3).   
Results will be recorded in the source document and on the appropriate eCRF page. 
7.2.3. 
Vital Signs 
Vital signs (sitting blood pressure, heart rate, respiration rate, and body temperature) will 
be recorded at Screening, Baseline Day -1, Day 1 pre-dose, Week 2, Week 6, and 
Week 12, and at the final Dose-tapering Visit.  Vital signs should be recorded after the 
subject has been resting for at least 5 minutes.  Body temperature may be measured using 
oral, tympanic, or temporal recording devices; however, the same methodology must be 
used for all assessments of a given subject. 
Results will be recorded in the source document and on the appropriate eCRF page. 
If vital signs are recorded at the same study visit as blood collection and ECG recording, 
at least 15 minutes should elapse after collection of blood samples and before performing 
ECG and recording vital signs. 
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 4 and Table 5 below, during 
the Screening Period, at the Day 1, Week 6, Week 12, and Week 16 Visits. Blood for 

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vitamin D is collected at the Screening and Week 12 Visits only.  Fasted blood samples 
for clinical laboratory tests will be collected pre-dose at the Day 1, Week 2, Week 6, 
Week 12, and Week 16 Visits.  Urine samples may be collected non-fasting at all 
scheduled visits.  Details of blood and urine collections can be found in the Laboratory 
Manual. 
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.  A total of approximately 21 mL of blood will be 
collected over the course of this study for clinical safety laboratory evaluation, including 
measurement of vitamin D (see Section 7.2.8 for details of blood volumes to be 
collected).   
If blood collection is performed at the same study visit as vital signs assessment and ECG 
recording, at least 15 minutes should elapse after collection of blood samples and before 
performing ECG and recording vital signs. 
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: 
x Accompanied by clinical symptoms  
x 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)  
x 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 

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Protein 
WBC/hpf 
Glucose 
RBC/hpf  
Ketones 
Casts 
pH 
Bacteria 
Leukocyte esterase 
 
Blood 
 
a. A midstream clean-catch urine specimen will be collected for dipstick analysis.   
 
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 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, and followed-up until the results have returned to the normal range, 
stabilized, and/or an adequate explanation for the abnormality is found.  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 assessed 
(see Section 7.6). 
7.2.5. 
Chicken Pox Immunity 
Subjects must provide evidence of immunity to varicella zoster virus to be eligible for 
assignment to treatment.  Evidence of immunity may be determined by either a positive 
anti-varicella IgG antibody test result obtained during the Screening Period, or 
documentation, provided at the Screening Visit, that the subject has had 2 doses of 
varicella vaccine, with or without serologic immunity, with the second of the 2 doses 
given at least 14 days prior to assignment to a dose group.  For subjects whose anti-

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varicella antibody titer will be measured at Screening, a 2 mL blood sample will be 
collected for antibodies (IgG) to Varicella Zoster virus to confirm immunity.  The blood 
sample will be sent to the local laboratory for testing.  
If antibodies are not detected in the blood sample sent to the local laboratory, and 
documentation of two previous vaccinations against varicella cannot be provided, 
immunization before starting the trial will be advised and the immunization status must 
be re-checked prior to assignment to a dose group (see Manual of Operations for details).  
Lack of willingness to immunize a child who is not already immune to chicken pox will 
be a reason for exclusion of the child from the trial.  
7.2.6. 
Pharmacodynamic Biomarker Panel 
Blood samples will be collected to explore the effect of vamorolone on biomarkers 
associated with glucocorticoid safety concerns (exploratory outcomes for adrenal 
suppression, insulin resistance, and bone turnover, as well as, in the additional 12 to <18 
years age group, suppression of the gonadal axis (LH, FSH) and suppression of the 
thyroid axis (TSH, FT4)), as listed in Table 6. 
Blood samples will be collected pre-dose at the Day 1 and Week 12 Visits for analysis of 
biomarkers for exploratory outcome measures of adrenal suppression, bone turnover, and 
insulin resistance (HbA1c will be analyzed at Screening and Week 12).  Approximately 
6 mL of blood will be collected for the PD biomarker panel (fasting glucose and insulin 
[insulin resistance], morning cortisol [adrenal suppression], and osteocalcin, P1NP, and 
CTX [bone turnover] biomarkers) at each scheduled collection time point; HbA1c will be 
analyzed from the hematology sample .  Samples collected at the Day 1 and Week 12 
Visits will be collected after the subject has fasted for ≥ 6 hours and prior to 
administration of the daily dose of study medication; the sample collected at the 
Screening Visit for HbA1c measurement may be collected non-fasting.  Blood for 
morning cortisol measurement should be collected before 10 AM local time.   
Blood remaining from collected samples not needed for protocol-specified analyses at 
each of the blood collection time points may be stored for future exploratory biomarker 
studies for aspects of safety and efficacy.  These remaining blood samples may be 

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released for research purposes, including research on biomarkers in DMD.  Any released 
samples will have no identifying subject information.   
Additional HbA1c determination should be performed if urine glucose is positive and/or 
fasted glucose levels are above normal limits at any of the scheduled assessment time 
points (see Laboratory Manual).  
A total of approximately 19 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin, morning cortisol, osteocalcin, CTX, and P1NP, as well as, in 
the additional 12 to <18 years age group, LH, FSH, TSH, FT4) over the course of the 21-
week study (see Section 7.2.8).   
Table 6. 
Pharmacodynamic Biomarkers – Exploratory Safety Outcomes 
Adrenal Suppression 
Cortisol – morning 
Insulin Resistance 
Glucose – fasting 
Insulin – fasting 
HbA1c 
Bone Turnover 
Osteocalcin 
CTX 
P1NP 
Suppression of the gonadal axis 
LH 
FSH 
Suppression of the thyroid axis 
TSH 
FT4 
 
7.2.7. 
Pharmacokinetic Assessment 
At the Day 1 and Week 2 Visits, all subjects will have blood collected for PK 
assessments within 30 minutes prior to and at 1, 2, and 6 hours (ages 2 to <4 years), or 
within 30 minutes prior to and at 1, 2, 4, 6 and 8 hours (ages 7 to <18 years) following 

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administration of the daily dose of study medication.  Approximately 1.2 mL of blood 
will be collected into K2-EDTA tubes at each assessment time point (total of 
approximately 10 mL blood collected for PK assessment in 2 to < 4-year-old subjects and 
total of approximately 15 mL blood collected for PK assessments in ages 7 to <18 years).   
Plasma concentrations of vamorolone will be measured using a specific and validated 
liquid chromatography tandem mass spectrometry assay.  PK assessments will be 
performed by a central laboratory.  The procedures for the collection, handling, and 
shipping of laboratory samples will be specified in the Laboratory Manual(s) provided to 
the study sites. 
The exact time of vamorolone administration and blood sampling will be recorded in the 
source document and eCRF. 
If PK and PD or clinical laboratory blood samples are to be collected at the same time 
point, the PK blood sample should be collected in the order specified in the laboratory 
collection flow chart. 
7.2.8. 
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 up-to-21-week study are summarized in 
Table 7.  A total of approximately 51 mL of blood will be collected from each 2 to <4-
year-old subject, and appoximately 56 mL of blood will be collected from each 7 to <18-
year-old subject over the course of the up-to-21-week study. 

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Table 7. 
Blood Sample Number and Volume by Study Visit 
 
Blood Volume (mL) 
Test 
SCR 
Day 1 
Week 2 
Week 6 
Week 12 Week 16 
Total 
Volume 
Clinical Safety Labsa 
3.7b 
3.7b 
 
3.7b 
3.7b 
3.7b 
18.5 
Varicella Zoster IgG 
2 
 
 
 
 
 
2 
Vitamin D 
1.2 
 
 
 
1.2b 
 
2.4 
PD Biomarker Panelc 
 
9.2b 
 
 
9.2b 
 
18.4 
PKd 
Ages 2 to <4 years 
Ages 7 to <18 years 
 
 
4.8 
7.2 
 
4.8 
7.2 
 
 
 
 
9.6 
14.4 
Total Volume by Visit (mL) 
Ages 2 to <4 years 
Ages 7 to <18 years 
6.9 
 
17.7 
20.1 
 
4.8 
7.2 
3.7 
14.1 
3.7 
 
50.9 
55.7 
Total Volume: 50.9 mL (ages 2 to <4 year); 55.7 mL (ages 7 to <18 year) 
SCR = Screening 
a Hematology, Chemistry, Lipids, HbA1c 
b Subjects must have fasted ≥ 6 hours prior to blood draws. 
c Fasting glucose, insulin, morning cortisol, CTX, P1NP, osteocalcin; pre-dose on Day 1 and Week 12.   
d Blood drawn for population PK within 30 minutes pre-dose and at 1, 2, and 6 hours post-dose at the Day 1 
and Week 2 Visits (ages 2 to <4 years), or 30 minutes pre-dose and at 1, 2, 4, 6 and 8 hours post-dose at the 
Day 1 and Week 2 Visits (ages 7 to <18 years).  Subjects must be fasting at the time of collection of the 
Day 1 and Week 2 pre-dose samples. 
 
7.2.9. 
12-Lead ECG 
12-lead ECGs will be recorded at the Screening and Week 12 Visits.  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.  
If blood collection, vital signs assessment, and ECG recordings are scheduled at the same 
study visits, at least 15 minutes should elapse between collection of blood samples and 
before performing ECG and recording vital signs. 

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ECG results will be read locally.  Results must be interpreted.  ECG reports must be 
retained in the source document, and results recorded on the appropriate eCRF page. 
7.2.10. 
Eye Examination 
An eye examination will be performed by a certified and appropriately trained 
optometrist or ophthalmologist at Screening and Week 12 to assess for presence and 
degree of cataracts and glaucoma.  Number and severity of cataracts, if present, will be 
recorded.  Ocular pressure and presence/absence of glaucoma will be recorded. 
Results must be interpreted and recorded in the source document and on the appropriate 
eCRF page. 
7.3. 
Assessment of Muscle Function 
Muscle strength and function assessments should be performed in the morning and at 
approximately the same time of day, whenever possible. 
7.3.1. 
Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross 
Motor Scale 
The Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale 
will be assessed for subjects in the 2 to <4 years age group at the Screening, Baseline 
Day -1, and Week 12 Visits.  
The Bayley-III Gross Motor scale is comprised of 72 items that assess developmental 
functioning and include movement of the limbs and torso, static positioning (e.g., sitting, 
standing), dynamic movement including locomotion and coordination, balance, and 
motor planning [Connolly et al, 2019]. Complete instructions for administering and 
scoring the Bayley-III Gross Motor scale are given in the Clinical Evaluator Manual to be 
supplied to the sites prior to study start. 
Results will be recorded in the source document and in the eCRF. 

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7.3.2. 
Performance of Upper Limb (PUL) Test 
The Performance of Upper Limb (PUL) Test will be assessed at the Screening, Baseline 
Day -1, and Week 12 Visits.  
The PUL was developed specifically for DMD and is capable of assessing a wide-
spectrum of upper extremity function in both ambulant and non-ambulant individuals 
with DMD.  The PUL provides a total upper extremity functional score capable of 
characterizing overall progression and severity of disease, while its component subscores, 
which assess the 3 major level dimensions (shoulder-, middle-, and distal-levels), can 
track the stereotypical proximal-to-distal progressive loss of upper limb function in DMD 
[Pane et al, 2014]. Complete instructions for administering the PUL are given in the 
Clinical Evaluator Manual to be supplied to the sites prior to study start. 
Results will be recorded in the source document and in the eCRF. 
7.4. 
Patient-Reported Outcome Measures 
7.4.1. 
Pediatric Outcomes Data Collection Instrument (PODCI) 
Physical functioning will be assessed by completion of the Pediatric Outcomes Data 
Collection Instrument (PODCI).  The subject’s parent(s)/legal guardian(s) will be asked 
to complete this instrument at the Screening and Week 12 Visits.   
The completed Instrument is considered the source documentation for this assessment.  
Results will be recorded in the eCRF. 
7.4.2. 
Behavioral Assessment 
One instrument, for completion by the parent(s)/guardian(s), will be used for behavior 
assessment screening and evaluation of behavior change.  This is the PARS III, a scale 
designed to measure psychosocial adjustment of children with chronic physical illnesses.  
The PARS III will be completed by the parent(s)/guardian(s) at the Screening and 
Week 12 Visits.  The PARS III is available in all primary languages spoken at sites for 
this study. 

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The completed assessment is considered the source documentation.  Results will be 
recorded in the eCRF. 
7.4.3. 
Ease of Study Medication Administration Assessment 
Ease of administration of the study medication will be assessed by the 
parent(s)/guardian(s) for subjects in the 2 to <4 years age group at the Weeks 6 and 12 
Visits.  Results will be recorded in the source document and eCRF. 
7.4.4. 
Study Medication Acceptability Assessment 
Acceptability of the study medication will be assessed by subjects in the 7 to <18 years 
age group using a 5-point hedonic scale immediately before (smell) and after (taste) 
dosing at the Week 6 and Week 12 Visits.  The assessments will be administered by 
trained study staff.  Results will be recorded in the source document and eCRF.  
7.5. 
Subject Diary 
The parent(s) or legal guardian(s) of each subject will be given a subject diary at the 
Day 1 Visit in which to record any new concomitant medications and any changes to 
existing concomitant medications taken during the study, any AEs experienced by the 
subject during the study, and any missed or incomplete doses of study medication.  
Parent(s)/legal guardian(s) 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 visit for use 
through the time of the next scheduled visit.  Collection of final diaries will occur at the 
end of the Dose-tapering Period, or at discharge from the study.   
7.6. 
Adverse Events and Serious Adverse Events 
An AE is any untoward medical occurrence in a subject and 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 

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product, whether or not considered related to the drug.  Pre-existing conditions that 
worsen during a study are to be reported as AEs. 
Signs and symptoms of DMD should not be recorded as AEs, unless their nature or 
severity is unexpected for the course of the disease. 
The Investigator is responsible for reporting AEs and SAEs to the Sponsor or designee.  
For reported death of a participant, the Investigator shall supply the Sponsor and the 
IRB/IEC with any additional information requested. 
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.  In 
addition, subjects (and their parent[s] or legal guardian ([s]) 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 
document 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 page.  The details recorded shall 
include the nature, date of onset, final outcome and its date, seriousness,intensity 
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).  The intensity of all AEs will be graded by CTCAE, Version 5.0.  Details of 
any medications given to the subject to abate the AE should be recorded on the 
appropriate eCRF page. 
7.6.1. 
Intensity 
All 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 CTCAE, version 5.0, 5-point 

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scale, and reported in detail as indicated in 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. 
7.6.2. 
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): 
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 

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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 do not meet the criteria for study drug relationship listed under remote, 
possible, or probable. 
7.6.3. 
Clinical Laboratory Test Abnormalities 
Clinical laboratory test results will be recorded on the designated eCRF page.  The 
intensity of abnormal clinical laboratory test results that are AEs will also be graded 

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using current FDA and the Council for International Organizations of Medical Sciences 
(CIOMS) drug-induced liver injury (DILI) guidance and the most current version of the 
CTCAE, version 5.0, 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: 
x Accompanied by clinical symptoms 
x 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) 
x 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. 
7.6.4. 
Follow-Up of Adverse Events 
Adverse events will be followed until they have returned to baseline status, stabilized, or 
the Investigator 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 document and 

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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 further follow-up of AEs will be 
documented in the source document and CRF.  
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. 
7.6.5. 
Dosing Error 
For the purposes of this study, a dosing error is defined as a dose exceeding or less than 
the scheduled dose of vamorolone suspension.  Such occurrences will be reported and 
recorded in the dosing page of the eCRF and as follows: 
x Use of study medication in doses in excess of that specified in the protocol will 
not be recorded as an AE unless there are associated signs or symptoms. 
x A dosing error with associated non-serious AEs will be recorded as AEs on the 
relevant AE forms in the eCRF. 
x A dosing error with an associated SAE will be recorded as an SAE. 
x Details of all dosing errors, including actual dose administered, will be 
documented in the source document and recorded in the appropriate 
documentation. 
7.6.6. 
Serious Adverse Events 
Serious adverse events (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.  For subjects who do 
not continue to receive vamorolone in an expanded access or compassionate use program, 

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site staff will make a phone call to the home 31-35 days after the final dose of study 
medication in the VBP15-006 study to confirm the final SAE status of the subject. 
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.  All SAEs, both related and unrelated, that begin within 
30 days after the subject’s final dose of study medication will be reported to the Sponsor 
within 24 hours of discovery by the Investigator.   
During the SAE collection period, the Investigator or clinical site personnel should notify 
the Coordinating Center of all SAEs, regardless of relationship to the investigational 
drug, within 24 hours of clinical staff becoming aware of the event; notification to the 
Coordinating Center will trigger alerts to the Sponsor. The Investigator will provide the 
initial notification by completing the SAE Report Form in the electronic data capture 
(EDC) system, which must include the Investigator’s assessment of the relationship of 
the event to investigational drug, and must be signed by the Investigator. 
In addition, notification is sent by the Investigator to the IRB/IEC and the subject’s 
Primary Care Physician. 
Follow-up information, or new information regarding an ongoing SAE, must be provided 
promptly to the Coordinating Center within 24 hours of knowledge of the new or 
follow-up information, which will forward the information to , the Sponsor. 
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: 
x Is fatal (results in the outcome of death) 
x Is life-threatening  
x Requires in-patient hospitalization or prolongation of existing hospitalization 
x Results in persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions 

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x Is a congenital anomaly or birth defect 
x 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 terms death and sudden death are clearly distinct and must not be used 
interchangeably. 
Any AE (including treatment-emergent, clinically significant, abnormal laboratory test 
values), 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 Sponsor 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 
Coordinating Center, who will notify the Sponsor within 24 hours of the Investigator 
becoming aware of the new information. 
All 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.  All SAEs, related and 
unrelated, must be reported to the Sponsor within 24 hours of first awareness. 
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 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 ICON safety 
management team within 24 hours, using the contact information below:  
In United States and Canada: 
 
Email: CHOSafety@iconplc.com 
 
Drug Safety Fax: 1 888 772 6919 or 1 434 951 3482 
 
SAE Questions: Drug Safety Helpline: 1 800 772 2215  
In Europe, Asia, Pacific, Africa and Australia: 

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Email: MHGSafety@iconplc.com 
 
Drug Safety Fax: +44 1792 525720 
 
SAE Questions: Drug Safety Helpline: +49 621 878 2154 
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. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) Identification and Reporting 
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is a suspected adverse 
reaction that is both serious and unexpected (not identified in the Investigator’s 
Brochure).  Sponsor will inform Investigators of SUSARs in a manner and timeframe 
consistent with applicable national regulatory requirements. 
The study will comply with all local regulatory requirements.  This study adheres to the 
definition and reporting requirements of ICH Guideline for Clinical Safety Data 
Management, Definitions and Standards for Expedited Reporting. 

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8. 
STUDY COMMITTEES 
Data and Safety Monitoring Board 
A 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, propriety, 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: 
x 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; 
x Reviewing important protocol deviations; 
x Providing expert advice to the Sponsor on an ad hoc basis regarding matters such 
as safety concerns or diagnostic evaluations in individual subjects; 
x Based on the results of its deliberations, the DSMB can recommend continuation 
of the study unchanged, study interruption, study termination, modification of the 
study, or alteration in the DSMB monitoring plan. 

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9. 
DATA COLLECTION 
9.1. 
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, 
and/or x-rays.  Data collected during this study must be recorded in the appropriate 
source documents. 
Investigators 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. 
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 dates of enrollment and 
completion/termination, and the reason the subject was not entered (if applicable).   
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. 
9.2. 
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 its Enterprise version used in this study is 21 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 usernames and 

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passwords should never be shared and their electronic signature constitutes the legally 
binding equivalent of a handwritten signature.  Only trained personnel certified by the 
Coordinating Center will receive a username 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).   
The Coordinating Center data management team will monitor the eCRFs for 
completeness and acceptability throughout the course of the study.  Santhera personnel 
(or their representatives) will be allowed read-only access to all source documents in 
order to verify eCRF entries. 
9.3. 
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 with the data management plan and will be available for 
statistical analysis according to the methods outlined in Section 10.7 and the Statistical 
Analysis Plan (SAP).  
9.4. 
Subject Diaries 
The information recorded in the diary will be considered source documentation, and any 
relevant requested information recorded in the diary should be transcribed by study staff 
to the appropriate eCRF page. 

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10. 
STATISTICAL METHODS AND PLANNED ANALYSES 
10.1. 
Sample Size Determination 
This is an open-label, parallel group, multiple dose study.  Study medication is 
administered daily in this Phase II trial.   
For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a total of 
approximately 20 subjects in the 2 to <4 years age group will be enrolled with 
approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day).  A 
total of approximately 34 subjects in the 7 to <18 years age group will be enrolled with 
approximately 12 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day) and 
each dose level group stratified 1:1 by glucocorticoid treatment status at study entry to 
include approximately 6 glucocorticoid-untreated subjects and 6 glucocorticoid-treated 
subjects at study entry, plus 10 subjects for the additional 12 to <18 years age group [6.0 
mg/kg/day - glucocorticoid-treated].  This sample size is considered sufficient to detect 
drug safety concerns in a pediatric population ages 2 to <4 and 7 to <18 years with DMD 
based on clinical judgment and prior study of vamorolone at these doses. The 
10 additional 12 to <18 years subjects will further ensure that the full age range is 
included. In addition, this sample size is sufficiently large to determine PK parameters.   
A drop-out rate is not considered; subjects who withdraw early from the study may be 
replaced. 
10.2. 
Statistical and Analytical Plan (SAP) 
The sections below summarize the intended statistical methods and analyses for this 
study.  A more detailed SAP will be written and finalized prior to any lock of the study 
database (final or interim, if applicable) and any analysis performed.  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.   
10.2.1. 
Deviations from the Statistical Analysis Plan 
Any deviation(s) from the original SAP will be described and justified in the clinical 
study report. 

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10.3. 
Analysis Populations 
Three populations will be defined for data analysis: Safety Population, modified Intent-
to-Treat (mITT) Population, and the Pharmacokinetic Population.   
10.3.1. 
Safety Population  
All subjects who receive at least one dose of study medication will be included in the 
Safety Population.  The Safety Population is the primary analysis population for safety 
and PD assessments.  Results will be presented “as treated.” 
10.3.2. 
Modified Intent-to-Treat (mITT) Population  
All subjects who receive at least one dose of study medication and have at least one post-
baseline assessment will be included in the mITT Population.  The mITT Population is 
the primary analysis population for clinical efficacy.  Subjects who receive at least one 
dose of study medication but never have post-baseline assessments will be excluded.  
Results will be presented “as randomized.” 
10.3.3. 
Pharmacokinetic (PK) Population 
All subjects who receive at least one dose of vamorolone study medication and have 
sufficient data for PK analysis will be included in the PK Population. 
10.4. 
Measures Taken to Avoid/Minimize Bias 
Not applicable. 
10.5. 
Interim Analysis 
No formal interim statistical analyses are planned, apart from the interim data views and 
presentations to be created for the DSMB .   
10.6. 
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 

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outcomes will be treated as missing, unless stated otherwise.  Full details are presented in 
the SAP. 
10.7. 
Statistical Analysis 
10.7.1. 
General Considerations 
Statistical analyses will be performed using SAS® version 9.4 or later. 
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.  Baseline measurement is defined as the last non-missing value prior to 
the first dose of study drug in the study.  
10.7.2. 
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 and listed. 
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 dose level within age group, and overall.  In addition, tables will be 
presented according to glucocorticoid status at study entry (ages 7 to <18 years only).  
Baseline characteristics presented in these summary tables will be reviewed for any 
clinically relevant differences among the treatment groups or age stratification groups, 
and may be accounted for in the statistical models for the endpoints. 
10.7.3. 
Safety and Tolerability Analyses 
The Safety Population will be used for presentations and analyses of the safety 
parameters.  Analyses will be done as per actual treatment received.  

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In general, all evaluations of clinical safety will be listed and presented using descriptive 
statistics by age group, dose level, and time point.  In addition, individual subject listings 
of all safety data will be created and sorted by age, dose level, and time point, and will be 
reviewed for any evidence of dose-related differences or trends in the safety profile of 
vamorolone.  Where considered relevant, plots will be created. 
Safety data will include BMI, weight, height, vital signs, eye examination results, and 
ECG results, and these will be presented using descriptive statistics. The BMI and height 
values will be evaluated both on the original scale and as z-scores. Safety laboratory data 
will be summarized using descriptive statistics, and out-of-range values will be listed.   
Furthermore, continuous safety endpoints will be evaluated using a Mixed Model for 
Repeated Measures (MMRM), when appropriate. The models will include the baseline 
value as a covariate and visit, dose level, glucocorticoid use (when appropriate) and the 
relevant interaction terms as fixed effects. Separate models will be used for each age 
group. In case of no repeated measures (endpoint is assessed at one post-baseline visit 
only), Analysis of Covariance (ANCOVA) models will be used instead of MMRM. 
Adverse events will be summarized overall and by age group, dose level, glucocorticoid 
treatment at entry (7 to <18 years only), SOC, and preferred term (using the Medical 
Dictionary for Regulatory Activities [MedDRA]. Further analyses will be conducted by 
seriousness, severity and relationship to study medication. Adverse events leading to 
premature discontinuation of the study will be evaluated separately.  
Physical examination results will be listed only.   
10.7.4. 
Pharmacokinetic Analyses 
The pre-dose and post-dose plasma concentration measurements of vamorolone at Day 1 
and Week 2 will be used for comparison of drug exposures by age group, dose level, and 
glucocorticoid treatment at entry (ages 7 to <18 years only).  They will be aggregated 
with PK data from previous studies in DMD boys for comparison across the entire 
pediatric age range and with measurements obtained in healthy adult male subjects.  All 
PK data will be combined in a population assessment of plasma concentrations in relation 

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to age group, dose level, and glucocorticoid treatment at entry (ages 7 to <18 years only), 
as applicable. 
A separate population PK Analysis Plan will be created to further describe these analyses. 
10.7.5. 
Pharmacodynamic Analyses 
The evaluations of PD biomarkers will be performed using the Safety Population. 
Analyses will be done as per treatment actually received. 
All PD biomarker results will be summarized and listed.  
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone turnover, 
as well as exploratory biomarkers of safety and efficacy (including in the additional 12 to 
<18 years age group: suppression of the gonadal axis (LH, FSH) and suppression of the 
thyroid axis (TSH, FT4)) will be assessed.  Standard descriptive statistics will be used to 
summarize PD biomarkers by dose level within age group. Change from baseline will be 
presented.  For subjects 7 to <18 years of age, descriptive statistics will be presented 
separately for those subjects who were on SoC glucocorticoid therapy at the time of 
assignment to a dose group and those subjects who had been off SoC glucocorticoid 
therapy for at least 3 months at the time of assignment.  
The changes in serum PD biomarkers will be compared to the corresponding data if 
available collected in a previously conducted vamorolone study VBP15-004. The 
changes from baseline to week 12 in the present study (by dose level and age group) will 
be compared to the changes from baseline to week 12 in the four treatment groups of 
study VBP15-004 (vamorolone 2.0 mg/kg, vamorolone 6.0 mg/kg, placebo and 
prednisone 0.75 mg/kg). Furthermore, the differences between the groups will be 
evaluated with ANCOVA models including baseline value as a covariate and the 
treatment/age group as a fixed factor. Additional analyses will be conducted by 
glucocorticoid use group, when appropriate.   
Full details will be provided in the SAP. 

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10.7.6. 
Clinical Efficacy Analyses  
The evaluations of clinical efficacy will be performed using the mITT Population.  
Analyses will be performed as per treatment. 
All efficacy data will be summarized and listed.  Where considered relevant, plots will be 
created. 
The exploratory efficacy outcomes are the Bayley-III Gross Motor scale (2 to <4 years 
age group) and PUL Test (7 to <18 years age group).  Standard descriptive statistics will 
be used to summarize the clinical efficacy endpoints by dose level within age group. 
Change from baseline will be presented.  Within each age group, pairwise comparisons 
will be made to compare change from baseline for the vamorolone 6.0 mg/kg/day dose 
level group vs. the vamorolone 2.0 mg/kg/day dose level group.  For subjects 7 to <18 
years of age, descriptive statistics will be presented separately for those subjects who 
were on SoC glucocorticoid therapy at the time of assignment to a dose group and those 
subjects who had been off SoC glucocorticoid therapy for at least 3 months at the time of 
assignment.   
Furthermore, the changes from baseline to week 12 in the efficacy outcomes will be 
compared using ANCOVA models, including baseline value as a covariate and dose level 
and glucocorticoid use status (when appropriate) and the relevant interaction terms as 
fixed factors. Separate models will be used for each age group. 
Full details will be provided in the SAP 
10.7.7. 
Patient-Reported Outcome Analyses 
Patient-reported Outcomes including the PODCI, PARS III, Ease of Study Medication 
Administration Assessment, and the Study Medication Acceptability Assessment will be 
listed and presented using descriptive statistics by age group, dose level, and time point.  
For subjects 7 to <18 years of age, descriptive statistics for change from baseline 
assessments (PODCI and PARS III) will be presented separately for those subjects who 
were on SoC glucocorticoid therapy at the time of assignment to a dose group and those 

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subjects who had been off SoC glucocorticoid therapy for at least 3 months at the time of 
assignment. 
Full details will be provided in the SAP. 
10.7.8. 
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 .  All concomitant medications 
will be detailed in the subject data listings.   

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11. 
STUDY MANAGEMENT AND ETHICAL AND 
REGULATORY REQUIREMENTS 
11.1. 
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 and ICH E6 Guideline for Good Clinical 
Practice (GCP). 
Further, the trial will be conducted in accordance with all applicable laws, guidances and 
directives of the jurisdiction where the study is being conducted 
11.2. 
Investigator Responsibilities 
11.2.1. 
Subject Information and Informed Consent 
It is the Investigator’s responsibility to ensure that parent(s)/guardian(s) give(s) informed 
consent before the subject is admitted to the study, in accordance with ICH guidelines on 
GCP and all applicable laws, guidances and directives of the jurisdiction where the study 
is being conducted. 
If applicable, 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 written in a language they 
understand. 
The Investigator or designee will review the study with the parent(s)/guardian(s) 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(s)/guardian(s) of the subject.  The 
Investigator or designee and the parent(s)/guardian(s) of the subject must both sign and 
date the ICF after review and before the subject can participate in the study.  The 
parent(s)/guardian(s) of the subject will receive a copy of the signed and dated form, and 

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the original will be retained in the site study files.  The Investigator or designee must 
emphasize to the parent(s)/guardian(s) 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. 
11.2.2. 
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 relevant 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, 
as per ICH guidelines on GCP and all applicable laws, guidances and directives of the 
jurisdiction where the study is being conducted.  The Investigator will also keep 
documentation of study approval by internal committees per institutional requirements.  
It is the responsibility of the Sponsor to notify the competent authority of the Member 
State concerned and/or the IEC of any substantial amendment(s) to the protocol. 
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 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 

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approval, except when required to eliminate apparent immediate hazards to the subjects.  
In cases where any implemented deviation from, or a change of, the protocol to eliminate 
an immediate hazard(s) to trial participants is implemented without prior IRB/IEC 
approval, the implemented deviation should be notified as soon as possible not only to 
the IRB/IEC for review and approval/favorable opinion but also to the regulatory 
authority(ies). 
While the study is ongoing and at study completion/discontinuation, the Investigator must 
submit to the IRB/IEC the following information in accordance with applicable 
regulatory requirements where the study is being conducted: 
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. 
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. 
11.2.3. 
Study Documentation 
11.2.3.1. 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: 
x Fully signed protocol and protocol-supporting manuals 
x Investigator’s Brochure 
x Investigator Protocol Agreement form signed by the Investigator 
x IRB/IEC-approved copy of the ICF 

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x Curriculum vitae of the Investigator and all sub-investigators  
x A letter of IRB/IEC approval for protocol 
x A list of members of the IRB/IEC and their affiliations 
x A copy of the Investigator-signed FDA 1572 form 
x An Investigator-signed financial disclosure form 
x Investigator/site study contract. 
11.2.3.2. During the Study 
The following documentation should be added to the site study file during study conduct: 
x Any paper or electronic 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 
x Any changes to the documentation identified above (see Before the Start of the 
Study) 
x Shipping documents relating to shipment of medication (drug accountability) and 
bioanalytical samples 
x Copies of relevant correspondence such as letters, emails, meeting notes, and 
telephone calls. 
11.2.3.3. 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: 
x Study drug accountability documents 
x Audit certificates (if applicable) 
x Investigator delegation of responsibilities log 
x Site signature log 

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x Subject enrollment log 
x Subject identification log 
x Substantive correspondence with the Sponsor and IRB/IEC 
x Notification of the end of the trial to the IRB/IEC. 
11.2.4. 
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. 
11.3. 
Protocol Deviations  
11.3.1. 
Protocol Deviation Definitions 
Protocol deviations should be documented in accordance with the Manual of Operations. 
11.3.1.1. Protocol Deviation 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that 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. 
11.3.1.2. Important Protocol Deviation 
An important protocol deviation is a deviation from the IRB/IEC-approved protocol that 
may significantly 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. 

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11.3.2. 
Reporting Important Protocol Deviations 
Upon discovery of an important protocol deviation, the Investigator is responsible for 
reporting the important protocol deviation to the IRB/IEC and Sponsor or designee 
(Coordinating Center) within 24 hours of discovery, or according to local site 
requirements. 
All deviations must be recorded in the CTMS. 
11.4. 
Study Records Retention and Direct Access to Source Documents 
Following completion of the clinical study, the medical files of trial subjects as well as 
other essential documents shall be retained by the Sponsor and the Investigator for at 
least 10 years after completion of the clinical trial, or for a period of time as required by 
the applicable regulatory authority. 
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 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. 
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 identification log 
3. Subject enrollment log 
4. Record of all relevant communications between the Investigator and the IRB/IEC 
5. Composition of the IRB/IEC 

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6. Record of all relevant communications between the Investigator and the Sponsor 
(or designee) 
7. 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 
8. Drug accountability records (See Section 5.8.4) 
9. Record of any body fluids or tissue samples retained 
10. All other source documents (subject records, hospital records, laboratory records, 
etc.) 
11. All other documents as listed in Section 8 of the ICH consolidated guideline on 
GCP (Essential Documents for the Conduct of a Clinical Trial). 
11.5. 
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. 
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 
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) 

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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 11.7. 
11.6. 
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 
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. 

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11.7. 
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. 
11.8. 
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  
2. Failure of the Investigator to comply with applicable laws and/or pertinent 
regulations 
3. Submission of knowingly false information from the research facility to the 
Sponsor, Study Monitor, or regulatory authorities 

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4. Insufficient adherence to protocol requirements. 
If participation of a study site is terminated, the Sponsor 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 relevant 
regulations where the study is being conducted.  
11.9. 
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. 

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12. 
DISCLOSURE OF DATA 
12.1. 
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.  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, age at enrolment and birth date (may be collected where allowed by 
local regulations) 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 redacted 
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 information made available for 
inspection will be handled in the strictest confidence and in accordance with all 
applicable data protection / privacy laws in the relevant countries. 
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. 

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The study Investigator will maintain a subject identification log (enrollment numbers and 
corresponding subject names) to enable records to be identified. 
12.2. 
Publication 
Santhera Pharmaceuticals (Switzerland)  Ltd 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 Health 
Authorities of any country. 
Furthermore, in the event that the clinical research leads to patentable results, the 
Investigator (or entity acting on his/her behalf according to local requirements) shall 
refrain from filing patent application(s).  Patent applications will be filed by Santhera 
Pharmaceuticals (Switzerland) Ltd or another entity delegated by Santhera 
Pharmaceuticals (Switzerland) Ltd 
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 

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of the Sponsor.  Additionally, the Sponsor, may, for any reason, withhold approval for 
publication or presentation. 

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13. 
INVESTIGATOR PROTOCOL AGREEMENT 
The Investigator Protocol Agreement at the front of this document must be signed by the 
study site Principal Investigator.  The Investigator must retain the original and an 
electronic signed copy must be kept on file by the Sponsor.  The completed Protocol 
Agreement signifies review and acceptance of the protocol amendment by the Principal 
Investigator prior to initiation of the study. 
 

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14. 
REFERENCES 
Acharyya S, Villalta SA, Bakkar N, et al. Interplay of IKK/NF-kappa B signaling in 
macrophages and myofibers promotes muscle cell degeneration in Duchenne muscular 
dystrophy. J Clin Invest. 2007; 117(4): 889-901. 
Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, 
Cnaan A, McDonald CM; CINRG Investigators. Prednisone/prednisolone and deflazacort 
regimens in the CINRG Duchenne Natural History Study. Neurology. 2015; 85: 1048-55. 
Birnkrant DJ, Bushby K, Bann CM, et al; DMD Care Considerations Working Group. 
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and 
neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional 
management. Lancet Neurol. 2018; 17(3): 251-67. Erratum in: Lancet Neurol. 2018 
Apr 4.  
Birnkrant DJ, Bushby K, Bann CM, et al; DMD Care Considerations Working Group. 
Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, 
bone health, and orthopaedic management. Lancet Neurol. 2018; 17(4):347-61.  
Birnkrant DJ, Bushby K, Bann CM, et al; DMD Care Considerations Working Group. 
Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, 
emergency management, psychosocial care, and transitions of care across the lifespan. 
Lancet Neurol. 2018; 17(5): 445-55. 
Bowden SA, Connolly AM, Kinnettc K, Zeitler PS. Management of adrenal insufficiency 
risk after long-term systemic glucocorticoid therapy in Duchenne muscular dystrophy: 
Clinical Practice Recommendations Journal of Neuromuscular Diseases 2019: 6: 31–41.  
Buckon CE, Sienko SE, Fowler EG, et al. A longitudinal study of quantitative muscle 
strength and functional motor ability in ambulatory boys with Duchenne muscular 
dystrophy. J Neuromuscul Dis. 2022; 9(2): 321-34. 
Chen P, Satterwhite JH, Licata AA, et al. Early changes in biochemical markers of bone 
formation  predict  BMD  response  to  teriparatide  in  postmenopausal  women  with  
osteoporosis. J Bone Miner Res 2005; 20: 962–70. 
Ciafaloni E, Kumar A, Liu K, et al. Age at onset of first signs or symptoms predicts age 
at loss of ambulation in Duchenne and Becker muscular dystrophy: Data from the MD 
STARnet. J Pediatr Rehabil Med. 2016; 9(1): 5-11.  
Connolly AM, Zaidman CM, Golumbek PT, et al. Twice-weekly glucocorticosteroids in 
infants and young boys with Duchenne muscular dystrophy. Muscle Nerve. 2019; 59(6): 
650-57.  
Cooper MS, Blumsohn A, Goddard PE, et al. 11beta-hydroxysteroid dehydrogenase type 
1 activity predicts the effects of glucocorticoids on bone. J Clin Endocrinol Metab. 2003; 
88(8): 3874-7.  
Dogra C, Changotra H, Wergedal JE, Kumar A. Regulation of phosphatidylinositol 3-
kinase (PI3K)/Akt and nuclear factor-kappa B signaling pathways in dystrophin-deficient 
skeletal muscle in response to mechanical stretch. J Cell Physiol. 2006; 208(3): 575-85. 

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Evans NP, Misyak SA, Robertson JL, et al. Immune-mediated mechanisms potentially 
regulate the disease time-course of Duchenne muscular dystrophy and provide targets for 
therapeutic intervention. PMR. 2009; 1(8): 755-68. 
FDA Draft Guidance for Industry: Duchenne muscular dystrophy and related 
dystrophinopathies: developing drugs for treatment. June 2015. 
Fenton C, Martin C, Jones R, et al. Local steroid activation is a critical mediator of the 
anti-inflammatory actions of therapeutic glucocorticoids Annals of the Rheumatic 
Diseases 2021; 80: 250-60.  
Fenton CG, Doig CL, Fareed S, et al. 11β-HSD1 plays a critical role in trabecular bone 
loss associated with systemic glucocorticoid therapy. Arthritis Res Ther. 2019; 21(1):18. 
Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: 
Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline 
Development Subcommittee of the American Academy of Neurology. Neurology. 
2016;86(5):465-72.  
Griggs RC, Herr BE, Reha A, et al. Corticosteroids in Duchenne muscular dystrophy: 
major variations in practice. Muscle Nerve. 2013; 48(1): 27-31. 
Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the 
Duchenne muscular dystrophy locus. Cell. 1987; 51(6): 919-28. 
Howard ZM, Gomatam CK, Rabolli CP, et al. Mineralocorticoid receptor antagonists and 
glucocorticoids differentially affect skeletal muscle inflammation and pathology in 
muscular dystrophy. JCI Insight. 2022; 7(19): e159875.  
Kauh E, Mixson L, Malice MP, et al. Prednisone affects inflammation, glucose tolerance, 
and bone turnover within hours of treatment in healthy individuals. Eur J Endocrinol. 
2012; 166(3): 459-67. 
Koenig M, Hoffman EP, Bertelson CJ, et al. Complete cloning of the Duchenne muscular 
dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in 
normal and affected individuals. Cell 1987; 50: 509-17.  
Kumar A, Boriek AM. Mechanical stress activates the nuclear factor-kappaB pathway in 
skeletal muscle fibers: a possible role in Duchenne muscular dystrophy. FASEB J. 2003; 
17(3): 386-96. 
Mah JK, Korngut L, Dykeman J, et al. A systematic review and meta-analysis on the 
epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 
2014;24(6): 482-91.  
Malik V, Rodino-Klapac LR, Mendell JR. Emerging drugs for Duchenne muscular 
dystrophy. Expert Opin Emerg Drugs. 2012; 17(2): 261-77. 
McMillan HJ.  Intermittent glucocorticoid regimes for younger boys with duchenne 
muscular dystrophy: Balancing efficacy with side effects. Muscle Nerve. 2019 Jun; 
59(6): 638-9 

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Merlini L, Gennari M, Malaspina E, et al. Early corticosteroid treatment in 4 Duchenne 
muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012; 45(6): 796-802.  
Morgan SA, McCabe EL, Gathercole LL, et al. 11β-HSD1 is the major regulator of the 
tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci USA. 
2014; 111(24): E2482-91. 
Pahl HL. Activators and target genes of Rel/NF-kappa B transcription factors. Oncogene. 
1999; 18(49): 6853-66. 
Pane M, Mazzone ES, Sivo S, et al. Long term natural history data in ambulant Boys with 
Duchenne muscular dystrophy: 36-month changes. PlosOne. 2014; 10: 
1371/journal.pone.0108205. 
Rodriguez-Gonzalez M, Lubian-Gutierrez M, Cascales-Poyatos HM, et al. Role of the 
Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy. Int J 
Mol Sci. 2020; 22(1): 356. 
Schakman O, Kalista S, Barbé C, et al. Glucocorticoid-induced skeletal muscle atrophy. 
Int J Biochem Cell Biol. 2013; 45(10): 2163-72. 
Webster.JM, Sagmeister MS, Fenton CG, et al. Global Deletion of 11β-HSD1 prevents 
muscle wasting associated with glucocorticoid therapy in polyarthritis. Int J Mol Sci. 
2021; 22(15): 7828-40. 
 

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15. 
APPENDICES 
15.1. 
Vamorolone Dose Calculation Worksheet and Bulk Dispensing Guide 
15.1.1. 
Dose Calculation Worksheet 
Vamorolone is administered once daily as a 4.0% 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), 0.2 mL 
(5 mL syringe), or 0.2 mL (10 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 2.0 mg/kg/day with a body 
weight of 23 kg:  
Subject Weight (23 kg) x Dose Level (2.0 mg/kg) 
= 1.15 mL 
40 mg/mL 
The subject will receive a daily dose volume of 1.15 mL per dose throughout the period until 
the next scheduled study medication dispensing visit.  Dose will be administered using a 5 mL 
volumetric syringe rounded to the nearest 0.2 mL; i.e., 1.2 mL daily. 
 
Example 2: Dose volume calculation for a subject receiving 6.0 mg/kg/day with a body 
weight of 15 kg:  
Subject Weight (15 kg) x Dose Level (6.0 mg/kg) 
= 2.25 mL 
40 mg/mL 
The subject will receive a daily dose volume of 2.25 mL per dose throughout the period until 
the next scheduled study medication dispensing visit.  Dose will be administered using a 
10 mL volumetric syringe rounded to the nearest 0.2 mL; i.e., 2.2 mL daily. 
15.1.2. 
Vamorolone 4.0% Suspension Dispensing Guide 
Each subject enrolled in the study will be dispensed 125 ml bottle(s) of vamorolone 4.0% 
suspension at the Baseline Day 1 Visit, sufficient for dosing through the time of the 

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scheduled Week 6 Visit.  Additional supplies will be dispensed at the Week 6 Visit, 
sufficient for dosing through the time of the scheduled Week 12 Visit.  Subjects whose 
vamorolone dose is tapered during the Dose-tapering Period will be dispensed additional 
vamorolone 4.0% suspension at the Week 12 Visit, sufficient for dose tapering to 
0.0 mg/kg/day (see Section 6.3.5). 
The number of bottles to be dispensed at each dispensing visit for the following 6-week 
dosing period is calculated by multiplying the subject’s daily dose (in mL/day) (as 
calculated by Equation 1) by 49 days (42 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 49 Days 
= #Bottles to be Dispensed 
for 6 weeks dosing 
100 mL 
 
Example 3: Calculation of number of bottles to be dispensed for 6-week dosing for a subject 
taking a daily dose of 1.2 mL (from Example 1 above): 
Daily Dose (1.2 mL/day) x 49 Days 
= 0.59 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 6-week dosing for a subject 
taking a daily dose of 2.2 mL (from Example 2 above):  
Daily Dose (2.2 mL/day) x 49 Days 
= 1.1 Bottles 
100 mL 
The number of bottles dispensed is rounded to the nearest whole integer, or 2 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 the Week 6 and Week 12 
Visits, respectively, and at the end of the Dose-tapering Period, if applicable, and retained 
at the clinical study site for investigational drug accountability monitoring. 

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15.2. 
Protocol Amendment #1 Complete List of Changes 
The following changes have been incorporated into the protocol under this protocol 
amendment, as summarized in the 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) are not included.  
Study Synopsis, Investigational Drug Product 
Original Text:  
Vamorolone, 4.0% wt/wt suspension for oral dosing 
Revised Text: 
Vamorolone, 4.0% wt/vol suspension for oral dosing 
 
Study Synopsis, Study Drug Formulation, Dosage & Administration 
Original Text:  
Treatment Period and Dose-tapering Period 
Subjects will be administered 4.0% wt/wt oral suspension (Formulation ROS2).   
All subjects in both age groups: vamorolone 4.0% wt/wt oral suspension 
(investigational medicine) will be administered once daily over the 12-week Treatment 
Period (Weeks 1-12) and during the 4-week Dose-tapering Period, as applicable.  The 
site pharmacist will dispense study medication in 110 mL bottles sufficient for 6 weeks 
of dosing (4 weeks for Dose-tapering Period) plus overage to subjects at the Day 1 and 
Week 6 Visits (and Week 12 Visit to subjects participating in the Dose-tapering 
Period), according to the subject’s assignment to a dose group and subject body weight 
recorded at the dispensing visit (Day -1 weight for Day 1 dispensing).   
Revised Text: 
Treatment Period and Dose-tapering Period 
Subjects will be administered 4.0% wt/vol oral suspension (Formulation route of 
synthesis 2 [ROS2]).   
All subjects in both age groups: vamorolone 4.0% wt/vol oral suspension 
(investigational medicine) will be administered once daily over the 12-week Treatment 
Period (Weeks 1-12) and during the 4-week Dose-tapering Period, as applicable.  The 
site pharmacist will dispense study medication in 125 mL bottles sufficient for 6 weeks 
of dosing (4 weeks for Dose-tapering Period) plus overage to subjects at the Day 1 and 
Week 6 Visits (and Week 12 Visit to subjects participating in the Dose-tapering 

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Period), according to the subject’s assignment to a dose group and subject body weight 
recorded at the dispensing visit (Day -1 weight for Day 1 dispensing).   
 
Study Synopsis, Study Drug Formulation, Dosage & Administration 
Original Text:  
The daily dose of study medication should be taken in the morning with breakfast. 
There are no other food or drink restrictions before or after dosing. 
Revised Text: 
Participants must fast ≥6 hours prior to the Day1, Week 2, Week 6, and Week 12 study 
visits, when dosing will occur at the study site. The daily dose of study medication 
administered at home should be taken in the morning with breakfast. There are no other 
food or drink restrictions before or after dosing. 
 
Study Synopsis, Study Summary 
Original Text:  
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1.  For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit.  Study drug dosing will occur at home on all days except 
dates of the Day 1, Week 2, and Week 12 Visits, when dosing will occur at the study 
site. 
Revised Text: 
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1.  For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit.  Study drug dosing will occur at home on all days except 
dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when dosing will occur at 
the study site. 
 

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Study Synopsis, Safety Measures 
Original Text:  
Weight and Height (standing height collected for subjects in 2-<4 years age group; 
height calculated from ulnar length in subjects in 7-<18 years age group) 
Revised Text: 
Weight and Height (standing height collected for subjects in 2 to <4 years age group 
and all participants who can stand independently; height calculated from ulnar length 
in subjects in 7 to <18 years age group) 
 
3.2 Study Summary, Paragraph 7 
Original Text:  
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1.  For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit (see Section 5.3).  Study drug dosing will occur at home 
on all days except dates of the Day 1, Week 2, and Week 12 Visits, when dosing will 
occur at the study site. 
Revised Text: 
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1.  For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit (see Section 5.3).  Study drug dosing will occur at home 
on all days except dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when 
dosing will occur at the study site. 
 
3.3 Dose group assignment, Paragraph 4 
Original Text:  
Assignment to dose group will require the site investigator, or designee, to verify that 
the subject meets the inclusion/exclusion criteria of the study.  The following 
information will be sent to the TRiNDS Study Coordinator: 
x Participant’s Study Subject Identification Number 
x Participant’s Date of Birth 

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x Participant’s glucocorticoid status at entry (7 to <18 years only) 
Revised Text: 
Assignment to dose group will require the site investigator, or designee, to verify that 
the subject meets the inclusion/exclusion criteria of the study.  The following 
information will be sent to the TRiNDS Study Coordinator: 
x Participant’s Study Subject Identification Number 
x Participant’s Age at Enrollment 
x Participant’s glucocorticoid status at entry (7 to <18 years only) 
 
4.1 Subject Enrollment and Identification Log, Paragraph 2 
Original Text:  
A subject enrollment log will be maintained at each investigational site for all subjects 
who are screened for the study, including those not assigned to treatment.  Limited data 
will be collected for these subjects, including date of birth and reason for exclusion 
from the study.  Subject enrollment logs will be maintained for all subjects enrolled in 
the study.  This record will also include the dates of subject enrollment and 
completion/termination.   
Revised Text:  
A subject enrollment log will be maintained at each investigational site for all subjects 
who are screened for the study, including those not assigned to treatment.  Limited data 
will be collected for these subjects, including age at enrollment and reason for 
exclusion from the study.  Subject enrollment logs will be maintained for all subjects 
enrolled in the study.  This record will also include the dates of subject enrollment and 
completion/termination.   
 
5.1 Study Medication Administered, Paragraph 1 
Original Text:  
Planned vamorolone dose levels: 2.0 mg/kg and 6.0 mg/kg. Doses can be adjusted 
based on PK and safety data from the first 6 patients per age group to avoid over- or 
under exposure and to achieve a consistent vamorolone AUC across the entire pediatric 
age range 
Revised Text: 
Planned vamorolone dose levels: 2.0 mg/kg/day and 6.0 mg/kg/day. Doses can be 
adjusted based on PK and safety data from the first 6 patients per age group to avoid 
over- or under exposure and to achieve a consistent vamorolone AUC across the entire 
pediatric age range. 

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5.1 Study Medication Administered, Paragraph 5 
Original Text:  
Vamorolone 4.0% wt/wt oral suspension (investigational medicine) will be 
administered to all subjects once daily for 12 weeks, from Study Day 1 until the 
Week 12 Visit.  At the end of the 12-week Treatment Period, a subset of subjects may 
receive additional vamorolone treatment in a dose-tapering manner during a 4-week 
Dose-tapering Period prior to discharge from the study (see Section 6.3.5). 
Revised Text: 
Vamorolone 4.0% wt/vol oral suspension (investigational medicine) will be 
administered to all subjects once daily for 12 weeks, from Study Day 1 until the 
Week 12 Visit.  At the end of the 12-week Treatment Period, a subset of subjects may 
receive additional vamorolone treatment in a dose-tapering manner during a 4-week 
Dose-tapering Period prior to discharge from the study (see Section 6.3.5). 
 
5.2 Identity of Investigational Product 
Original Text:  
ReveraGen BioPharma, Inc. will supply the following investigational study 
medication: 
Active Substance: 
Vamorolone 
Strength: 
 
4.0% wt/wt 
Dosage Form:  
Oral suspension 
Formulation:  
ROS2 
Manufacturer:  
Purna Pharmaceuticals NV/SA 
Revised Text:  
ReveraGen BioPharma, Inc. will supply the following investigational study 
medication: 
Active Substance: 
Vamorolone 
Strength: 
 
4.0% wt/vol 
Dosage Form:  
Oral suspension 
Formulation:  
ROS2 
Manufacturer:  
Purna Pharmaceuticals NV/SA 
 

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5.3 Dosage Schedule and Administration of Study Medication 
Original Text:  
Subjects in the 2 to <4 years age group and subjects in the 7 to <18 years age group 
will be administered vamorolone 4.0% wt/wt oral suspension (Formulation ROS2).   
All subjects in both age groups will receive study medication, administered orally once 
daily for 12 weeks, from Study Day 1 to the Week 12 Visit.  At the end of the 12-week 
Treatment Period, subjects who will not continue directly with further vamorolone or 
SoC glucocorticoid treatment at the end of the study will be tapered off suspension 
study medication over a 4-week Dose-tapering Period, prior to discharge from the 
study (see Section 6.3.5). 
The site pharmacist or designated site study staff will dispense study medication to 
each  subject in 110 mL bottles sufficient for 6 weeks of dosing (4 weeks for Dose-
tapering Period) plus overage at the Day 1 Visit, just prior to dosing, and at the Week 6 
Visit (and Week 12 Visit to subjects participating in the Dose-tapering Period), 
according to the subject’s dose assignment and subject body weight (in kg) recorded at 
the dispensing visit (Day -1 weight for Day 1 dispensing) (see Appendix 15.1 for a 
dose calculation worksheet). 
Each subject’s dose (in mL) will be calculated and written on the labels of the bottles 
to be dispensed at a given visit by trained site staff based on the weight of the subject 
(in kg) recorded at the dispensing visit.  The dispensed study medication bottle(s) will 
be returned to the study site at each subsequent scheduled study visit.  Study 
medication suspension dispensed at the Day 1 Visit should be brought in with the 
subject to the Week 2 Visit, for Week 2 dosing in-clinic and compliance monitoring; 
this study medication will be returned to the subject at the end of the Week 2 Visit for 
continued dosing through the Week 6 Visit; new study medication will not be 
dispensed at the Week 2 Visit.  
All subjects will receive all doses under the supervision of parents or legal guardians or 
trained study staff.  Dosing is to occur at home throughout the 12-week Treatment 
Period, except at the Day 1, Week 2, and Week 12 Visits when dosing will occur at the 
study site.  Subjects should receive each dose of study medication in the morning 
together with breakfast and at approximately the same time of day.  
Vamorolone suspension will be administered orally using a volumetric syringe 
supplied by the site.  Following administration of the dose of study drug suspension, 
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 breakfast.  There are no other food or 
drink restrictions before or after dosing.   
At the Day 1, Week 2, and Week 12 study visits, subjects will arrive at the study clinic 
and will eat breakfast at the study site within 30 minutes prior to administration of the 
dose of study medication. 

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Any missed or incomplete doses of study medication should be recorded in the Subject 
Diary and reported immediately to the site Investigator. 
Revised Text:  
Subjects in the 2 to <4 years age group and subjects in the 7 to <18 years age group 
will be administered vamorolone 4.0% wt/vol oral suspension (Formulation ROS2).   
All subjects in both age groups will receive study medication, administered orally once 
daily for 12 weeks, from Study Day 1 to the Week 12 Visit.  At the end of the 12-week 
Treatment Period, subjects who will not continue directly with further vamorolone or 
SoC glucocorticoid treatment at the end of the study will be tapered off suspension 
study medication over a 4-week Dose-tapering Period, prior to discharge from the 
study (see Section 6.3.5). 
The site pharmacist or designated site study staff will dispense study medication to 
each  subject in 125 mL bottles sufficient for 6 weeks of dosing (4 weeks for Dose-
tapering Period) plus overage at the Day 1 Visit, just prior to dosing, and at the Week 6 
Visit (and Week 12 Visit to subjects participating in the Dose-tapering Period), 
according to the subject’s dose assignment and subject body weight (in kg) recorded at 
the dispensing visit (Day -1 weight for Day 1 dispensing) (see Appendix 15.1 for a 
dose calculation worksheet). 
Each subject’s dose (in mL) will be calculated and written on the labels of the bottles 
to be dispensed at a given visit by trained site staff based on the weight of the subject 
(in kg) recorded at the dispensing visit.  The dispensed study medication bottle(s) will 
be returned to the study site at each subsequent scheduled study visit.  Study 
medication suspension dispensed at the Day 1 Visit should be brought in with the 
subject to the Week 2 Visit, for Week 2 dosing in-clinic and compliance monitoring; 
this study medication will be returned to the subject at the end of the Week 2 Visit for 
continued dosing through the Week 6 Visit; new study medication will not be 
dispensed at the Week 2 Visit.  
All subjects will receive all doses under the supervision of parents or legal guardians or 
trained study staff.  Dosing is to occur at home throughout the 12-week Treatment 
Period, except at the Day 1, Week 2, Week 6, and Week 12 Visits when dosing will 
occur at the study site.  Subjects should receive each dose of study medication in the 
morning together with breakfast and at approximately the same time of day. On days 
where vamorolone is administered in clinic, subjects should arrive fasted for >6 hours 
and should eat breakfast with their dose of study drug.  
Vamorolone suspension will be administered orally using a volumetric syringe 
supplied by the site.  Following administration of the dose of study drug suspension, 
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 breakfast.  There are no other food or 
drink restrictions before or after dosing.   

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 146 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
At the Day 1, Week 2, Week 6, and Week 12 study visits, subjects will arrive at the 
study clinic and will eat breakfast at the study site after collection of fasting lab 
samples and within 30 minutes prior to administration of the dose of study medication. 
Any missed or incomplete doses of study medication should be recorded in the Subject 
Diary and reported immediately to the site Investigator. 
 
5.5 Treatment Compliance 
Original Text:  
Subject compliance with the dosing schedule will be assessed by site maintenance of 
accurate study drug dispensing and return records, and accurate recording of 
incomplete or missed doses by completion of a diary by the subject’s parent or 
guardian.  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(s) or guardian(s) with regard to proper dosing of study medication and 
completion of subject diaries, and will reinforce the importance of taking all study 
medication per protocol instructions.  Doses of study drug on the days of the Day 1, 
Week 2, and Week 12 Visits will be administered at the participating study site by a 
trained investigational staff member.  All incomplete or missed doses are to be 
documented in the source document and on the appropriate eCRF page.  The volume of 
unused study medication remaining in each bottle returned, as measured by the weight 
of returned bottles, will be documented in the source documents and on the appropriate 
eCRF page. 
Revised Text:  
Subject compliance with the dosing schedule will be assessed by site maintenance of 
accurate study drug dispensing and return records, and accurate recording of 
incomplete or missed doses by completion of a diary by the subject’s parent or 
guardian.  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(s) or guardian(s) with regard to proper dosing of study medication and 
completion of subject diaries and will reinforce the importance of taking all study 
medication per protocol instructions.  Doses of study drug on the days of the Day 1, 
Week 2, Week 6, and Week 12 Visits will be administered at the participating study 
site by a trained investigational staff member.  All incomplete or missed doses are to be 
documented in the source document and on the appropriate eCRF page.  The volume of 
unused study medication remaining in each bottle returned, as measured by the weight 
of returned bottles, will be documented in the source documents and on the appropriate 
eCRF page. 
 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 147 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
5.8.1 Packaging and Labeling of Study Medication, Paragraph 1 
Original Text:  
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.  The Study Sponsor through the designated central 
pharmacy will provide CTM in bulk quantities sufficient to satisfy the protocol 
requirement.  Vamorolone 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 120 mL (4 oz) amber bottles with a 110 
mL fill volume with child-resistant cap with a 24 mm bottle press in adapter.  Bottles 
are filled with 110 mL of suspension in order to guarantee a delivery of 100 mL.   
Revised Text:  
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.  The Study Sponsor through the designated central 
pharmacy will provide CTM in bulk quantities sufficient to satisfy the protocol 
requirement.  Vamorolone 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 125 mL (4 oz) amber bottles with a 100 
mL fill volume with child-resistant cap with a 28 mm bottle press in adapter.  
 
Table 7. 
Schedule of Study Activities 
Original Text: Table 7. 
Schedule of Study Activities 
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Informed consent 
X 
 
 
 
 
 
 
 
Enrollmentf 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
Assignmentg 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Medication history 
X 
X 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
X 
X 
 
X 
Cushingoid features 
X 
X 
 
 
X 
X 
 
X 
Heighth 
X 
 
 
 
 
X 
 
 
Weight 
X 
X 
 
X 
X 
X 
 
X 
Vital signsi 
X 
X 
Xj 
X 
X 
X 
 
X 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 148 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Blood for clinical 
labsk 
X 
 
Xl 
 
 
Xl 
 
X 
Blood for vitamin D 
X 
 
 
 
 
Xl 
 
 
Confirmation of 
varicella immunity 
X 
 
 
 
 
 
 
 
Urinalysism 
X 
 
X 
 
X 
X 
 
X 
Blood for serum PD 
biomarker paneln 
 
 
Xl 
 
 
Xl 
 
 
Fasting blood for 
insulin, glucose 
 
 
Xl 
 
 
Xl 
 
 
Blood for HbA1c 
X 
 
 
 
 
Xl 
 
 
Blood for morning 
cortisolo 
 
 
Xl 
 
 
Xl 
 
 
Blood for Plasma PK 
 
 
Xp 
Xp 
 
 
 
 
12-lead ECGq 
X 
 
 
 
 
X 
 
 
Eye examination 
X 
 
 
 
 
X 
 
 
Dispense study 
medication 
 
 
X 
 
X 
Xr 
 
 
Return study 
medication/ 
compliance 
monitoring 
 
 
 
Xs 
X 
X 
 
X 
Study medication 
dosingt 
 
 
X 
 
 
X 
 
 
Study medication 
dose tapering 
 
 
 
 
 
Xr 
 
X 
Telephone call to 
subject 
 
 
 
 
 
 
Xu 
 
Bayley-III Gross 
Motorv 
X 
X 
 
 
 
X 
 
 
PUL Testw 
X 
X 
 
 
 
X 
 
 
Pediatric Outcomes 
Data Collection 
Instrument (PODCI) 
X 
 
 
 
 
X 
 
 
PARS III 
X 
 
 
 
 
X 
 
 
Ease of Study 
Medication 
Administration 
Assessmentx 
 
 
 
 
X 
X 
 
 
Study Medication 
Acceptability 
Assessmenty 
 
 
 
 
X 
X 
 
 
Dispense subject 
diariesz 
 
 
X 
X 
X 
Xq 
 
 
Return subject diaries 
 
 
 
X 
X 
X 
 
X 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 149 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
AE/SAE recordingaa 
X 
 
 
 
 
 
 
Xbb 
Prior/Concomitant 
medications 
X 
 
 
 
 
 
 
X 
Discharge from study 
 
 
 
 
 
Xcc 
 
Xdd 
BL = Baseline; d = day(s); SCR = Screening.  
a. 
Only subjects who will not transition directly to further vamorolone or SoC glucocorticoid 
treatment at the end of the 12-week Treatment Period will begin a 4week open-label Dosetapering 
Period during which the dose of study medication will be progressively reduced and discontinued. 
b. All Day -1 assessments must be completed within 24 hours prior to administration of the first dose 
of study medication on Day 1.  
c. 
Time windows around the Week 2, Week 6, and Week 12 Visits are allowances from date of Day 
1 Visit; time window around Week 16 Visit is allowance from date of Week 12 Visit. 
d. Subjects who prematurely discontinue from the study prior to Week 12 should complete the 
Week 12 assessments at the time of early withdrawal and undergo Dose-tapering, where 
appropriate.   
e. 
Subjects will have one study site visit during the Dose-tapering Period, at one week after the dose 
of study medication has been discontinued (Week 16).  
f. 
Subjects are considered to be enrolled in the study at the time written informed consent is 
obtained. 
g. Assignment to a treatment group is done by the TRiNDS Study Coordinator at the Baseline Day -1 
Visit. 
h. Standing height will be measured for subjects in the 2- <4 years age group; ulnar length will be 
measured and used to calculate height for subjects in the 7 to <18 years age group. 
i. 
Sitting blood pressure, body temperature, respiratory rate, and heart rate. 
j. 
Vital signs recorded prior to administration of the first dose of study drug at the Day 1 Visit. 
k. Blood for hematology, chemistry, and lipids.  
l. 
Blood samples collected after subjects have fasted for ≥ 6 hours, and prior to daily dose of study 
drug.   
m. Urinalysis by dipstick and microscopic analysis. 
n. Blood collected for PD biomarkers includes exploratory safety outcomes (osteocalcin, CTX, P1NP) at 
Day 1 pre-dose and Week 12 predose.  Blood remaining from collected blood samples not needed for 
protocol-specified analyses may be stored for future exploratory biomarker studies for aspects of safety 
and efficacy.  All pre-dose samples should be collected after subject has fasted for ≥ 6 hours.   
o. Blood collected for morning cortisol should be collected before 10 AM local time. 
p. Blood samples for population PK analysis will be collected within 30 minutes pre-dose and at 1, 2, 
and 6 hours post-dose at the Day 1 and Week 2 Visits (2 to <4 years), and within 30 minutes pre-
dose, and at 1, 2, 4, 6 and 8 hours post-dose at the Day 1 and Week 2 Visits (7 to <18 years). 
q. 12-lead ECG recorded after subject has rested quietly in a supine position for at least 5 minutes. 
r. 
Only for subjects participating in the Dose-tapering Period. 
s. 
Study medication brought by subjects to the Week 2 Visit for dosing and compliance assessment 
will be redispensed to subjects at the end of the visit. 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 150 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
t. 
During the Treatment Period, the dose of study medication on the days of the Day 1, Week 2, 
Week 6, and Week 12 Visits will be administered with breakfast in the study clinic.  All other 
doses will be taken with breakfast at home.   
u. Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to ensure that the 
study drug tapering is proceeding according to protocol, to assess potential signs or symptoms 
indicative of adrenal suppression, and to address any questions the parent(s)/guardian(s) may have.  
v. Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale will be 
completed for subjects in the 2 to <4 years age group only. 
w. Performance of Upper Limb (PUL) test will be performed by subjects in the 7 to <18 years age 
group only. 
x. Ease of Study Medication Administration Assessment will be completed for subjects in the 2 to <4 
years age group only. 
y. Study Medication Acceptability Assessment will be completed by subjects in the 7 to <18 years 
age group only. 
z. 
Subject diaries used to record any changes in concomitant medications taken, any AEs 
experienced during the study, and any incomplete or missed doses of study medication. 
aa. All AEs and SAEs must be recorded in the source documents and eCRF from the date of the subject’s 
written informed consent until the final Week 16 Visit or the subject’s participation in the study is 
completed (SAEs through 30 days after final dose study drug).  Ongoing AEs will be followed to 
resolution, stabilization, or until such time the Investigator believes follow-up is not necessary. 
bb. For subjects who do not continue into an expanded access or compassionate use program, site staff will 
make a phone call to the home 31-35 days after the final dose of study medication in VBP15-006 
Dose-tapering Period to confirm the final SAE status of the subject. 
cc. Subjects who elect to continue vamorolone therapy by enrolling directly into an expanded access or 
compassionate use program or who will transition directly to SoC glucocorticoid therapy may be 
discharged from the study following completion of all final Week 12 assessments. 
dd. Subjects who participate in the Dose-tapering Period may be discharged from the study following 
completion of all final Dose-tapering Visit assessments (Week 16). 
 
Revised Text:  
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Informed consent 
X 
 
 
 
 
 
 
 
Enrollmentf 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
Assignmentg 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Medication history 
X 
X 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
X 
X 
 
X 
Cushingoid features 
X 
X 
 
 
X 
X 
 
X 
Heighth 
X 
 
 
 
 
X 
 
 
Weight 
X 
X 
 
X 
X 
X 
 
X 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 151 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Vital signsi 
X 
X 
Xj 
X 
X 
X 
 
X 
Blood for clinical 
labsk 
X 
 
Xl 
 
Xl 
Xl 
 
X 
Blood for vitamin D 
X 
 
 
 
 
Xl 
 
 
Confirmation of 
varicella immunity 
X 
 
 
 
 
 
 
 
Urinalysism 
X 
 
X 
 
X 
X 
 
X 
Blood for serum PD 
biomarker paneln 
 
 
Xl 
 
 
Xl 
 
 
Fasting blood for 
insulin, glucose 
 
 
Xl 
Xl 
Xl 
Xl 
 
 
Blood for HbA1c 
X 
 
 
 
 
Xl 
 
 
Blood for morning 
cortisolo 
 
 
Xl 
 
 
Xl 
 
 
Blood for Plasma PK 
 
 
Xp 
Xp 
 
 
 
 
12-lead ECGq 
X 
 
 
 
 
X 
 
 
Eye examination 
X 
 
 
 
 
X 
 
 
Dispense study 
medication 
 
 
X 
 
X 
Xr 
 
 
Return study 
medication/ 
compliance 
monitoring 
 
 
 
Xs 
X 
X 
 
X 
Study medication 
dosingt 
 
 
X 
 
 
X 
 
 
Study medication 
dose tapering 
 
 
 
 
 
Xr 
 
X 
Telephone call to 
subject 
 
 
 
 
 
 
Xu 
 
Bayley-III Gross 
Motorv 
X 
X 
 
 
 
X 
 
 
PUL Testw 
X 
X 
 
 
 
X 
 
 
Pediatric Outcomes 
Data Collection 
Instrument (PODCI) 
X 
 
 
 
 
X 
 
 
PARS III 
X 
 
 
 
 
X 
 
 
Ease of Study 
Medication 
Administration 
Assessmentx 
 
 
 
 
X 
X 
 
 
Study Medication 
Acceptability 
Assessmenty 
 
 
 
 
X 
X 
 
 
Dispense subject 
diariesz 
 
 
X 
X 
X 
Xq 
 
 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 152 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
 
Pretreatment Period 
Treatment Period 
Dose-tapering 
Perioda 
SCR 
BL 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b  
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Return subject diaries 
 
 
 
X 
X 
X 
 
X 
AE/SAE recordingaa 
X 
 
 
 
 
 
 
Xbb 
Prior/Concomitant 
medications 
X 
 
 
 
 
 
 
X 
Discharge from study 
 
 
 
 
 
Xcc 
 
Xdd 
BL = Baseline; d = day(s); SCR = Screening.  
a. 
Only subjects who will not transition directly to further vamorolone or SoC glucocorticoid 
treatment at the end of the 12-week Treatment Period will begin a 4-week open-label 
Dose-tapering Period during which the dose of study medication will be progressively reduced and 
discontinued. 
b. All Day -1 assessments must be completed within 24 hours prior to administration of the first dose 
of study medication on Day 1.  
c. 
Time windows around the Week 2, Week 6, and Week 12 Visits are allowances from date of Day 
1 Visit; time window around Week 16 Visit is allowance from date of Week 12 Visit. 
d. Subjects who prematurely discontinue from the study prior to Week 12 should complete the 
Week 12 assessments at the time of early withdrawal and undergo Dose-tapering, where 
appropriate.   
e. 
Subjects will have one study site visit during the Dose-tapering Period, at one week after the dose 
of study medication has been discontinued (Week 16).  
f. 
Subjects are considered to be enrolled in the study at the time written informed consent is 
obtained. 
g. Assignment to a treatment group is done by the TRiNDS Study Coordinator at the Baseline Day -1 
Visit. 
h. Standing height will be measured for subjects in the 2 to <4 years age group and participants ages 
7 to <18 years who can stand independently; ulnar length will be measured and used to calculate 
height for subjects in the 7 to <18 years age group. 
i. 
Sitting blood pressure, body temperature, respiratory rate, and heart rate. 
j. 
Vital signs recorded prior to administration of the first dose of study drug at the Day 1 Visit. 
k. Blood for hematology, chemistry, and lipids. All samples should be collected after subject has 
fasted for >6 hours.  
l. 
Blood samples collected after subjects have fasted for ≥ 6 hours, and prior to daily dose of study 
drug.   
m. Urinalysis by dipstick and microscopic analysis. 
n. Blood collected for PD biomarkers includes exploratory safety outcomes of bone turnover (osteocalcin, 
CTX, P1NP) at Day 1 pre-dose and Week 12 pre-dose.  Blood remaining from collected blood samples 
not needed for protocol-specified analyses may be stored for future exploratory biomarker studies for 
aspects of safety and efficacy.  All pre-dose samples should be collected after subject has fasted for ≥ 6 
hours.   
o. Blood collected for morning cortisol should be collected before 10 AM local time. 
p. Blood samples for population PK analysis will be collected within 30 minutes pre-dose and at 1, 2, 
and 6 hours post-dose at the Day 1 and Week 2 Visits (ages 2 to <4 years), and within 30 minutes 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 153 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
pre-dose, and at 1, 2, 4, 6 and 8 hours post-dose at the Day 1 and Week 2 Visits (ages 7 to <18 
years). 
q. 12-lead ECG recorded after subject has rested quietly in a supine position for at least 5 minutes. 
r. 
Only for subjects participating in the Dose-tapering Period. 
s. 
Study medication brought by subjects to the Week 2 Visit for dosing and compliance assessment 
will be redispensed to subjects at the end of the visit. 
t. 
During the Treatment Period, the dose of study medication on the days of the Day 1, Week 2, 
Week 6, and Week 12 Visits will be administered with breakfast in the study clinic.  All other 
doses will be taken with breakfast at home.   
u. Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to ensure that the 
study drug tapering is proceeding according to protocol, to assess potential signs or symptoms 
indicative of adrenal suppression, and to address any questions the parent(s)/guardian(s) may have.  
v. Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale will be 
completed for subjects in the 2 to <4 years age group only. 
w. Performance of Upper Limb (PUL) test will be performed by subjects in the 7 to <18 years age 
group only. 
x. Ease of Study Medication Administration Assessment will be completed for subjects in the 2 to <4 
years age group only. 
y. Study Medication Acceptability Assessment will be completed by subjects in the 7 to <18 years 
age group only. 
z. 
Subject diaries used to record any changes in concomitant medications taken, any AEs 
experienced during the study, and any incomplete or missed doses of study medication. 
aa. All AEs and SAEs must be recorded in the source documents and eCRF from the date of the subject’s 
written informed consent until the final Week 16 Visit or the subject’s participation in the study is 
completed (SAEs through 30 days after final dose study drug).  Ongoing AEs will be followed to 
resolution, stabilization, or until such time the Investigator believes follow-up is not necessary. 
bb. For subjects who do not continue into an expanded access or compassionate use program, site staff will 
make a phone call to the home 31-35 days after the final dose of study medication in VBP15-006 
Dose-tapering Period to confirm the final SAE status of the subject. 
cc. Subjects who elect to continue vamorolone therapy by enrolling directly into an expanded access or 
compassionate use program or who will transition directly to SoC glucocorticoid therapy may be 
discharged from the study following completion of all final Week 12 assessments. 
dd. Subjects who participate in the Dose-tapering Period may be discharged from the study following 
completion of all final Dose-tapering Visit assessments (Week 16). 
 
6.3.1 Screening Period (Day -33 to -2), Paragraph 2 
Original Text:  
Following the signing of the written ICF, subjects will be considered to be enrolled in 
the study, and will be assigned a unique site-specific 6-digit subject ID number that 
will be comprised of protocol, site, and subject numbers in sequential order of 
screening into the study.  All data will be identified using the unique subject ID 
number.  The site Investigator will keep a record relating the names of the subjects to 
their subject ID 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.  The Coordinating Center will not collect 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
Page 154 of 232 
Santhera Pharmaceuticals Ltd – CONFIDENTIAL 
names or other identifiers except dates (diagnosis, study visits), date of birth, and the 
subject ID number. 
Revised Text:  
Following the signing of the written ICF, subjects will be considered to be enrolled in 
the study and will be assigned a unique site-specific 6-digit subject ID number that will 
be comprised of protocol, site, and subject numbers in sequential order of screening 
into the study.  All data will be identified using the unique subject ID number.  The site 
Investigator will keep a record relating the names of the subjects to their subject ID 
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.  The Coordinating Center will not collect names or other 
identifiers except dates (diagnosis, study visits), age at enrollment, and the subject ID 
number. 
 
6.3.4 Treatment Period (Weeks 1-12), Paragraphs 1-3 
Original Text:  
Subjects will return to the study site for safety, PK, clinical efficacy, PD, behavior and 
neuropsychology, and physical functioning beginning at Week 2 and continuing 
through the Week 12 Visit, according to the schedule of assessments in Table 7.   
Subjects will continue to receive daily oral administration of vamorolone suspension 
according to their assigned treatment throughout the 12-week Treatment Period.  The 
daily dose of study medication should be taken with breakfast.  
Dosing is to occur at home throughout the 12-week Treatment Period, except at the 
Weeks 2 and 12 study visits, when dosing will occur at the study site.  Subjects must 
have fasted ≥ 6 hours prior to arrival at the study site for the Weeks 2 and 12 study 
visits.  Breakfast will be served at the study site after the blood collections for clinical 
laboratory tests and Vitamin D (Week 12 only); pre-dose blood draw for plasma PK 
analysis (Week 2 only); and blood draws for PD biomarkers, including insulin, 
glucose, HbA1c, morning cortisol, osteocalcin, CTX, P1NP (Week 12 only); and 
within 30 minutes prior to administration of the dose of study medication.  Blood 
samples for plasma PK analysis will also be collected pre-dose and at several time 
points post-dose at the Week 2 Visit (see Section 7.2.7).  Ease of Administration of 
Study Medication Administration (ages 2 to <4 years) and Study medication 
Acceptability (7 to <18 years) will be assessed at the Weeks 6 and 12 Visits.  Apart 
from blood and urine sample collections, all other scheduled assessments should be 
performed after administration of the study medication in clinic.    
Revised Text:  
Subjects will return to the study site for safety, PK, clinical efficacy, PD, behavior and 
neuropsychology, and physical functioning assessments beginning at Week 2 and 

Vamorolone 
11 April 2023 
Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
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continuing through the Week 12 Visit, according to the schedule of assessments in 
Table 7.  
Subjects will continue to receive daily oral administration of vamorolone suspension 
according to their assigned treatment throughout the 12 week Treatment Period.  The 
daily dose of study medication should be taken with breakfast.  
Dosing is to occur at home throughout the 12-week Treatment Period, except at the 
Week 2, 6, and 12 study visits, when dosing will occur at the study site.  Subjects must 
have fasted ≥ 6 hours prior to arrival at the study site for the Weeks 2, 6, and 12 study 
visits.  Breakfast will be served at the study site after the blood collections for clinical 
laboratory tests (all visits) and Vitamin D (Week 12 only); pre-dose blood draw for 
plasma PK analysis (Week 2 only); and blood draws for PD biomarkers, including 
insulin, glucose, HbA1c, morning cortisol, osteocalcin, CTX, P1NP (Week 12 only); 
and within 30 minutes prior to administration of the dose of study medication.  Blood 
samples for plasma PK analysis will also be collected pre-dose and at several time 
points post-dose at the Week 2 Visit (see Section 7.2.7).  Ease of Administration of 
Study Medication Administration (ages 2 to <4 years) and Study Medication 
Acceptability (7 to <18 years) will be assessed at the Weeks 6 and 12 Visits.  Apart 
from blood and urine sample collections, all other scheduled assessments should be 
performed after administration of the study medication in clinic.    
 
6.4 Subject Discontinuation, Paragraph 1 
Original Text:  
Any subject who chooses to withdraw from the study after Day 1 and prior to the 
Week 12 Visit should return to the study site for Week 12 assessments at the time of 
early withdrawal, whenever possible (see Section 6.3.4), assuming the subject has not 
withdrawn consent, and will participate in the 4-week Dose-tapering Period.  Site 
personnel will document all assessments, including any AEs, in the source documents 
and eCRF.   
Revised Text:  
Any subject who chooses to withdraw from the study after Day 1 and prior to the 
Week 12 Visit should return to the study site for Week 12 assessments at the time of 
early withdrawal, whenever possible (see Section 6.3.4), assuming the subject has not 
withdrawn consent, and will participate in the 4-week Dose-tapering Period.  Site 
personnel will document and evaluate all assessments, including any AEs and lab 
results, in the source documents and eCRF.   
 

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6.4 Subject Discontinuation, Paragraph 9 
Original Text:  
Subjects will have non-fasting blood and urine samples collected for clinical laboratory 
tests at the final Early Termination/Week 16 Visit.  Subjects will also have a physical 
examination with weight, assessment of cushingoid features and vital signs recorded.  
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.   
Revised Text:  
Subjects will have non-fasting blood and urine samples collected for clinical laboratory 
tests at the final Early Termination/Week 16 Visit.  Subjects will also have a physical 
examination with weight, assessment of cushingoid features and vital signs recorded.  
Study medication will be returned for compliance monitoring.  Adverse events, 
including SAEs, lab results, and concomitant medications will be assessed and 
documented.  Subject diaries will be returned and reviewed with site staff.   
 
7.1 Demographic Assessments 
Original Text:  
Demographic information (birth date, race, and ethnicity) will be collected during the 
Pretreatment Screening Period and will be recorded on the appropriate eCRF page. 
Revised Text:  
Demographic information (age at enrollment, race, and ethnicity) will be collected 
during the Pretreatment Screening Period and will be recorded on the appropriate 
eCRF page. 
 
7.2.2 Physical Examination, Cushingoid Features, Weight, and Height,  
Paragraph 3 
Original Text:  
Height (in cm) will be recorded at Screening and Week 12.  Standing height will be 
recorded for subjects in the 2 to <4 years age group.  Ulnar length of the non-dominant 
arm, measured from the olecranon (point of elbow) to the styloid process (prominent 
bone of the wrist), will be used to calculate height for subjects in the 7 to <18 years age 
group (see Manual of Operations for a detailed description of methodology). 
Revised Text:  
Height (in cm) will be recorded at Screening and Week 12.  Standing height will be 
recorded for subjects in the 2 to <4 years age group and all participants in the 7 to <18 
years age group who can stand independently.  Ulnar length of the non-dominant arm, 

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measured from the olecranon (point of elbow) to the styloid process (prominent bone 
of the wrist), will be used to calculate height for subjects in the 7 to <18 years age 
group (see Manual of Operations for a detailed description of methodology). 
 
7.2.4 Clinical Laboratory Tests, Paragraph 1 
Original Text:  
Each subject will have blood drawn and urine collected for the hematology, chemistry, 
lipids, and urinalysis clinical laboratory tests listed in Table 8 and Table 9, below, 
during the Screening Period, at the Day 1, Week 6, Week 12, and Week 16 Visits.  
Blood for vitamin D is collected at the Screening and Week 12 Visits only.  Fasted 
blood samples for clinical laboratory tests will be collected pre-dose at the Day 1 and 
Week 12 Visits.  Non-fasted blood samples for clinical laboratory tests will be 
collected at the Screening, and Weeks 6 and 16 Visis. Urine samples may be collected 
non-fasting at all scheduled visits.  Details of blood and urine collections can be found 
in the Laboratory Manual. 
Revised Text:  
Each subject will have blood drawn and urine collected for the hematology, chemistry, 
lipids, and urinalysis clinical laboratory tests listed in Table 9 and Table 10 below, 
during the Screening Period, at the Day 1, Week 6, Week 12, and Week 16 Visits.  
Blood for vitamin D is collected at the Screening and Week 12 Visits only.  Fasted 
blood samples for clinical laboratory tests will be collected pre-dose at the Day 1, 
Week 2, Week 6, Week 12, and Week 16 Visits.  Urine samples may be collected non-
fasting at all scheduled visits.  Details of blood and urine collections can be found in 
the Laboratory Manual. 
 
7.2.4 Clinical Laboratory Tests, Table 9, Chemistry 
Original Text: 
Chemistry 
Sodium 
Total Bilirubina 
Potassium 
Uric Acid 
Chloride 
Glucose 
Calcium 
Glutamate dehydrogenase (GLDH) 
Inorganic Phosphorus 
Alkaline phosphatase (ALP) 
Blood Urea Nitrogen (BUN) 
Gamma Glutamyl Transferase (GGT) 
Creatinine 
Aspartate aminotransferase (AST) 
Total Protein 
Alanine aminotransferase (ALT) 
Albumin 
Creatine kinase (CK) 

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Bicarbonate 
Lipase 
Lactate Dehydrogenase (LDH) 
Amylase 
Cystatin C 
Vitamin Db 
 
Revised Text: Table 4. 
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) 
Vitamin Db 
Cystatin C 
 
 
7.2.7 Pharmacokinetic Assessment, Paragraph 4 
Original Text:  
If PK and PD or clinical laboratory blood samples are to be collected at the same time 
point, the PK blood sample should be collected prior to the PD blood sample(s), which 
in turn should be collected prior to the clinical laboratory blood samples. 
Revised Text:  
If PK and PD or clinical laboratory blood samples are to be collected at the same time 
point, the PK blood sample should be collected in the order specified in the laboratory 
collection flow chart. 
 
7.2.8 Total Blood Volume Required 
Original Text:  
The number and volume of blood samples and total volume of blood to be collected 
from each subject throughout the duration of the up-to-21-week study are summarized 
in Table 11.  A total of 49 mL of blood will be collected from each 2 to <4 year 

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subject, and 57 mL of blood will be collected from each 7 to <18 year subject over the 
course of the up to-21-week study. 
Revised Text:  
The number and volume of blood samples and total volume of blood to be collected 
from each subject throughout the duration of the up-to-21-week study are summarized 
in Table 12 A total of 48.3 mL of blood will be collected from each 2 to <4-year-old 
subject, and 52.3 mL of blood will be collected from each 7 to <18-year-old subject 
over the course of the up to-21-week study. 
 
7.2.8 Total Blood Volume Required, Table 12 
Original Text: Table 12 
 
Blood Volume (mL) 
Test 
SCR 
Day 1 
Week 2 
Week 6 
Week 12 Week 16 
Total 
Volume 
Clinical Safety Labsa 
3 
3b 
 
3 
3b 
3 
15 
Varicella Zoster IgG 
2 
 
 
 
 
 
2 
Vitamin D 
2 
 
 
 
2b 
 
4 
PD Biomarker Panelc 
 
5b 
 
 
5b 
 
10 
HbA1c 
1 
 
 
 
1b 
 
2 
PKd 
Ages 2 to <4 years 
Ages 7 to <18 years 
 
 
8 
12 
 
8 
12 
 
 
 
 
16 
24 
Total Volume by Visit (mL) 
Ages 2 to <4 years 
Ages 7 to <18 years 
8 
 
16 
20 
 
8 
12 
3 
11 
3 
 
49 
57 
Total Volume: 49 mL (2 to <4 year); 57 mL (7 to <18 year) 
SCR = Screening 
a Hematology, Chemistry, Lipids; volume includes blood for exploratory PD biomarkers. 
b Subjects must have fasted ≥ 6 hours prior to blood draws. 
c Fasting glucose, insulin, morning cortisol, CTX, P1NP, osteocalcin; pre-dose on Day 1 and Week 12.   
d Blood drawn for population PK within 30 minutes pre-dose and at 1, 2, and 6 hours post-dose at the Day 1 
and Week 2 Visits (2 to <4 year), or 30 minutes pre-dose and at 1, 2, 4, 6 and 8 hours post-dose at the Day 
1 and Week 2 Visits (7 to <18 year).  Subjects must be fasting at the time of collection of the Day 1 and 
Week 2 pre-dose samples. 
 
Revised Text: Table 7 

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Blood Volume (mL) 
Test 
SCR 
Day 1 
Week 2 
Week 6 
Week 12 Week 16 Total 
Volume 
Clinical Safety Labsa 
3.5b 
3.5b 
 
3.5b 
3.5b 
3.5b 
17.5 
Varicella Zoster IgG 
2 
 
 
 
 
 
2 
Vitamin D 
1.2 
 
 
 
1.2b 
 
2.4 
PD Biomarker Panelc 
 
8.2b 
 
 
8.2b 
 
16.4 
HbA1c 
1 
 
 
 
1b 
 
2 
PKd 
Ages 2 to <4 years 
Ages 7 to <18 years 
 
 
4 
6 
 
4 
6 
 
 
 
 
8 
12 
Total Volume by Visit (mL) 
Ages 2 to <4 years 
Ages 7 to <18 years 
7.7 
 
15.7 
17.7 
 
4 
6 
3.5 
13.9 
3.5 
 
48.3 
52.3 
Total Volume: 48.3 mL (ages 2 to <4 year); 52.3 mL (ages 7 to <18 year) 
SCR = Screening 
a Hematology, Chemistry, Lipids 
b Subjects must have fasted ≥ 6 hours prior to blood draws. 
c Fasting glucose, insulin, morning cortisol, CTX, P1NP, osteocalcin; pre-dose on Day 1 and Week 12.   
d Blood drawn for population PK within 30 minutes pre-dose and at 1, 2, and 6 hours post-dose at the Day 1 
and Week 2 Visits (ages 2 to <4 years), or 30 minutes pre-dose and at 1, 2, 4, 6 and 8 hours post-dose at the 
Day 1 and Week 2 Visits (ages 7 to <18 years).  Subjects must be fasting at the time of collection of the 
Day 1 and Week 2 pre-dose samples. 
 
7.6 Adverse Events and Serious Adverse Events 
Original Text:  
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.   
Revised Text:  
The condition of the subjects, inclusive of lab values, will be monitored throughout the 
duration of the study by the clinical site study team and by recording of AEs in subject 
diaries.   
7.6.3 Clinical Laboratory Test Abnormalities, Paragraph 1 
Original Text:  
Clinical laboratory test results will be recorded on the designated eCRF page.  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 

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in detail as indicated in the eCRF.  A description of the intensity scale can be found 
above. 
Revised Text:  
Clinical laboratory test results will be recorded on the designated eCRF page.  The 
intensity of abnormal clinical laboratory test results that are AEs will also be graded 
using current FDA and the Council for International Organizations of Medical Sciences 
(CIOMS) drug-induced liver injury (DILI) guidance and 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. 
 
10.3.2 Modified Intent-to-Treat (mITT) Population 
Original Text:  
All subjects who receive at least one dose of study medication and have at least one 
post-baseline assessment will be included in the mITT Population.  The mITT 
Population is the primary analysis population for clinical efficacy.  Subjects who 
receive at least one dose of study medication but never have post-baseline assessments 
will be excluded.  Results will be presented “as .” 
Revised Text:  
All subjects who receive at least one dose of study medication and have at least one 
post-baseline assessment will be included in the mITT Population.  The mITT 
Population is the primary analysis population for clinical efficacy.  Subjects who 
receive at least one dose of study medication but never have post-baseline assessments 
will be excluded.  Results will be presented “as randomized.” 
 
15.1 Vamorolone Dose Calculation Worksheet and Bulk Dispensing Guide, 
Paragraph 3 and First Example 
Original Text:  
Calculated dose volume will be rounded to the nearest 0.01 mL (1 mL syringe), 0.1 
mL (3 mL syringe), 0.2 mL (5 mL syringe), or 0.2 mL (10 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 5: Dose volume calculation for a subject receiving 2.0 mg/kg/day with a body 
weight of 23 kg:  
Subject Weight (23 kg) x Dose Level (2.0 mg/kg) 
= 1.15 mL 
40 mg/mL 
The subject will receive a daily dose volume of 1.15 mL per dose throughout the period 
until the next scheduled study medication dispensing visit.   Dose will be administered 
using a 3 mL volumetric syringe rounded to the nearest 0.2 mL, or 1.2 mL daily. 

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Revised Text: 
Calculated dose volume will be rounded to the nearest 0.01 mL (1 mL syringe), 0.2 
mL (5 mL syringe), or 0.2 mL (10 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 2.0 mg/kg/day with a body 
weight of 23 kg:  
Subject Weight (23 kg) x Dose Level (2.0 mg/kg) 
= 1.15 mL 
40 mg/mL 
The subject will receive a daily dose volume of 1.15 mL per dose throughout the period 
until the next scheduled study medication dispensing visit.  Dose will be administered using 
a 5 mL volumetric syringe rounded to the nearest 0.2 mL; i.e., 1.2 mL daily. 
 
15.1.2 Vamorolone 4.0% Suspension Dispensing Guide, Paragraph 1 
Original Text:  
Each subject enrolled in the study will be dispensed 100 ml bottle(s) of vamorolone 
4.0% suspension at the Baseline Day 1 Visit, sufficient for dosing through the time of 
the scheduled Week 6 Visit.  Additional supplies will be dispensed at the Week 6 Visit, 
sufficient for dosing through the time of the scheduled Week 12 Visit.  Subjects whose 
vamorolone dose is tapered during the Dose-tapering Period will be dispensed 
additional vamorolone 4.0% suspension at the Week 12 Visit, sufficient for dose 
tapering to 0.0 mg/kg/day (see Section 6.3.5). 
Revised Text: 
Each subject enrolled in the study will be dispensed 125 ml bottle(s) of vamorolone 
4.0% suspension at the Baseline Day 1 Visit, sufficient for dosing through the time of 
the scheduled Week 6 Visit.  Additional supplies will be dispensed at the Week 6 Visit, 
sufficient for dosing through the time of the scheduled Week 12 Visit.  Subjects whose 
vamorolone dose is tapered during the Dose-tapering Period will be dispensed 
additional vamorolone 4.0% suspension at the Week 12 Visit, sufficient for dose 
tapering to 0.0 mg/kg/day (see Section 6.3.5). 
 
 
 

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15.3. 
Protocol Amendment #2 Complete List of Changes 
A Protocol version tracking changes between Edition A1 version 1.1 and A2 version 1.0 
will be provided. 
The following changes have been incorporated into the protocol under this protocol 
amendment, as summarized in the Protocol Amendment Tracking, Reasons for Protocol 
Amendment #2. 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) are not included.  
 
Protocol cover page 
Original Text:  
Sponsor: 
 
ReveraGen BioPharma, Inc.  
 
 
 
155 Gibbs St. 
 
 
 
Suite 433 
 
 
 
Rockville, MD 20850 
Study Chair:  
 
 
 
Phone:  
 
 
 
Email:
  
 
Medical Monitor: 
 
 
 
 
Phone:  
 
 
 
Email:
 
Revised Text: 
Sponsor:   
 
Santhera Pharmaceuticals (Switzerland) Ltd 
 
 
 
Hohenrainstrasse 24 
 
 
 
4133 Pratteln 
 
 
 
SwitzerlandSanthera Pharmaceuticals Ltd 
 
 
Principal Investigator: Jean Mah, M.D. 
PI
PI
PI
PPD

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Email:
  
 
Medical Monitor: 
 
 
Email: 
 
 
 
SIGNATURES OF AGREEMENT FOR VBP15-006 
Original Text:  
Reviewed and Approved by: 
 
 
_________________________________ 
_____________________________ 
 
 
 
 
Date 
 
ReveraGen BioPharma, Inc. 
 
_________________________________ 
_____________________________ 
 
 
 
 
Date 
Study Chair 
Alberta Children’s Hospital Research Institute 
University of Calgary 
 
_________________________________ 
_____________________________ 
 
 
Date 
Medical Monitor 
 
ReveraGen BioPharma, Inc. 
 
Revised Text:  
Reviewed and Approved by: 
 
_________________________________ 
_____________________________ 
 
 
 
 
Date 
 
Santhera Pharmaceuticals Ltd 
 
 
 
PI
PI
PI
PI
PI
PI
PPD
PPD
PPD
PPD

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Investigator Protocol Agreement 
Original Text: 
PROTOCOL NUMBER: 
VBP15-006  
SPONSOR: 
ReveraGen BioPharma, Inc. 
DOCUMENT DATE: 14 April 2022 
________________________________________________________________________ 
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 set out in the 
Declaration of Helsinki listed in 21 CFR part 312, and ICH principles of Good 
Clinical Practice (GCP) and in accordance with all applicable laws, guidances and 
directives of the jurisdiction where the study is being conducted.  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, 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 COPY TO REVERAGEN BIOPHARMA, INC., OR 
DESIGNEE 
 
 

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Revised Text: 
PROTOCOL NUMBER: 
VBP15-006  
SPONSOR: 
Santhera Pharmaceuticals Ltd 
DOCUMENT DATE: 09 February 2023 
_____________________________________________________________________ 
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 Santhera Pharmaceuticals (Switzerland) 
Ltd.  
I agree to conduct the study according to this protocol and the obligations and 
requirements of clinical Investigators and all other requirements set out in the 
Declaration of Helsinki listed in 21 CFR part 312, and ICH principles of Good 
Clinical Practice (GCP) and in accordance with all applicable laws, guidances and 
directives of the jurisdiction where the study is being conducted.  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 Santhera Pharmaceuticals 
(Switzerland) Ltd 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 Santhera Pharmaceuticals (Switzerland) Ltd. 
For protocol amendments, I agree not to implement the amendment without 
agreement from Santhera Pharmaceuticals (Switzerland) Ltd 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 (WET-INK OR VALIDATED E-SIGNATURE) SIGNED 
AGREEMENT AT YOUR SITE AND SEND A SCANNED COPY OF THE SIGNED 

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ORIGINAL TO SANTHERA PHARMACEUTICALS (SWITZERLAND) LTD, OR 
DESIGNEE 
 
 
Study Synopsis, Name of the Sponsor 
Original Text:  
ReveraGen Bio Pharma, Inc 
 
Revised Text: 
Santhera Pharmaceuticals (Switzerland) Ltd 
 
 
Study Synopsis, Investigational Drug Product 
Original Text:  
Vamorolone, 4.0% wt/vol suspension for oral dosing 
Revised Text: 
Vamorolone, 4.0% weight per volume (wt/vol) suspension for oral dosing 
 
Study Synopsis, Drug substance 
Original Text:  
delta-1,4,9(11)-pregnatriene-17-alpha,21-dihydroxy-16-alpha-methyl-3,20-dione 
Revised Text: 
17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione 
 
Study Synopsis, Study Design 
Original Text:  
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day 
Pretreatment Baseline Period; a 3-month open-label Treatment Period (Weeks 1-12); 
and a 4-week open-label Dose-tapering Period (Week 13-16) for subjects who will not 
transition directly to further vamorolone or standard of care (SoC) glucocorticoid 
treatment at the end of the study. 

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Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent, is obtained.   
x 
Within the 2 to <4 years age group, the initial 10 eligible subjects will be 
assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  
The subsequent 10 eligible subjects will be assigned to the 6.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit. 
x 
Within the 7 to <18 years age group, both corticosteroid-treated and 
untreated, the initial 12 eligible subjects will be assigned to the 2.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit.  The subsequent 12 eligible 
subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline 
Day -1 Visit. 
Revised Text: 
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day 
Pretreatment Baseline Period; a 3-month open-label Treatment Period (Weeks 1-12); 
and a 4-week Dose-tapering Period for subjects who will not transition directly to 
further vamorolone or standard of care (SoC) glucocorticoid treatment at the end of the 
study. 
Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent and assent, as required, is obtained.   
x 
Within the 2 to <4 years age group, the initial 10 eligible subjects will be 
assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  
The subsequent 10 eligible subjects will be assigned to the 6.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit. 
x 
Within the 7 to <18 years age group (including an additional 12 to <18 years 
age group), both corticosteroid-treated and untreated, the initial 12 eligible 
subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline 
Day -1 Visit.  The subsequent 22 eligible subjects (including 10 subjects from 
the additional 12 to <18 years age group) will be assigned to the 6.0 mg/kg/day 
treatment group at the Baseline Day -1 Visit. 
 
Study Synopsis, Planned Sample Size 
Original Text:  
A total of approximately 24 subjects will be enrolled to treatment within the 7 to <18 
years age group, with 2.0 mg/kg/day groups enrolled first, as follows: 
x 
Vamorolone 2.0 mg/kg/day, steroid untreated at entry (n=6) 
x 
Vamorolone 2.0 mg/kg/day, steroid treated at entry (n=6) 
x 
Vamorolone 6.0 mg/kg/day, steroid untreated at entry (n=6) 

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x 
Vamorolone 6.0 mg/kg/day, steroid treated at entry (n=6)  
Revised Text: 
A total of approximately 34 subjects will be enrolled to treatment within the 7 to <18 
years age group, with 2.0 mg/kg/day groups enrolled first, as follows: 
x 
Vamorolone 2.0 mg/kg/day, steroid untreated at entry (n=6) 
x 
Vamorolone 2.0 mg/kg/day, steroid treated at entry (n=6) 
x 
Vamorolone 6.0 mg/kg/day, steroid untreated at entry (n=6) 
x 
Vamorolone 6.0 mg/kg/day, steroid treated at entry (n=6)  
x 
Vamorolone 6.0 mg/kg/day, 12 to <18 years and steroid treated at entry (n=10, 
additional group) 
 
Study Synopsis, Individual Subject, Study Duration 
Original Text:  
Up to approximately 21 weeks: 
x 
Screening Period: up to 5 weeks 
x 
Baseline Period: 1 day 
x 
Treatment Period: 12 weeks (Weeks 1-12) 
x 
Dose-tapering Period: 4 weeks (only for subjects who will not transition 
directly to further vamorolone or SoC glucocorticoid treatment at the end of the 
study) (Weeks 13-16) 
Revised Text: 
Up to approximately 21 weeks: 
x 
Screening Period: up to 5 weeks 
x 
Baseline Period: 1 day 
x 
Treatment Period: 12 weeks (Weeks 1-12) 
x 
Dose-tapering Period: 4 up to 8 weeks, only for subjects who will not transition 
directly to further vamorolone or SoC glucocorticoid treatment at the end of the 
study. 
 
 
Study Synopsis, Study Drug Formulation, Dosage & Administration 
Original Text:  

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Treatment Period and Dose-tapering Period 
Subjects will be administered 4.0% wt/vol oral suspension (Formulation route of 
synthesis 2 [ROS2]).   and individual patients receiving 2 mg/kg can increase their dose 
to the high dose level if deemed appropriate by the investigatorAll subjects in both age 
groups: vamorolone 4.0% wt/vol oral suspension (investigational medicine) will be 
administered once daily over the 12-week Treatment Period (Weeks 1-12) and during 
the 4-week Dose-tapering Period, as applicable.  The site pharmacist will dispense 
study medication in 125 mL bottles sufficient for 6 weeks of dosing (4 weeks for Dose-
tapering Period) plus overage to subjects at the Day 1 and Week 6 Visits (and Week 12 
Visit to subjects participating in the Dose-tapering Period), according to the subject’s 
assignment to a dose group and subject body weight recorded at the dispensing visit 
(Day -1 weight for Day 1 dispensing).   
 
Revised Text: 
Treatment Period and Dose-tapering Period 
Subjects will be administered 4.0% wt/vol oral suspension (Formulation route of 
synthesis 2 [ROS2]).   
The planned vamorolone doses are 2 mg/kg and 6 mg/kg daily. The initial patients 
enrolled in each age group will receive 2 mg/kg/day to confirm the PK and safety of 
vamorolone in both age groups at this dose level. After review of the PK and safety 
data from at least 6 patients in each age cohort, subsequent patients can be enrolled at 
the 6 mg/kg /day dose level. If the intended dose of vamorolone is 6 mg/kg/day, AND 
patients weigh 50 kg or more, the daily dose should be capped at 300mg. Considering 
the linearity of vamorolone pharmacokinetics, if the intended patient dose is 
2mg/kg/day, the dose is capped at 100mg per day for patients weighing 50kg or more.. 
All subjects: vamorolone 4.0% wt/vol oral suspension (investigational medicine) will 
be administered once daily over the 12-week Treatment Period (Weeks 1-12) and 
during the Dose-tapering Period, if applicable.   
 
 
Study Synopsis, Study Summary 
Original Text:  
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1.  For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit.  Study drug dosing will occur at home on all days except 

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dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when dosing will occur at 
the study site 
Revised Text: 
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day (for participants weighing 50kg and 
over, the dose is capped at 100mg/day) or 6.0 mg/kg/day (for participants weighing 
50kg and over, the dose is capped at 300mg/day), beginning the next day on Treatment 
Period Day 1.  For all subjects, daily study drug dosing during the Treatment Period 
will occur from the date of the Day 1 Visit through the date of the Week 12 Visit.  
Study drug dosing will occur at home on all days except dates of the Day 1, Week 2, 
Week 6, and Week 12 Visits, when dosing will occur at the study site. 
 
 
Study Synopsis, Safety Measures 
Original Text:  
Grading of clinical and clinical laboratory AEs will be according to the Common 
Terminology Criteria for Adverse Events (CTCAE), v.4.03 
Revised Text: 
Grading of clinical and clinical laboratory AEs will be according to the Common 
Terminology Criteria for Adverse Events (CTCAE), v5.0 
 
Study Synopsis, Statistical methods 
Original Text:  
Sample Size: 
For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a total of 
approximately 20 subjects in the 2 to <4 years age group will be enrolled with 
approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day).  A 
total of approximately 24 subjects in the 7 to <18 years age group will be enrolled with 
approximately 12 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day) 
and each dose level group stratified 1:1 by glucocorticoid treatment status at study 
entry to include approximately 6 subjects glucocorticoid-untreated and 6 subjects 
glucocorticoid-treated at study entry.  This sample size is considered sufficient to 
detect drug safety concerns in a pediatric population ages 2 to <4 and 7 to <18 years 
with DMD based on clinical judgment and prior study of vamorolone at these doses.  
In addition, this sample size is sufficiently large to determine PK parameters.   
 (…) 

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Pharmacodynamic Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover, as well as exploratory biomarkers of safety and efficacywill be assessed.   
 
Revised Text: 
Sample Size: 
This is an open-label, multiple dose study.  Study medication is administered daily in 
this Phase II trial.   
For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a total of 
approximately 20 subjects in the 2 to <4 years age group will be enrolled with 
approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day).  A 
total of approximately 34 subjects in the 7 to <18 years age group will be enrolled with 
approximately 12 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day) 
and each dose level group stratified 1:1 by glucocorticoid treatment status at study 
entry to include approximately 6 subjects glucocorticoid-untreated and 6 subjects 
glucocorticoid-treated at study entry, to which 10 subjects 12 to <18 years are added to 
the 6 mg/kg dose level.  This sample size is considered sufficient to detect drug safety 
concerns in a pediatric population ages 2 to <4 and 7 to <18 years with DMD based on 
clinical judgment and prior study of vamorolone at these doses.  In addition, this 
sample size is sufficiently large to determine PK parameters.   
(…) 
Pharmacodynamic Analyses: 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover, as well as exploratory biomarkers of safety and efficacy, including in the 
additional 12 to <18 years age group: suppression of the gonadal axis (LH, FSH) and 
suppression of the thyroid axis (TSH, FT4), will be assessed.   
 
1.1 Background and Unmet Need 
Original Text:  
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. 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. 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.  

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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. NF-κB has been shown to regulate the expression of numerous inflammatory 
genes in immune cells and muscle fibers, and the infiltration and activation of these 
cells can trigger muscle fiber death.  
Although significant advances have been made in understanding the etiology of DMD, 
a cure has not been found, and until recently treatment options were medications used 
“off- label” to alleviate the symptoms of DMD. Despite scientific advances, only 
glucocorticoids, such as prednisone or deflazacort, have consistently demonstrated 
efficacy in clinical trials. Indeed, the United States Food and Drug Administration (US 
FDA) recently approved deflazacort as a treatment for DMD. 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 
adverse effect profiles, often limiting long-term administration. A current goal of DMD 
research is to find a mutation-independent treatment that matches or exceeds the 
efficacy of glucocorticoids with a significantly lower adverse effect profile.  
Vamorolone is a first generation delta-9, 11 chemical compound belonging to the 
structural class of synthetic steroidal drugs, which includes the glucocorticoids 
prednisone, prednisolone, methylprednisolone, and dexamethasone. The chemical 
structure of vamorolone has optimized five subactivities of traditional glucocorticoid 
drugs, namely transactivation, transrepression, physiochemical membrane properties, is 
not a substrate for the corticosteroid modulatory 11β-hydroxysteroid dehydrogenase 
enzymes (11BHSD1, 11BHSD2), and is a potent mineralocorticoid receptor antagonist. 
Comparative structure/activity relationship studies using the active metabolites of 
prednisone, deflazacort, and vamorolone have demonstrated differential binding of 
vamorolone to the target glucocorticoid receptor, and downstream changes in 
pharmacodynamics.  By reducing transactivation subproperties, retaining 
transrepression, imparting membrane stabilizing properties, and inhibiting the 
mineralocorticoid receptor pathway, and lack of inactivation by 11β-hydroxysteroid 
dehydrogenase enzymes, vamorolone has favorable efficacy and adverse 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 data to date suggest that vamorolone may offer a 
much needed alternative to the current glucocorticoids which are standard of care for 
DMD with administration beginning around the age of 5 years in most developed 
countries, or even earlier in some cases.  

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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. The cumulative 
adverse 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. Glucocorticoids also contribute to further muscle damage 
with long-term administration. Vamorolone has shown few if any of the adverse effects 
of traditional glucocorticoids in mouse models of DMD.
This study is designed to explore, in DMD boys ages 2 to <4 years and 7 to <18 years, 
whether vamorolone will show similar efficacy to glucocorticoids with a more 
favorable adverse effect profile, thereby improving the quality of life for these DMD 
patients. This profile would enable use of vamorolone in DMD boys at a younger age 
than when glucocorticoid treatment is currently initiated. In addition, vamorolone 
could be prescribed in later stage non-ambulant young men with DMD and for a longer 
period of time, 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- B 
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. Further, vamorolone has been recently demonstrated to improve asynchronous 
remodeling, believed to be a component of progressive muscle weakness and wasting 
in DMD and may also prevent muscle membrane damage, thereby delaying 
progression of the disease further. 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. Finally, vamorolone imparts physical 
stability to myofiber plasma membranes, whereas prednisolone destabilizes 
membranes. This property addresses the primary defect of membrane instability in 
dystrophin deficient myofibers in DMD. 
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. 
Revised Text:
DMD is the most common childhood muscular dystrophy with a birth incidence 
worldwide of 1 in 3,600 to 9,300 males [Mah et al, 2014]. Clinical characteristics of 
DMD are proximal muscle weakness presenting in childhood and progressive 
involvement of most muscle groups, leading to loss of ambulation late in the first 
decade or early in the second decade of life. Weakness progresses, with the patient 
requiring assistance with the activities of daily living by the late teens or in their early 

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twenties. Patients with DMD often succumb from respiratory failure and/or cardiac 
failure.  
DMD is an X-linked recessive disorder caused by mutations in the DMD gene [Koenig 
1987] which codes for the dystrophin protein that provides structural stability to the 
dystrophin-associated glycoprotein complex on muscle cell membranes [Hoffman et al, 
1987]. The lack of dystrophin reduces plasma membrane stability, resulting in 
membrane fragility and necrosis [Evans et al, 2009].  
Upregulated inflammatory gene expression and activated immune cell infiltrates are 
present during early disease stages and play a significant role in muscle wasting [Chen 
et al, 2005]. The transcription factor NF-κB has been shown to regulate the expression 
of numerous inflammatory genes in immune cells and muscle fibers [Pahl, 1999; Dogra 
et al, 2006; Acharyya et al, 2007; Kumar et al, 2003] and the infiltration and activation 
of these cells can trigger muscle fiber death [Acharyya et al, 2007].  
GR agonists, such as prednisone and deflazacort [Malik et al, 2012] are currently the 
cornerstone for the treatment of patients with DMD according to American Academy 
of Neurology practice guidelines [Gloss et al, 2016] and the DMD Care Considerations 
Working Group [Birnkrant et al, 2018]. The benefits of long-term glucocorticoid 
therapy have been shown to include loss of ambulation at a later age, preserved upper 
limb and respiratory function, and avoidance of scoliosis surgery [Birnkrant et al, 
2018].  
The adverse effects of glucocorticoids include weight gain, cushingoid appearance, 
growth delay, behavior changes, an increased frequency of vertebral fractures, skin 
fragility, cataract, increased intra ocular pressure, adrenal suppression, insulin 
resistance [Kauh et al, 2012] and muscle atrophy [Schakman et al, 2013]. These 
adverse drug reactions (ADRs) negatively impact quality of life and cause considerable 
variation in clinical practice including suboptimal dosing [Griggs et al, 2013; Bello et 
al, 2015].  
The significant adverse effects of glucocorticoids on growth also prevent their routine 
administration in infants or toddlers, despite evidence that better outcomes are achieved 
with earlier administration [Merlini et al, 2012; Pane et al, 2014; Ciafaloni et al, 2016; 
Connolly et al, 2019; McMillan 2019; Buckon et al, 2022].  
There is therefore an ongoing need to develop glucocorticoids with a better safety 
profile. 
Rationale to develop vamorolone for DMD  
Preclinical and clinical studies have shown that vamorolone addresses the anti- 
inflammatory activity of the GR and avoids some of its unwanted effects such as 
growth stunting, inhibition of bone metabolism, and induction of neutrophilia.  
The anti-mineralocorticoid activity of vamorolone, as shown in the preclinical studies 
may be beneficial since the renin-angiotensin-aldosterone axis is thought to be 
involved in the pathogenesis of skeletal muscle fibrosis and cardiomyopathy in DMD 
[Rodriguez-Gonzalez et al, 2021; Howard et al, 2022].  

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In addition, the lack of activation/inactivation of vamorolone by 11-β-HSD 1 and 2 
may be an advantage since the pharmacological activity of prednisone, including some 
of its adverse effects such as osteoporosis, is linked to its local activation to 
prednisolone by 11- β-HSD 1 [Fenton et al, 2019; Morgan et al, 2014; Fenton et al, 
2021; Webster et al, 2021; Cooper et al, 2003].  
Lastly, the observed effect of cell membrane repair after injury in mice may be 
particularly relevant for dystrophin-deficient cells in DMD where plasma membranes 
are inherently unstable.  
Based on this differentiated profile, vamorolone has the potential to combine the 
known efficacy of glucocorticoids in DMD with a better safety profile.   
 
1.2 Nonclinical Experience Section  
Original Text:  
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.  
All Good Clinical Laboratory (GLP) studies were conducted in, or inspected by, a 
country that has implemented the Organisation for Economic Cooperation and 
Development (OECD) Mutual Acceptance of Data system.  
Revised Text: 
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. Refer to the current IB for updated 
information on the nonclinical experience of vamorolone.  
 
Sections 1.2.1. Safety Pharmacology, 1.2.2. Pharmacokinetics and metabolism, 
1.2.3 Toxicology  
Revised text: 
These sections are deleted and reference is made to the current IB version 
 
1.3 Clinical experience 
Original Text:  
Clinical experience with vamorolone is comprised of a completed Phase I clinical trial 
of vamorolone in healthy adult volunteers (VBP15-001), completed Phase IIa (VBP15-
002) and Phase II extension (VBP15-003) trials in DMD boys, completed Phase II 
long-term extension (VBP15-LTE) trial in DMD boys, and a completed Phase IIb 
active- and placebo-controlled trial in DMD boys (VBP15-004). Furthermore, two 

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relative bioavailability and food effect studies have been conducted (VBP15-PKFORM 
and VBP15-PKFORM-002) comparing the formulation used in clinical studies (ROS1) 
with the to-be-marketed formulation (ROS2).  
Revised Text: 
Clinical experience with vamorolone is comprised of a completed Phase I clinical trial 
of vamorolone in healthy adult volunteers (VBP15-001), completed Phase IIa (VBP15-
002) and Phase II extension (VBP15-003) trials in DMD boys, completed Phase II 
long-term extension (VBP15-LTE) trial in DMD boys, and a completed Phase IIb 
active- and placebo-controlled trial in DMD boys (VBP15-004).  Vamorolone is 
extensively metabolized in the liver hence the impact of an impaired hepatic function 
on vamorolone PK was assessed in a clinical study in adult volunteers with moderate 
impaired hepatic function [VBP15-HI].  [VBP15-DDI ] study  investigated  the  effect  
of  itraconazole  on  the  PK  of  on a single dose of vamorolone in healthy subjects. 
Furthermore, two relative bioavailability and food effect studies have been conducted 
(VBP15-PKFORM and VBP15-PKFORM-002) comparing the formulation used in 
clinical studies (ROS1) with the to-be-marketed formulation (ROS2).  
 
Section 1.3. All subsections (1.3.1. to 1.3.4.) 
Revised text: 
These sub-sections of 1.3. are deleted and reference is made to the current IB version 
 
1.4 Pharmacokinetics of Vamorolone 
New section. Rationale for study design, former Section 1.4., is moved to Section 1.6.. 
Revised text:  
The PK of vamorolone in subjects with DMD aged 4 to 7 years was thoroughly 
evaluated with intense PK sampling on Days 1 and 14 of daily vamorolone 
administration in Study VBK15-002.  Vamorolone peak plasma concentrations 
occurred on average 2 to 4 hours after dosing, exposure increased linearly with dose 
and the exposure after 6.0 mg/kg/day in terms of mean (SD) Cmax and AUC0-inf was 
970 (270) ng/mL and 3606 (897) ng.hr/mL, respectively on Day 14).  The mean (SD) 
t½ of vamorolone at 6.0 mg/kg/day was 1.4 (0.35) hours and no accumulation is 
observed with daily administration. 
The Population PK (PPK) evaluation based on PK data from studies VBP15-002 and 
VBP15-004 estimated the CL/F and V/F values for a typical DMD patient weighing 20 
kg and taking vamorolone with a meal as 58 L/hr and 162 L, respectively The PPK 
estimate vamorolone Tmax is 2.4 hours, the estimated elimination half-life in DMD 
boys is 1.9 hours and the calculated exposure at steady state after 6.0 mg/kg/day in 
terms of Cmax and AUC0-inf was 555 ng/mL and 2944 ng.hr/mL, respectively, in a 
typical DMD patient weighing 20 kg and taking vamorolone with a meal. 

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The results of the two bioavailability/food effect studies (VBP15-PK-FORM and 
VBP15-PK-FORM-002) support the change from the Clinical Formulation (ROS1) to 
the To-be-marketed Formulation (ROS2/fine). The To-be marketed Formulation 
(ROS2/fine) demonstrates a lower food effect than the Clinical Formulation (ROS1) 
and offers more reliable dosing (i.e., more consistent exposure) when taken with 
different types of food.  
Hepatic impairment increases the exposure to vamorolone. Subjects with moderate HI 
had 1.7 and 2.6-fold higher Cmax and AUC0inf values compared to age, weight and 
sex matched healthy adults  
The PK evaluation based on all 18 subjects showed no relevant increase in peak 
concentrations of vamorolone in the presence of the potent CYP3A4 inhibitor 
itraconazole, but AUC0-inf  increased  by  33.7%.  Median  Tmax  of  vamorolone  
was  2 hours  when  administered alone and was delayed when combined with 
itraconazole (4 hours). Thus, itraconazole has a weak effect on vamorolone PK. 
Refer to the current IB version for full and updated clinical pharmacology information 
 
1.5 Safety and Efficacy of Vamorolone in DMD (Study VBP-004) 
New section. Overall Benefit/Risk, former Section 1.5., is moved to Section 1.7.. 
Revised Text:  
The results of study VBP15-004, a randomized, double-blind, placebo controlled and 
prednisone referenced study showed that vamorolone produced clinically meaningful, 
statistically significant, and robust improvements in multiple measurements of lower 
limb motor function compared to placebo after 24 weeks of treatment. The 
improvements in motor function with vamorolone were similar to those seen with 
prednisone, a standard of care for children with DMD. The positive effects achieved at 
24 weeks with vamorolone 6 mg/kg remained stable over the course of the second 
period of the pivotal trial up to 48 weeks, both for patients who remained on 
vamorolone 6 mg/kg in both periods and for those who switched from prednisone 0.75 
mg/kg to vamorolone 6 mg/kg. Although the magnitude of effects on motor function in 
vamorolone 2 mg/kg was less well maintained over time, an improvement compared to 
baseline was still observed after 12 months. 
In study VBP15-004, a higher proportion of subjects presented with a least one TEAE 
in the vamorolone 2 and 6 mg/kg groups (83.3% and 89.3%, respectively) compared to 
placebo (79.3%) but in line with the prednisone 0.75 mg/kg group (83.9%). Clinically-
relevant TEAEs, pre-defined as moderate to severe events, SAEs, or events leading to 
discontinuation, were reported at similar rates in the placebo (31.0%) and vamorolone 
2 mg/kg groups (26.7%), less in the vamorolone 6 mg/kg group (14.3%), and more 
frequent in the prednisone 0.75 mg/kg group (41.9%). These results indicate that the 
increased proportion of subjects presenting with at least one TEAE in both of the 

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vamorolone groups compared to placebo was driven by an excess in mild TEAEs, 
while prednisone was also associated with an increase in moderate to severe events.   
Adverse Events of Special Interest, pre-defined as groupings of events typically 
associated with glucocorticosteroid therapy, were reported in a similar percentage of 
subjects in the placebo (69.0%) and vamorolone 2 mg/kg (66.7%) groups and higher 
percentages in the prednisone 0.75 mg/kg (77.4%) and vamorolone 6 mg/kg (78.6%) 
groups.  
The safety profile of vamorolone shares some risks with those described with 
glucocorticoids, such as 
x 
Vamorolone causes dose-dependent adrenal suppression. The level of adrenal 
suppression was slightly larger in vamorolone 6 mg/kg than prednisone 0.75 
mg/kg based on mean morning cortisol values, while the vamorolone 2 mg/kg 
had a partial effect.   
x 
Cushingoid features were frequently reported dose-dependent AEs with 
vamorolone. The incidence of cushingoid features were similar in vamorolone 6 
mg/kg and prednisone 0.75 mg/kg. Most of the events were reported as non-
clinically significant and did not lead to discontinuation of vamorolone.   
x 
Vamorolone 6 mg/kg was associated with an increase in BMI compared to 
placebo and comparable to the effect seen in prednisone 0.75 mg/kg. 
Vamorolone 2 mg/kg showed a less pronounced effect of limited clinical 
relevance.  
x 
Vamorolone 6 mg/kg was associated with an increased risk for behavioural 
problems, mainly mild irritability, which were more frequently reported in the 
first 6 months of treatment.   
x 
Gastrointestinal symptoms were reported at similar frequency than placebo over 
the first 6 months of treatment but showed evidence for dose-dependency over 
the long-term treatment suggestive of a drug effect.    
While the safety profile of vamorolone shares some risks with those described with 
glucocorticoids, it shows clinically relevant differences for a clinically improved safety 
profile in long-term therapy:  
x 
Absence of a deleterious effect on biomarkers of bone metabolism  
x 
Normal growth with any dose of vamorolone, supported by height z-scores 
similar to placebo at 6 months, remaining within the normal CDC growth 
curves at 12 months and in the long term in study VBP15-LTE, while evidence 
of growth stunting was already seen at Month 6 for the prednisone group. 
x 
A reduced frequency and severity of behavior related events on 6 mg/kg 
vamorolone compared with prednisone, while 2 mg/kg vamorolone was similar 
to placebo. 

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In addition, the findings of the vamorolone development programs suggests the 
potential for other differential effect in the long-term safety profile of vamorolone, 
such as: 
x 
Absence of a clinically relevant effect on glucose metabolism in study VBP15-
004 and over up to 30 months of treatment in study VBP15-002/002/LTE 
x 
Absence of an effect on neutrophil counts while neutrophilia was observed 
early after starting treatment with prednisone. 
x 
Absence of cases of cataracts or increase in intraocular pressure in studies 
VBP15-004 and VBP15-002/003/LTE  
Additional long-term data would be required to further characterize the risks. 
These data support a positive benefit-risk profile for vamorolone at the 2 mg/kg and 6 
mg/kg doses. The efficacy at the vamorolone 6 mg/kg dose is similar to current 
standard of care, prednisone, with an improved safety and tolerability profile compared 
to prednisone. The vamorolone 2 mg/kg shows robust efficacy compared to placebo at 
24 weeks and a further improved safety and tolerability profile compared to 
vamorolone 6 mg/kg and prednisone 0.75 mg/kg.  
Refer to the current IB version for full and updated clinical information.  
 
1.6 Rationale for study 
Original text 
1.4 Rationale for study 
The current Phase II study is designed to confirm the safe and tolerable dose(s) of 
vamorolone to be used to treat DMD in boys aged 2 to <4 years and 7 to <18 years, based 
upon safety and PK data, and to perform an exploratory evaluation of PD, clinical 
efficacy, behavior and neuropsychology, and physical functioning over a treatment period 
of 12 weeks.  Steroid-naïve subjects in the 2 to <4 years age group will be recruited for 
study, dictated by 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.  Enrollment of boys in the 7 to <18 years age group will be stratified to 
accommodate both glucocorticoid-treated and glucocorticoid-untreated subjects at time of 
study entry, to reflect real-world clinical experience with glucocorticoid treatment for 
DMD in older boys; analyses will be conducted separately for subjects in each 
glucocorticoid treatment group. 

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The vamorolone dose levels of 2.0 mg/kg/day and 6.0 mg/kg/day chosen for study have 
been shown to be safe and well-tolerated, and associated with improvements in muscle 
and strength assessments, in previous and ongoing vamorolone Phase II studies in boys 
4 to <7 years of age.  As a new route of synthesis of vamorolone, ROS2, will be used, 
boys will enroll into the 2.0 mg/kg/day group first, and drug exposure compared to 
previous ROS1 experience prior to enrolling into the higher 6.0 mg/kg/day dose group. 
Subjects who meet all eligibility criteria in this study (VBP15-006) will be assigned to 
one of six treatment groups as shown in Table 5. Groups 1, 3, and 4 will be fully enrolled 
at 2.0 mg/kg/day prior to assignment of subsequent participants to Groups 2, 5, and 6 at 
6.0 mg/kg/day. 
Table 5. 
Study Assignment Schedule 
Group 
Planned 
Number of 
Subjects 
Glucocorticoid 
Status 
Ages 2 to <4 Years 
Ages 7 to <18 Years  
1 
10 
Naïve* 
Vamorolone, 2.0 mg/kg/day 
 
2 
10 
Naïve* 
Vamorolone, 6.0 mg/kg/day 
 
3 
6 
Untreated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
4 
6 
Treated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
5 
6 
Untreated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
6 
6 
Treated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
*Naïve is defined as having had no prior glucocorticoid treatment for DMD, and past transient use of oral 
glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last 
use at least 3 months prior to enrollment, to be considered for enrollment on a case-by-case basis. 
Group 1 (age 2 to <4 years, vamorolone 2.0 mg/kg/day), Group 3 (age 7 to <18 years 
untreated at entry, vamorolone 2.0 mg/kg/day), and Group 4 (age 7 to <18 years treated at 
entry, vamorolone 2.0 mg/kg/day) will be fully enrolled prior to Groups 2, 5 and 6 (6.0 
mg/kg/day).   
(…) 
Pharmacodynamic safety biomarker findings in DMD patients receiving vamorolone 
2.0 mg/kg/day or 6.0 mg/kg/day over 12 weeks will be compared within each age group.  
Serum PD biomarkers bridged to later clinical safety concerns will be assessed over time 
as exploratory safety measures.  These PD biomarkers include: 
1. Adrenal suppression.  Pharmacological doses of glucocorticoids cause 
suppression of the hypothalamo-pituitary-adrenal axis, leading to low 

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concentration of endogenous cortisol and other steroidal hormones in serum.  
Adrenal suppression is directly associated with risk of adrenal crisis, delay of 
puberty and stunting of growth.  Measurement of morning cortisol concentrations 
will reflect the degree of adrenal suppression.  Plasma cortisol secretion typically 
follows a circadian pattern with the highest concentrations early in the morning; a 
morning serum cortisol concentration less than 3.6 μg/dL (or 100 nM) is highly 
suggestive of adrenal suppression.   
2. Bone turnover.  Pharmacological doses of glucocorticoids cause an imbalance of 
bone formation and bone resorption, leading to later osteopenia and bone 
fragility.  Bone fragility is a significant adverse effect of chronic pharmacologic 
glucocorticoids in DMD as this can lead to fracture, which increases the 
likelihood of premature loss of ambulation.  Serum biomarkers that have been 
bridged to later clinical outcomes of osteopenia are osteocalcin (bone formation; 
glucocorticoids decrease serum levels), aminoterminal propeptide of type I 
collagen (P1NP) (bone formation; glucocorticoids decrease serum levels), and 
CTX (bone resorption; glucocorticoids increase serum levels).  Decreases of 
osteocalcin and P1NP and increases of CTX are reflective of abnormal bone 
turnover, a risk factor bridged to later bone fragility. 
3. Insulin resistance.  Insulin resistance is the term where increased blood glucose 
triggers increased insulin secretion from the pancreatic islet cells, but the elevated 
serum insulin fails to sufficiently trigger glucose uptake by muscle and/or liver.  
Thus, peripheral tissues are resistant to insulin signaling (insulin resistance).  
Insulin resistance has been bridged to later clinical outcomes, including heart 
disease, type 2 diabetes, and vascular disease.  Serum biomarkers that are 
accepted as measures of insulin resistance are increased serum glucose and 
insulin.  This can be measured after acute (hours after first dose) or chronic (after 
weeks or months of dosing) glucocorticoid treatment. 
Additional exploratory safety outcomes are measures of additional serum safety 
biomarkers that have been defined in glucocorticoid-treated DMD and inflammatory 

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bowel disease patients.  Additional exploratory measures of efficacy include PD 
biomarkers that have previously been shown to be glucocorticoid-responsive in DMD 
boys, pediatric inflammatory bowel disease, adult vasculitis, and pediatric myositis.  
This trial will be conducted in compliance with this protocol, and in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki, and that are 
consistent with Good Clinical Practice (GCP) and the applicable regulatory requirements, 
and the issued FDA guidance on developing drugs for treatment for DMD and related 
dystrophinopathies.  
It is obligatory that the Investigator become familiar with all sections of the vamorolone 
Investigator’s Brochure.  
 
Revised Text 
1.6 Rationale for study 
The current Phase II study is designed to confirm the safe and tolerable dose(s) of 
vamorolone to be used to treat DMD in boys aged 2 to <4 years and 7 to <18 years, based 
upon safety and PK data, and to perform an exploratory evaluation of PD, clinical 
efficacy, behavior and neuropsychology, and physical functioning aover a treatment 
period of 12 weeks.  Steroid-naïve subjects in the 2 to <4 years age group will be 
recruited for study, dictated by 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.  Enrollment of boys in the 7 to <18 years age group will be stratified to 
accommodate both glucocorticoid-treated and glucocorticoid-untreated subjects at time of 
study entry, to reflect real-world clinical experience with glucocorticoid treatment for 
DMD in older boys; analyses will be conducted separately for subjects in each 
glucocorticoid treatment group. A group of 10 subjects is added to ensure a sufficient 
number of glucocorticoid-treated subjects 12 to <18 years of age are exposed to the 
higher dose (6 mg/kg). This change is introduced through protocol amendment #2 
because the 7 to <18 years of age group is recruiting a very limited number of these older 

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subjects. This imbalanced recruitment could potentially prevent objectives of the study to 
be met by not sufficiently exploring the 12 to <18 years age range. 
The vamorolone dose levels of 2.0 mg/kg/day and 6.0 mg/kg/day chosen for study have 
been shown to be safe and well-tolerated, and associated with improvements in muscle 
and strength assessments, in previous and ongoing vamorolone Phase II studies in boys 
4 to <7 years of age.  As a new route of synthesis of vamorolone, ROS2, will be used, 
boys will enroll into the 2.0 mg/kg/day group first, and drug exposure compared to 
previous ROS1 experience prior to enrolling into the higher 6.0 mg/kg/day dose group. 
Based on pharmacokinetics of vamorolone, the daily dose will be capped for the patients 
weighing 50 kg and above at 300mg in the 6mg/kg/day dose groups and 100mg in the 
2mg/kg/day dose groups. 
Subjects who meet all eligibility criteria in this study (VBP15-006) will be assigned to 
one of seven treatment groups as shown in Table 1. Groups 1, 3, and 4 will be fully 
enrolled at 2.0 mg/kg/day prior to assignment of subsequent participants to Groups 2, 5, 6 
and 7 at 6.0 mg/kg/day. 
Table 6. 
Study Assignment Schedule 
Group 
Planned 
Number of 
Subjects 
Glucocorticoid 
Status 
Ages 2 to <4 Years 
Ages 7 to <18 Years  
1 
10 
Naïve* 
Vamorolone, 2.0 mg/kg/day 
 
2 
10 
Naïve* 
Vamorolone, 6.0 mg/kg/day 
 
3 
6 
Untreated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
4 
6 
Treated at entry 
 
Vamorolone, 2.0 mg/kg/day/  
5 
6 
Untreated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
6 
6 
Treated at entry 
 
Vamorolone, 6.0 mg/kg/day/  
7 
10 
Treated at entry 
 
Vamorolone, 6.0 
mg/kg/day/  
*Naïve is defined as having had no prior glucocorticoid treatment for DMD, and past transient use of oral 
glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last 
use at least 3 months prior to enrollment, to be considered for enrollment on a case-by-case basis. 
Group 1 (age 2 to <4 years, vamorolone 2.0 mg/kg/day), Group 3 (age 7 to <18 years 
untreated at entry, vamorolone 2.0 mg/kg/day), and Group 4 (age 7 to <18 years treated at 
entry, vamorolone 2.0 mg/kg/day) will be fully enrolled prior to Groups 2, 5, 6 and 7 (6.0 
mg/kg/day).   

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(…) 
Pharmacodynamic safety biomarker findings in DMD patients receiving vamorolone 
2.0 mg/kg/day or 6.0 mg/kg/day over 12 weeks will be compared within each age group.  
Serum PD biomarkers bridged to later clinical safety concerns will be assessed over time 
as exploratory safety measures.  These PD biomarkers include: 
1. Adrenal suppression.  Pharmacological doses of glucocorticoids cause suppression 
of the hypothalamo-pituitary-adrenal axis, leading to low concentration of 
endogenous cortisol and other steroidal hormones in serum.  Adrenal suppression 
is directly associated with risk of adrenal crisis,.  Measurement of morning 
cortisol concentrations, 24 hr after the last dose,  will reflect the degree of adrenal 
suppression.  Plasma cortisol secretion typically follows a circadian pattern with 
the highest concentrations early in the morning; a morning serum cortisol 
concentration less than 3.6 μg/dL (or 100 nM) is highly suggestive of adrenal 
suppression.   
2. Bone turnover.  Pharmacological doses of glucocorticoids suppress  bone 
formation and bone resorption, leading to later osteopenia and bone fragility [van 
Staa et al. 2000]. Bone fragility is a significant adverse effect of chronic 
pharmacologic glucocorticoids in DMD as this can lead to fracture, especially 
vertebral fractures, which increases the likelihood of premature loss of 
ambulation.  Serum biomarkers that have been bridged to later clinical outcomes 
of osteopenia in adults are osteocalcin (bone formation; glucocorticoids decrease 
serum levels), aminoterminal propeptide of type I collagen (P1NP) (bone 
formation; glucocorticoids decrease serum levels), and CTX (bone resorption; 
glucocorticoids increase serum levels in adults 
3. Insulin resistance.  Insulin resistance has been bridged to later clinical outcomes, 
including heart disease, type 2 diabetes, and vascular disease.  Serum biomarkers 
that are accepted as measures of insulin resistance are increased serum glucose 
and insulin.  This can be measured after acute (hours after first dose) or chronic 
(after weeks or months of dosing) glucocorticoid treatment. 
Exploratory safety outcomes will be assessed  by  additional serum safety biomarkers that 
have been defined in glucocorticoid-treated DMD and inflammatory bowel disease 
patients.  Additional exploratory measures of efficacy include PD biomarkers that have 
previously been shown to be glucocorticoid-responsive in DMD boys, pediatric 
inflammatory bowel disease, adult vasculitis, and pediatric myositis.  
This trial will be conducted in compliance with this protocol, and in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki, and that are 
consistent with Good Clinical Practice (GCP) and the applicable Health Canada 

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regulatory requirements , and the issued FDA guidance on developing drugs for treatment 
for DMD and related dystrophinopathies [FDA 2015].  
 
 
1.7 Overall Benefit/Risk 
Original Text:  
1.5 Overall Benefit/Risk 
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. 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 were a total of 4 SAEs in the Phase II VBP15-003 study, three 
SAEs to date in the VBP15-LTE extension study, and one SAE to date in the VBP15-004 
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, one SAE of influenza- associated 
dehydration in a subject receiving 6.0 mg/kg/day, two SAEs of acute myoglobinuria in a 
subject receiving 6.0 mg/kg/day, and one SAE of viral gastroenteritis in a subject 
receiving blinded study drug, who was admitted to the hospital for dehydration. Each of 
these SAEs was considered unrelated to study drug, and none of them resulted in 
discontinuation from the study. 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. On the basis of mean GLDH and GGT data, vamorolone at dose levels 
up to 6.0 mg/kg/day did not appear to induce liver toxicity over a 24-week treatment 
period in the VBP15-003 study. In the VBP15-002 study, after 2 weeks of treatment, 0 of 
11 tested participants who received vamorolone 0.25 mg/kg/day, 0 of 11 tested 
participants who received vamorolone 0.75 mg/kg/day, 2 of 11 (18.2%) tested 
participants who received vamorolone 2 mg/kg/day, and 6 of 10 (60.0%) tested 
participants who received vamorolone 6 mg/kg/day had a depressed morning cortisol 
(<3.6 μg/dL [100 nmol/L]) consistent with chronic 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. 
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) and 
Manual of Operations, and Investigators should monitor clinical study participants closely 
to identify elevations in liver-specific enzymes. In the VBP15-004 double-blind, placebo- 
and prednisone-controlled study, a lower proportion of subjects in the Safety Population 
who experienced at least one TEAE during Treatment Period #1 was observed for 
subjects in the placebo group (79.3%) compared to subjects in the prednisone 0.75 

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mg/kg/day (83.9%), vamorolone 2.0 mg/kg/day (83.3%), and vamorolone 6.0 mg/kg/day 
(89.3%) groups: 23 subjects (79.3%) in the placebo group experienced a total of 77 
TEAEs; 26 subjects (83.9%) in the prednisone 0.75 mg/kg/day group experienced a total 
of 121 TEAEs; 25 subjects (83.3%) in the vamorolone 2.0 mg/kg/day group experienced 
a total of 97 TEAEs; and 25 subjects (89.3%) in the vamorolone 6.0 mg/kg/day group 
experienced a total of 91 TEAEs; a greater total number of TEAEs was experienced by 
subjects in the prednisone group (121), with fewer TEAEs experienced by subjects in the 
placebo (77), vamorolone 2.0 mg/kg/day (97), and vamorolone 6.0 mg/kg/day (91) 
groups (Table 6). A total of 51 subjects (43.2%) in the Safety Population experienced at 
least one treatment-related TEAE: eight subjects (27.6%) in the placebo group; 14 
subjects (45.2%) in the prednisone 0.75 mg/kg/day group; 10 subjects (33.3%) in the 
vamorolone 2.0 mg/kg/day group; and 19 subjects (67.9%) in the vamorolone 6.0 
mg/kg/day group. None of the treatment-related TEAEs was serious. One subject (3.2%) 
in the prednisone 0.75 mg/kg/day group reported a TEAE with CTCAE grade ≥ 3.  
One subject (3.2%) in the prednisone 0.75 mg/kg/day group experienced a TEAE leading 
to study drug and study discontinuation.  
One subject (3.3%) in the vamorolone 2.0 mg/kg/day group experienced one serious 
TEAE during Treatment Period #1 of the study.  
No subject experienced a TEAE considered by the Investigator to be life-threatening or 
which resulted in death during Treatment Period #1 of the study.  

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Potential Health Benefits: Subjects may or may not receive direct health benefit from 
participating in the study. Subjects will be assigned to vamorolone at one of two planned 
dose levels (2.0 mg/kg/day and 6.0 mg/kg/day) over the course of the 12-week trial. 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 the VBP15-004 double-blind study, both 
2.0 and 6.0 mg/kg/day vamorolone groups showed significant improvement vs. placebo 
on motor outcomes, and improvements were comparable to the prednisone group. In view 
of the initial clinical evidence of safety, the improvements observed in the assessments of 
efficacy, and the nature of potential adverse effects that can be monitored, the data 
support an acceptable benefit/risk profile for vamorolone.  
Revised Text: 
1.7 Overall Benefit/Risk 
Vamorolone has shown positive benefit-risk profile for both doses. The dose of 2mg/kg 
shows an even more favorable safety and tolerability profile as most of the vamorolone-
related risks were dose-dependent, still with evidence of efficacy, thus providing an 
alternative dose with a positive benefit-risk profile that could be considered for patients 
having tolerability concerns. At 6mg/kg dose , the efficacy is similar  to  current  standard  

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of  care,  prednisone,  with an improved safety and tolerability profile supporting its use 
as the recommended starting dose for the long-term treatment of DMD. Please refer to the 
current Investigator Brochure for more information.  
 
2.2.3 Exploratory Endpoints 
Original Text 
For each vamorolone dose level and age group, the following endpoints will be 
evaluated.  Additionally, for selected endpoints, subjects within the 7 to <18 years age 
group who were on glucocorticoid therapy at the time of assignment to a dose group 
may be evaluated separately from those who were off glucocorticoid therapy for at 
least 3 months prior to assignment to a dose group: 
 
Revised Text 
For each vamorolone dose level and age group, the following endpoints will be 
evaluated.  Additionally, for selected endpoints, subjects within the 7 to <18 years age 
group who were on glucocorticoid therapy at the time of assignment to a dose group 
may be evaluated separately from those who were off glucocorticoid therapy for at 
least 3 months prior to assignment to a dose group and also between subjects <12 years 
and subjects ≥ 12 years: 
 
 
2.2.4 Pharmacodynamic Endpoints 
Original Text 
For each vamorolone dose level and age group, the following pharmacodynamic 
biomarkers reflective of safety concerns of glucocorticoids will be evaluated. 
Additionally, subjects within the 7 to <18 years age group who were on glucocorticoid 
therapy at the time of assignment to a dose group may be evaluated separately from 
those who were off glucocorticoid therapy for at least 3 months prior to assignment:  
1. Adrenal suppression. First-in-morning serum cortisol levels will be 
measured.  Cortisol measures falling below 3.6 μg/dL (100 nM) will be 
considered to be indicative of the development of adrenal suppression;  
2. Bone turnover. Measures of serum osteocalcin and serum P1NP are reflective 
of bone formation, and measures of serum CTX are reflective of bone 
reabsorption. Ratios of osteocalcin and CTX predict later clinical safety 
concerns of osteopenia and bone fragility. Serum osteocalcin, serum CTX, and 
serum P1NP will be measured;  
3. Insulin resistance. Glucocorticoids cause both acute and chronic insulin 
resistance resistance, with serum elevations of both insulin and glucose. 

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Measures of hyperinsulinemia and hyperglycemia are accepted measures of 
insulin resistance. Fasting glucose and insulin, and hemoglobin A1c (HbA1c) 
will be measured;  
4. Exploratory biomarkers for aspects of safety and efficacy.  
 
Revised Text: 
For each vamorolone dose level and age group, the following pharmacodynamic 
biomarkers reflective of safety concerns of glucocorticoids will be evaluated.  
Additionally, subjects within the 7 to <18 years age group who were on glucocorticoid 
therapy at the time of assignment to a dose group may be evaluated separately from 
those who were off glucocorticoid therapy for at least 3 months prior to assignment: 
1. Adrenal suppression.  First-in-morning serum cortisol levels will be 
measured 24 hours after the last dose of vamorolone.  Cortisol measures falling 
below 2.4 μg/dL (66nM) for boys below 12 years  or 3.6 μg/dL (100 nM) for 
boys 12 years or older will be considered to be indicative of adrenal 
suppression 
2. Bone turnover.  Measures of serum osteocalcin and serum P1NP are reflective 
of bone formation, and measures of serum CTX are reflective of bone 
resorption.  Serum osteocalcin, serum CTX, and serum P1NP will be measured; 
3. Insulin resistance.  Glucocorticoids cause both acute and chronic insulin 
resistance with serum elevations of both insulin and sometimes glucose and 
HbA1c.  Measures of hyperinsulinemia and hyperglycemia are accepted 
measures of insulin resistance.  Fasting glucose and insulin, and hemoglobin 
A1c (HbA1c) will be measured; you can have insulin resistance with normal 
glucose values  
4. Exploratory biomarkers for aspects of safety and efficacy, including in the 
additional 12 to <18 years age group: suppression of the gonadal axis (LH, 
FSH) and suppression of the thyroid axis (TSH, FT4).  
 
3.1 Overall Study Design 
Original Text 
This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical 
functioning of vamorolone (the investigational medication) 2.0 mg/kg, and 6.0 mg/kg 
administered daily by liquid oral suspension over a treatment period of 12 weeks in 
steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated and currently 
untreated boys ages 7 to <18 years with DMD.   
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day 
Pretreatment Baseline Period; a 3-month open label Treatment Period (Weeks 112); 

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and a 4 week open label Dose-tapering Period (Week 13-16) for subjects who will not 
transition directly to further vamorolone or standard of care (SoC) glucocorticoid 
treatment at the end of the study  
Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent is obtained.   
Within the 2 to <4 years age group, the initial 10 eligible subjects will be assigned to 
the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  The subsequent 10 
eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline 
Day -1 Visit. 
Within the 7 to <18 years age group, both corticosteroid-treated and untreated, the 
initial 12 eligible subjects will be assigned to the 2.0 mg/kg/day treatment group at the 
Baseline Day -1 Visit.  The subsequent 12 eligible subjects will be assigned to the 6.0 
mg/kg/day treatment group at the Baseline Day -1 Visit. 
The first 6 subjects in each age group at 2.0 mg/kg will serve as the PK/safety run-in 
cohorts. PK assessments will be performed at Week 2 and, together with the safety 
assessment during the first 4 weeks of treatment, will be the basis to confirm whether 
2.0 and 6.0 mg/kg/day will be used in the subsequent patients or if a dose adjustment is 
needed to avoid over or under-exposure in patients for any of the two age groups. 
The 7 to <18 years age group will be further stratified by glucocorticoid treatment 
status at study entry, with assignment of subjects 1:1:1:1 to groups: 1. Glucocorticoid-
treated subjects, 2.0 mg/kg/day treatment group; 2. Glucocorticoid-treated subjects, 6.0 
mg/kg/day treatment group; 3. Glucocorticoid-untreated subjects 2.0 mg/kg/day 
treatment group; 4. Glucocorticoid-untreated subjects 6.0 mg/kg/day treatment group.  
Glucocorticoid-treated subjects in the 7 to <18 years age group will take their final 
dose of SoC glucocorticoid therapy for DMD on Baseline Day -1, within 24 hours 
prior to administration of the first dose of vamorolone study medication.   
All subjects  in both age group will begin their assigned vamorolone treatment on 
Treatment Period Day 1 and will continue to receive their assigned vamorolone 
treatment throughout the duration of the 3month- Treatment Period (Weeks 1-12).   
At the end of the 3-month Treatment Period (Week 12), subjects will be given the 
option to receive vamorolone in an expanded access or compassionate use program, if 
possible, or to transition to SoC treatment for DMD (may include glucocorticoids).  
Subjects completing VBP15-006 and enrolling directly into the expanded access or 
compassionate use program or transitioning directly to SoC glucocorticoid treatment 
will not need to taper their vamorolone dose prior to participation in the expanded 
access or compassionate use program or initiation of SoC glucocorticoid treatment.  
All subjects who will not transition directly to further vamorolone or SoC 
glucocorticoid treatment will begin a 4-week open label Dose-tapering Period during 
which the dose of study medication will be progressively reduced and discontinued.  
Revised text 

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This Phase II study is an open-label, multiple dose study to evaluate the safety, 
tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical 
functioning of vamorolone (the investigational medication) 2.0 mg/kg, and 6.0 mg/kg 
administered daily by liquid oral suspension over a treatment period of 12 weeks in 
steroid-naïve boys ages 2 to <4 years, and glucocorticoid-treated and currently 
untreated boys ages 7 to <18 years with DMD.   
The study is comprised of a 5-week Pretreatment Screening Period; a 1-day 
Pretreatment Baseline Period; a 3-month Treatment Period (Weeks 1 to 12); and up to 
8 weeks  for the Dose-tapering Period (for subjects who will not transition directly to 
further vamorolone or standard of care (SoC) glucocorticoid treatment at the end of the 
study  
Subjects will be enrolled into the study at the Screening Visit, at the time written 
informed consent is obtained.   
Within the 2 to <4 years age group, the initial 10 eligible subjects will be assigned to 
the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  The subsequent 10 
eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline 
Day -1 Visit. 
Within the 7 to <18 years age group (which is including an additional 12 to <18 years 
age group), both corticosteroid-treated and untreated, the initial 12 eligible subjects 
will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit.  
The subsequent 22 eligible subjects will be assigned to the 6.0 mg/kg/day treatment 
group at the Baseline Day -1 Visit. 
The first 6 subjects in each age group at 2.0 mg/kg will serve as the PK/safety run-in 
cohorts. PK assessments will be performed at Week 2 and, together with the safety 
assessment during the first 4 weeks of treatment, will be the basis to confirm whether 
2.0 and 6.0 mg/kg/day will be used in the subsequent patients or if a dose adjustment is 
needed to avoid over or under-exposure in patients for any of the two age groups. 
The 7 to <18 years age group will be further stratified by glucocorticoid treatment 
status at study entry, with assignment of subjects 1:1:1:1 to groups: 1. Glucocorticoid-
treated subjects, 2.0 mg/kg/day treatment group; 2. Glucocorticoid-treated subjects, 6.0 
mg/kg/day treatment group; 3. Glucocorticoid-untreated subjects 2.0 mg/kg/day 
treatment group; 4. Glucocorticoid-untreated subjects 6.0 mg/kg/day treatment group. 
An additional group of 10 glucocorticoid-treated 12 to <18 years subjects will be 
assigned to the 6 mg/kg/day treatment.  Glucocorticoid-treated subjects in the 7 to <18 
years age group will take their final dose of SoC glucocorticoid therapy for DMD on 
Baseline Day -1, within 24 hours prior to administration of the first dose of 
vamorolone study medication.   
All subjects will begin their assigned vamorolone treatment on Treatment Period Day 
1 and will continue to receive their assigned vamorolone treatment throughout the 
duration of the 3month- Treatment Period (Weeks 1-12).   
At the end of the 3-month Treatment Period (Week 12), subjects will be given the 
option to receive vamorolone in an expanded access or compassionate use program, if 

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possible, or to transition to SoC treatment for DMD (may include glucocorticoids).  
Subjects completing VBP15-006 and enrolling directly into the expanded access or 
compassionate use program or transitioning directly to SoC glucocorticoid treatment 
will not need to taper their vamorolone dose prior to participation in the expanded 
access or compassionate use program or initiation of SoC glucocorticoid treatment.  
All subjects who will not transition directly to further vamorolone or SoC 
glucocorticoid treatment will begin the Dose- Period during which the dose of study 
medication will be progressively reduced and discontinued.  
 
3.2 Study Summary 
Original Text 
(…) 
A total of approximately 24 subjects ages 7 to <18 years will be assigned to receive 
vamorolone 2.0 mg/kg/day (glucocorticoid-untreated at study entry), 2.0 mg/kg/day 
(glucocorticoid-treated at study entry), 6.0 mg/kg/day (glucocorticoid-untreated at 
study entry), or 6.0 mg/kg/day (glucocorticoid-treated at study entry) (n=6 per dose 
level and glucocorticoid treatment status group).  The dose cohort of 2.0 mg/kg/day 
will be enrolled first and the PK and safety assessment from the first 6 subjects in this 
age group will be used to confirm the doses for the subsequent subjects following the 
same process as described for the younger age range. A total of approximately 44 
subjects will be enrolled into the study as shown in Table 5.  
The study is comprised of a Pretreatment Screening Period of up to 32 days duration, a 
1 day Pretreatment Baseline Period, a 12 week Treatment Period, and a 4 week Dose 
tapering Period (for subjects not continuing directly with further Vamorolone 
treatement or transitioning directly to SoC glucocorticoid treatment) Subject will be 
enrolled into this study at the time written informed consent is given, and assigned to 
treatment only after completion of all Pretreatment Screening assessments. 
Subjects will be assessed for safety and tolerability, PK, PD, clinical efficacy, behavior 
and neuropsychology, and physical functioning at scheduled visits throughout the 
study (see Section 6 for a schedule of study assessments).  Screening assessments will 
be performed prior to assignment to a dose group.  All subjects will be assigned to 
treatment at the Baseline Day -1 Visit.   
After completion of Screening and Baseline assessments, and assignment to a dose 
group for treatment, subjects  in both age group will return to the study clinic on Day 1 
for safety, PK, and PD assessments prior to administration of the first dose of study 
medication.  Additional study visits will occur at Week 2, Week 6, and Week 12.   
Adverse events, including serious adverse events (SAEs), and concomitant 
medications will be recorded throughout the study.  A Data and Safety Monitoring 
Board (DSMB) will review SAEs and other pertinent safety data at regular intervals 
during the study and make recommendations to the Sponsor regarding study conduct.   

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Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1. For all subjects in both age groups, daily study drug 
dosing during the Treatment Period will occur from the date of the Day 1 Visit through 
the date of the Week 12 Visit (see Section 5.3).  Study drug dosing will occur at home 
on all days except dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when 
dosing will occur at the study site.  
Revised text 
(…) 
A total of approximately 34 subjects ages 7 to <18 years will be assigned to receive 
vamorolone 2.0 mg/kg/day (glucocorticoid-untreated at study entry), 2.0 mg/kg/day 
(glucocorticoid-treated at study entry), 6.0 mg/kg/day (glucocorticoid-untreated at 
study entry), or 6.0 mg/kg/day (glucocorticoid-treated at study entry) (n=6 per dose 
level and glucocorticoid treatment status group plus n=10 for the additional 12 to <18 
years age group [6.0 mg/kg/day - glucocorticoid-treated]).  The dose cohort of 2.0 
mg/kg/day will be enrolled first and the PK and safety assessment from the first 6 
subjects in this age group will be used to confirm the doses for the subsequent subjects 
following the same process as described for the younger age range.Subjects will be 
assessed for safety and tolerability, PK, PD, clinical efficacy, behavior and 
neuropsychology, and physical functioning at scheduled visits throughout the study 
(see Section 6 for a schedule of study assessments).  Screening assessments will be 
performed prior to assignment to a dose group.  All subjects will be assigned to 
treatment at the Baseline Day -1 Visit.   
After completion of Screening and Baseline assessments, and assignment to a dose 
group for treatment, subjects will return to the study clinic on Day 1 for safety, PK, 
and PD assessments prior to administration of the first dose of study medication.  
Additional study visits will occur at Week 2, Week 6, and Week 12.   
The dose cohort of 2.0 mg/kg/ will be enrolled first and the PK of vamorolone after 2 
weeks of treatment and the safety of vamorolone during the first week of 
administration from the first 6 subjects in this age group will be used to confirm the 
doses for the subsequent subjects following the same process as described for the 
younger age range. 
If the vamorolone exposure at 2.0 mg/kg in the initial 6 patients of this age group 
deviates substantially from the target or if unexpected safety signals are observed, the 
high doses level for vamorolone for the subsequent subjects may be adjusted.  
Adverse events, including serious adverse events (SAEs), and concomitant 
medications will be recorded throughout the study.  A Data and Safety Monitoring 
Board (DSMB) will review SAEs and other pertinent safety data at regular intervals 
during the study and make recommendations to the Sponsor regarding study conduct.   
If the intended dose of vamorolone is 6mg/kg, but patients weigh 50 kg or more, the 
daily dose should be capped at 300mg/day. Considering the linearity of vamorolone 

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pharmacokinetics, if the patient is dosed at 2mg/kg, the dose is capped at 100mg daily 
for patients weighing 50 kg and above.  
Glucocorticoid-treated subjects in the 7 to <18 years age group will receive their final 
dose of SoC glucocorticoid treatment for DMD on Baseline Day -1 and switch to their 
assigned vamorolone treatment, 2.0 mg/kg/day or 6.0 mg/kg/day, beginning the next 
day on Treatment Period Day 1. For all subjects, daily study drug dosing during the 
Treatment Period will occur from the date of the Day 1 Visit through the date of the 
Week 12 Visit (see Section 5.3).  Study drug dosing will occur at home on all days 
except dates of the Day 1, Week 2, Week 6, and Week 12 Visits, when dosing will 
occur at the study site.  
 
3.3 Dose group assignment 
Original Text 
 (…) 
Similarly, subjects in the 7 to <18 years age group will be assigned to the 2.0 
mg/kg/day treatment groups first, then subsequently assigned to the planned 6.0 
mg/kg/day treatment groups. A total of approximately 24 subjects ages 7 to <18 years 
will be assigned 1:1:1:1 to receive vamorolone 2.0 mg/kg/day (glucocorticoid-
untreated at study entry), 2.0 mg/kg/day (glucocorticoid-treated at study entry), 6.0 
mg/kg/day (glucocorticoid-untreated at study entry), or 6.0 mg/kg/day (glucocorticoid-
treated at study entry) (n=6 per dose level and glucocorticoid treatment status group). 
Revised Text 
(…) 
Similarly, subjects in the 7 to <18 years age group will be assigned to the 2.0 
mg/kg/day treatment groups first, then subsequently assigned to the planned 6.0 
mg/kg/day treatment groups. A total of approximately 34 subjects ages 7 to <18 years 
will be assigned 1:1:1:1 to receive vamorolone 2.0 mg/kg/day (glucocorticoid-
untreated at study entry), 2.0 mg/kg/day (glucocorticoid-treated at study entry), 6.0 
mg/kg/day (glucocorticoid-untreated at study entry), or 6.0 mg/kg/day (glucocorticoid-
treated at study entry) (n=6 per dose level and glucocorticoid treatment status group 
plus n=10 for the additional 12 to <18 years age group [6.0 mg/kg/day - 
glucocorticoid-treated]). 
 
4.3 Exclusion Criteria 
Original Text 
 [….] 

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Note: Any parameter/test may be repeated at the Investigator’s discretion during 
Screening to determine reproducibility.  In addition, subjects may be rescreened if 
ineligible due to negative anti-varicella IgG antibody test result  
Revised Text 
 [….] 
Note: Any parameter/test may be repeated at the Investigator’s discretion during 
Screening to determine reproducibility.  In addition, subjects may be rescreened if 
ineligible due to negative anti-varicella IgG antibody test result after vaccination has 
been completed  Subjects may be rescreened in case of ongoing medical condition 
developing during the screening period, e.g. acute viral infection, or laboratory 
abnormality that could affect safety if the subject would start vamorolone. In this case, 
the subject can be rescreened after resolution of the medical condition. 
 
5.1 Study Medication Administered 
Original Text 
Planned vamorolone dose levels:2.0 mg/kg/day and 6.0 mg/kg/day. Doses can be 
adjusted based on PK and safety data from the first 6 patients per age group to avoid 
over- or under exposure and to achieve a consistent vamorolone AUC across the entire 
pediatric age range.  
Vamorolone will be administered to all subjects as an oral liquid suspension. 
A total of approximately 10 subjects in the 2 to <4 years age group will be enrolled 
into the 2.0 mg/kg/day treatment group.  After the pharmacokinetics and safety is 
determined in the initial 6 subjects and the doses are confirmed, enrollment will 
continue for 10 subjects in the 2 to <4 years age group into the planned 6.0 mg/kg/day 
treatment group.  
A total of approximately 12 subjects in the 7 to <18 years age group will be enrolled 
into the 2.0 mg/kg/day treatment groups (6 untreated at entry, 6 corticosteroid-treated 
at entry).  After the pharmacokinetics and safety is determined in the initial 6 subjects 
and the doses are confirmed, enrollment will continue for 12 subjects in the 7 to <18 
years age group into the planned 6.0 mg/kg/day treatment group.  
Revised Text 
Planned vamorolone dose levels:2.0 mg/kg/day and 6.0 mg/kg/day. Doses can be 
adjusted based on PK and safety data from the first 6 patients per age group to avoid 
over- or under exposure and to achieve a consistent vamorolone AUC across the entire 
pediatric age range. The recommended dose of vamorolone is 6 mg/kg once daily in 
patients weighing less than 50 kg. In patients weighing 50 kg and above, the high dose 
level (6 mg/kg once daily) must be capped at 300 mg once daily and the low dose level 
(2mg/kg/day) must be capped at 100 mg once daily.  

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Vamorolone will be administered to all subjects as an oral liquid suspension. 
A total of approximately 10 subjects in the 2 to <4 years age group will be enrolled 
into the 2.0 mg/kg/day treatment group.  After the pharmacokinetics and safety is 
determined in the initial 6 subjects and the doses are confirmed, enrollment will 
continue for 10 subjects in the 2 to <4 years age group into the planned 6.0 mg/kg/day 
treatment group.  
A total of approximately 12 subjects in the 7 to <18 years age group will be enrolled 
into the 2.0 mg/kg/day treatment groups (6 untreated at entry, 6 corticosteroid-treated 
at entry).  After the pharmacokinetics and safety is determined in the initial 6 subjects 
and the doses are confirmed, enrollment will continue for 22 subjects in the 7 to <18 
years age group into the planned 6.0 mg/kg/day treatment group (6 untreated at entry, 
6 corticosteroid-treated at entry plus 10 for the additional 12 to <18 years age group 
(glucocorticoid-treated).  
 
5.4 Rationale for Dose Selection 
Original text 
 (…) 
The results of the VBP15-004 24-week double-blind, placebo- and prednisone-
controlled study showed that doses of vamorolone 2.0 mg/kg/day and 6.0 mg/kg/day 
showed significant enhancement of muscle strength, mobility, and functional exercise 
capacity vs. placebo.  This study showed that doses of vamorolone 2.0 mg/kg/day and 
6.0 mg/kg/day did not cause the stunting of growth and deleterious changes in bone 
biomarkers seen with prednisone in this head-to-head comparison. 
Based on the safety and efficacy results observed in these earlier studies in DMD boys 
aged 4 to 7 years, doses of vamorolone at 2.0 mg/kg/day and 6.0 mg/kg/day were 
chosen for evaluation in the current study enrolling younger and older subjects. Since 
the effect of age on the pharmacokinetics of vamorolone is not yet established and 
since this is the first time that the to-be-marketed formulation of ROS2 will be 
administered to DMD boys, a PK/safety run-in at 2.0 mg/kg/day is included into the 
study to evaluate the PK and safety in subjects 2 to <4 and 7 to <18 years of age and to 
adjust the doses if needed to avoid over- and underexposure of vamorolone in these 
age groups and to ensure a consistent vamorolone AUC across the entire pediatric age 
range.  All doses of vamorolone will be administered in the morning with breakfast.   
 
Revised Text 
 (…) 
The results of the VBP15-004 24-week double-blind, placebo- and prednisone-
controlled study showed that doses of vamorolone 2.0 mg/kg/day and 6.0 mg/kg/day 
showed significant enhancement of muscle strength, mobility, and functional exercise 

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capacity vs. placebo.  This study showed that doses of vamorolone 2.0 mg/kg/day and 
6.0 mg/kg/day did not cause the stunting of growth and deleterious changes in bone 
biomarkers seen with prednisone in this head-to-head comparison. Additional efficacy 
and safety results can be found in the current IB.  
Based on the safety and efficacy results observed in these earlier studies in DMD boys 
aged 4 to 7 years, doses of vamorolone at 2.0 mg/kg/day and 6.0 mg/kg/day were 
chosen for evaluation in the current study enrolling younger and older subjects. For the 
6 mg/kg, a cap dose of 300 mg once daily has been established for children weighing 
more than 50 kg based on pharmacokinetic modeling to account for the expected high 
pharmacokinetic exposures due to growth and maturation of the pediatric population. 
Since the effect of age on the pharmacokinetics of vamorolone is not yet established 
and since this is the first time that the to-be-marketed formulation of ROS2 will be 
administered to DMD boys, a PK/safety run-in at 2.0 mg/kg/day is included into the 
study to evaluate the PK and safety in subjects 2 to <4 and 7 to <18 years of age and to 
adjust the doses if needed to avoid over- and underexposure of vamorolone in these 
age groups and to ensure a consistent vamorolone AUC across the entire pediatric age 
range.  All doses of vamorolone will be administered in the morning with breakfast.   
 
 
5.6 Study Drug Dose Interruption or Discontinuation 
Original text 
 (…) 
In the event any clinical observation suggests an intolerability of an individual subject 
to the study medication, in the opinion of the Investigator, the case should be discussed 
with the Study Chair and Medical Monitor within 24 hours and study drug 
discontinuation should be considered.  In view of the potential effect of the study drugs 
on adrenal glands, the study drugs cannot be discontinued suddenly.  In case study 
drug needs to be discontinued, for whatever reason, the dose tapering process 
described for the end of the treatment period should be followed.  If a subject 
discontinues study drug due to intolerability, the subject will be withdrawn from the 
study.  The subject should return to the study site for completion of Week 12 
assessments at the time of early withdrawal, prior to participation in the Dose-tapering 
Period, as appropriate.  Any AE still ongoing at the time of study drug discontinuation 
will be monitored until it has returned to baseline status, stabilized, or the Investigator, 
Study Chair, Medical Monitor and Sponsor agree that follow-up is no longer needed.  
 
Revised Text 
 (…) 
In the event any clinical observation suggests an intolerability of an individual subject 
to the study medication, in the opinion of the Investigator, the case should be discussed 

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with the Medical Monitor within 24 hours and study drug discontinuation should be 
considered.  In view of the potential effect of the study drugs on adrenal glands, the 
study drugs cannot be discontinued suddenly.  In case study drug needs to be 
discontinued, for whatever reason, the dose tapering process described for the end of 
the treatment period should be followed.  If a subject discontinues study drug due to 
intolerability, the subject will be withdrawn from the study.  The subject should return 
to the study site for completion of Week 12 assessments at the time of early 
withdrawal, prior to participation in the Dose -tapering Period, as appropriate.  Any 
AE still ongoing at the time of study drug discontinuation will be monitored until it has 
returned to baseline status, stabilized, or the Investigator and Sponsor agree that 
follow-up is no longer needed.  
 
 
6.1 Time and Events Schedule 
Original Text 
 (…) 
x Dose-tapering Period: The 4-week interval following the end of the 12-week 
Treatment Period during which subjects who will not transition directly to further 
vamorolone or SoC glucocorticoid treatment will begin a 4week  open label Dose 
tapering- Period during which the dose of study medication will be progressively 
reduced and discontinued (see Section 6.3.5).  Subjects will be discharged from the 
study following completion of all final Dose-tapering Period assessments 
(…) 

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BL = Baseline; d = day(s); SCR = Screening.  
a) Only subjects who will not transition directly to further vamorolone or SoC glucocorticoid treatment 
at the end of the 12-week Treatment Period will begin a 4-week open-label Dose-tapering Period during 
which the dose of study medication will be progressively reduced and discontinued.  
b) All Day -1 assessments must be completed within 24 hours prior to administration of the first dose of 
study medication on Day 1.  
c) Time windows around the Week 2, Week 6, and Week 12 Visits are allowances from date of Day 1 
Visit; time window around Week 16 Visit is allowance from date of Week 12 Visit.  
d) Subjects who prematurely discontinue from the study prior to Week 12 should complete the Week 12 
assessments at the time of early withdrawal and undergo Dose-tapering, where appropriate.  
e) Subjects will have one study site visit during the Dose-tapering Period, at one week after the dose of 
study medication has been discontinued (Week 16).  
f) Subjects are considered to be enrolled in the study at the time written informed consent is obtained.  
g) Assignment to a treatment group is done by the TRiNDS Study Coordinator at the Baseline Day -1 
Visit.  
h) Standing height will be measured for subjects in the 2 to <4 years age group and participants ages 7 
to <18 years who can stand independently; ulnar length will be measured and used to calculate height 
for subjects in the 7 to <18 years age group.  
i) Sitting blood pressure, body temperature, respiratory rate, and heart rate.  
j) Vital signs recorded prior to administration of the first dose of study drug at the Day 1 Visit.  

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k) Blood for hematology, chemistry, and lipids. All samples should be collected after subject has fasted 
for >6 hours.  
l) Blood samples collected after subjects have fasted for ≥ 6 hours, and prior to daily dose of study 
drug.  
m) Urinalysis by dipstick and microscopic analysis.  
n) Blood collected for PD biomarkers includes exploratory safety outcomes of bone turnover 
(osteocalcin, CTX, P1NP) at Day 1 pre-dose and Week 12 pre-dose. Blood remaining from collected 
blood samples not needed for protocol-specified analyses may be stored for future exploratory 
biomarker studies for aspects of safety and efficacy. All pre-dose samples should be collected after 
subject has fasted for ≥ 6 hours.  
o) Blood collected for morning cortisol should be collected before 10 AM local time.  
p) Blood samples for population PK analysis will be collected within 30 minutes pre-dose and at 1, 2, 
and 6 hours post-dose at the Day 1 and Week 2 Visits (ages 2 to <4 years), and within 30 minutes pre-
dose, and at 1, 2, 4, 6 and 8 hours post-dose at the Day 1 and Week 2 Visits (ages 7 to <18 years).  
q) 12-lead ECG recorded after subject has rested quietly in a supine position for at least 5 minutes.  
r) Only for subjects participating in the Dose-tapering Period.  
s) Study medication brought by subjects to the Week 2 Visit for dosing and compliance assessment will 
be redispensed to subjects at the end of the visit.  
t) During the Treatment Period, the dose of study medication on the days of the Day 1, Week 2, Week 
6, and Week 12 Visits will be administered with breakfast in the study clinic. All other doses will be 
taken with breakfast at home.  
u) Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to ensure that the 
study drug tapering is proceeding according to protocol, to assess potential signs or symptoms indicative 
of adrenal suppression, and to address any questions the parent(s)/guardian(s) may have.  
v) Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale will be 
completed for subjects in the 2 to <4 years age group only.  
w) Performance of Upper Limb (PUL) test will be performed by subjects in the 7 to <18 years age group 
only.  
x) Ease of Study Medication Administration Assessment will be completed for subjects in the 2 to <4 
years age group only.  
y) Study Medication Acceptability Assessment will be completed by subjects in the 7 to <18 years age 
group only.  
z) Subject diaries used to record any changes in concomitant medications taken, any AEs experienced 
during the study, and any incomplete or missed doses of study medication.  
aa) All AEs and SAEs must be recorded in the source documents and eCRF from the date of the 
subject’s written informed consent until the final Week 16 Visit or the subject’s participation in the 
study is completed (SAEs through 30 days after final dose study drug). Ongoing AEs will be followed to 
resolution, stabilization, or until such time the Investigator believes follow-up is not necessary.  
bb)For subjects who do not continue into an expanded access or compassionate use program, site staff 
will make a phone call to the home 31-35 days after the final dose of study medication in VBP15 006 
Dose-tapering Period to confirm the final SAE status of the subject. 
cc) Subjects who elect to continue vamorolone therapy by enrolling directly into an expanded access or 
compassionate use program or who will transition directly to SoC glucocorticoid therapy may be 
discharged from the study following completion of all final Week 12 assessments. 

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dd)Subjects who participate in the Dose-tapering Period may be discharged from the study following 
completion of all final Dose-tapering Visit assessments (Week 16). 
Revised Text 
 (…) 
x Dose-tapering Period: The interval following the end of the 12-week Treatment Period 
during which subjects who will not transition directly to further vamorolone or SoC 
glucocorticoid treatment will begin a Dose tapering- Period during which the dose of 
study medication will be progressively reduced and discontinued (see Section 6.3.5).  
Subjects will be discharged from the study following completion of all final Dose-
tapering Period assessments 
(…) 
Table 2. 
Schedule of Study Activities 
 
 
Pretreatment Period 
 
Treatment Period 
Dose-tapering 
Perioda 
 
SCR 
BL 
 
 
 
Day 
Week 
Study Day or 
Week/Visit 
-33 to -2 
-1b 
Day 1b 
2c 
(±1d) 
6c 
(±3d) 
12c,d 
(±5d) 
14 
 
16c,d,e 
(±1d) 
Informed consent 
X 
 
 
 
 
 
 
 
Enrollmentf 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
Assignmentg 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Medication history 
X 
X 
 
 
 
 
 
 
Physical examination 
X 
Xee 
 
 
X 
X 
 
X 
Cushingoid features 
X 
X 
 
 
X 
X 
 
X 
Heighth 
X 
 
 
 
 
X 
 
 
Weight 
X 
X 
 
X 
X 
X 
 
X 
Vital signsi 
X 
X 
Xj 
X 
X 
X 
 
X 
Blood for clinical 
labsk 
X 
 
Xl 
 
Xl 
Xl 
 
X 
Blood for vitamin D 
X 
 
 
 
 
Xl 
 
 
Confirmation of 
varicella immunity 
X 
 
 
 
 
 
 
 
Urinalysism 
X 
 
X 
 
X 
X 
 
X 
Blood for serum PD 
biomarker paneln 
 
 
Xl 
 
 
Xl 
 
 
Fasting blood for 
insulin, glucose 
 
 
Xl 
Xl 
Xl 
Xl 
 
 
Blood for HbA1c 
X 
 
 
 
 
Xl 
 
 

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Blood for morning 
cortisolo 
 
 
Xl 
 
 
Xl 
 
 
Blood for Plasma PK 
 
 
Xp 
Xp 
 
 
 
 
12-lead ECGq 
X 
 
 
 
 
X 
 
 
Eye examination 
X 
 
 
 
 
X 
 
 
Dispense study 
medication 
 
 
X 
 
X 
Xr 
 
 
Return study 
medication/ 
compliance 
monitoring 
 
 
 
Xs 
X 
X 
 
X 
Study medication 
dosingt 
 
 
X 
 
 
X 
 
 
Study medication 
dose tapering 
 
 
 
 
 
Xr 
 
X 
Telephone call to 
subject 
 
 
 
 
 
 
Xu 
 
Bayley-III Gross 
Motorv 
X 
X 
 
 
 
X 
 
 
PUL Testw 
X 
X 
 
 
 
X 
 
 
Pediatric Outcomes 
Data Collection 
Instrument (PODCI) 
X 
 
 
 
 
X 
 
 
PARS III 
X 
 
 
 
 
X 
 
 
Ease of Study 
Medication 
Administration 
Assessmentx 
 
 
 
 
X 
X 
 
 
Study Medication 
Acceptability 
Assessmenty 
 
 
 
 
X 
X 
 
 
Dispense subject 
diariesz 
 
 
X 
X 
X 
Xq 
 
 
Return subject diaries 
 
 
 
X 
X 
X 
 
X 
AE/SAE recordingaa 
X 
 
 
 
 
 
 
Xbb 
Prior/Concomitant 
medications 
X 
 
 
 
 
 
 
X 
Discharge from study 
 
 
 
 
 
Xcc 
 
Xdd 
BL = Baseline; d = day(s); SCR = Screening.  
a) Only subjects who will not transition directly to further vamorolone or SoC glucocorticoid treatment at the end 
of the 12-week Treatment Period will begin a Dose-tapering Period during which the dose of study medication will 
be progressively reduced and discontinued.  
b) All Day -1 assessments must be completed within 24 hours prior to administration of the first dose of study 
medication on Day 1.  
c) Time windows around the Week 2, Week 6, and Week 12 Visits are allowances from date of Day 1 Visit; time 
window around Week 16 Visit is allowance from date of Week 12 Visit.  
d) Subjects who prematurely discontinue from the study prior to Week 12 should complete the Week 12 
assessments at the time of early withdrawal and undergo Dose-tapering, where appropriate.  
e) Subjects will have one study site visit during the Dose-tapering Period, at one week after the dose of study 
medication has been discontinued (Week 16).  
f) Subjects are considered to be enrolled in the study at the time written informed consent is obtained.  

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g) Assignment to a treatment group is done by the TRiNDS Study Coordinator at the Baseline Day -1 Visit.  
h) Standing height will be measured for subjects in the 2 to <4 years age group and participants ages 7 to <18 
years who can stand independently; ulnar length will be measured and used to calculate height for subjects in the 7 
to <18 years age group.  
i) Sitting blood pressure, body temperature, respiratory rate, and heart rate.  
j) Vital signs recorded prior to administration of the first dose of study drug at the Day 1 Visit.  
k) Blood for hematology, chemistry, and lipids. All samples should be collected after subject has fasted for >6 
hours.  
l) Blood samples collected after subjects have fasted for ≥ 6 hours, and prior to daily dose of study drug.  
m) Urinalysis by dipstick and microscopic analysis.  
n) Blood collected for PD biomarkers at Day 1 pre-dose and Week 12 predose includes exploratory safety 
outcomes of bone turnover (osteocalcin, CTX, P1NP, as well as in the additional 12 to <18 years age group, 
suppression of the gonadal axis (LH, FSH) and suppression of the thyroid axis (TSH, FT4). Blood remaining from 
collected blood samples not needed for protocol-specified analyses may be stored for future exploratory biomarker 
studies for aspects of safety and efficacy. All pre-dose samples should be collected after subject has fasted for ≥ 6 
hours.  
o) Blood collected for morning cortisol should be collected before 10 AM local time.  
p) Blood samples for population PK analysis will be collected within 30 minutes pre-dose and at 1, 2, and 6 hours 
post-dose at the Day 1 and Week 2 Visits (ages 2 to <4 years), and within 30 minutes pre-dose, and at 1, 2, 4, 6 
and 8 hours post-dose at the Day 1 and Week 2 Visits (ages 7 to <18 years).  
q) 12-lead ECG recorded after subject has rested quietly in a supine position for at least 5 minutes.  
r) Only for subjects participating in the Dose-tapering Period.  
s) Study medication brought by subjects to the Week 2 Visit for dosing and compliance assessment will be 
redispensed to subjects at the end of the visit.  
t) During the Treatment Period, the dose of study medication on the days of the Day 1, Week 2, Week 6, and 
Week 12 Visits will be administered with breakfast in the study clinic. All other doses will be taken with breakfast 
at home.  
u) Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to ensure that the study drug 
tapering is proceeding according to protocol, to assess potential signs or symptoms indicative of adrenal 
suppression, and to address any questions the parent(s)/guardian(s) may have.  
v) Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale will be completed for 
subjects in the 2 to <4 years age group only.  
w) Performance of Upper Limb (PUL) test will be performed by subjects in the 7 to <18 years age group only.  
x) Ease of Study Medication Administration Assessment will be completed for subjects in the 2 to <4 years age 
group only.  
y) Study Medication Acceptability Assessment will be completed by subjects in the 7 to <18 years age group 
only.  
z) Subject diaries used to record any changes in concomitant medications taken, any AEs experienced during the 
study, and any incomplete or missed doses of study medication.  
aa) All AEs and SAEs must be recorded in the source documents and eCRF from the date of the subject’s written 
informed consent until the final Week 16 Visit or the subject’s participation in the study is completed (SAEs 
through 30 days after final dose study drug). Ongoing AEs will be followed to resolution, stabilization, or until 
such time the Investigator believes follow-up is not necessary.  
bb) For subjects who do not continue into an expanded access or compassionate use program, site staff will make a 
phone call to the home 31-35 days after the final dose of study medication in VBP15 006 Dose-tapering Period to 
confirm the final SAE status of the subject. 

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cc) Subjects who elect to continue vamorolone therapy by enrolling directly into an expanded access or 
compassionate use program or who will transition directly to SoC glucocorticoid therapy may be discharged from 
the study following completion of all final Week 12 assessments. 
dd) Subjects who participate in the Dose-tapering Period may be discharged from the study following completion 
of all final Dose-tapering Visit assessments (Week 16). 
ee) Including Ambulatory Status 
 
6.3 Visit Schedule and Procedures 
Original Text 
 (…) 
Each subject will receive the assigned, open-label study medication at stable daily dose 
for a period of 12 weeks.  Following completion of the 12-week Treatment Period, all 
subjects who will not be continuing directly to receive vamorolone by expanded access 
or compassionate use or transitioning directly to SoC glucocorticoid therapy will taper 
their study medication during the 4-week Dose-tapering Period and will return to the 
study site for study assessments at the end of the Dose-tapering Period (Week 16) ‘’See 
Section 7 for a detailed description of the safety, PK, clinical efficacy, PD, behavior 
and neuropsychology, physical functioning, and sleep-wake activity assessments to be 
performed during this study. 
Revised Text 
 (…) 
Each subject will receive the assigned, open-label study medication at stable daily dose 
for a period of 12 weeks.  Following completion of the 12-week Treatment Period, all 
subjects who will not be continuing directly to receive vamorolone by expanded access 
or compassionate use or transitioning directly to SoC glucocorticoid therapy will taper 
their study medication during the Dose-tapering Period (up to 8 weeks) and will return 
to the study site for study assessments at the end of the Dose-tapering Period, ’See 
Section 7 for a detailed description of the safety, PK, clinical efficacy, PD, behavior 
and neuropsychology, physical functioning, and sleep-wake activity assessments to be 
performed during this study. 
 
6.3.2 Baseline Period (Day -1) Visit 
Original Text 
 (…) 
The following procedures will be completed at the Baseline Day -1 Visit: 
x Physical examination including weight (in kilograms) and assessment of 
cushingoid features (see Section 7.2.2)  
(…) 

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Revised Text 
 (…) 
The following procedures will be completed at the Baseline Day -1 Visit: 
x Physical examination including weight (in kilograms) and assessment of 
cushingoid features and ambulatory status (see Section 7.2.2)  
(…) 
 
 
6.3.3 Treatment Period Day 1 Visit 
Original Text 
 (…) 
x Blood samples for PD biomarkers including fasting glucose and insulin, 
osteocalcin, CTX, serum P1NP, and morning cortisol, prior to administration of 
first dose of study drug (see Section 7.2.6).  Blood remaining from collected 
samples not needed for protocol-specified analyses may be stored for future 
exploratory biomarker studies. 
(…) 
Revised Text 
 (…) 
x Blood samples for PD biomarkers including fasting glucose and insulin, 
osteocalcin, CTX, serum P1NP, and morning cortisol, prior to administration of 
first dose of study drug (see Section 7.2.6).  Blood remaining from collected 
samples not needed for protocol-specified analyses may be stored for future 
exploratory biomarker studies, including in the additional 12 to <18 years age 
group: suppression of the gonadal axis (LH, FSH) and suppression of the 
thyroid axis (TSH, FT4). 
(…) 
 
6.3.5 Dose-tapering Period (Weeks 13-16) 

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Original Text 
All subjects who complete the study and opt not to continue directly with vamorolone 
treatment in an expanded access or compassionate use program, and who will not 
transition directly to SoC glucocorticoid treatment for DMD, will participate in a 4-
week doubleblind Dosetapering Period during which the dose of study medication will 
be progressively reduced and discontinued prior to discharge from the study.  In 
addition, subjects who discontinue study medication after the first dose and prior to 
Week 12 will also participate in the Dose-tapering Period if possible and if, in the 
opinion of the Investigator, it is safe to do so.   
The purpose of dose-tapering is to aid in re-establishment of adrenal function if adrenal 
suppression has occurred during vamorolone treatment.  Dose tapering will be 
performed in a stepwise manner, according to the subject’s most recent calculated 
liquid formulation dose during the 12-week Treatment Period.  
Dose tapering for vamorolone will be performed as outlined in Table 8.  For subjects 
who have completed the Treatment Period, the subject’s weight recorded at the 
Week 12 Visit will be used to calculate dose volume for all dose de-escalations during 
the Dose-tapering Period. 
Table 8. 
Study Medication Dose Tapering 
Treatment Period 
Dose Level 
Week 13 
Dose Level 
Week 14 
Dose Level 
Week 15 
Dose Level 
Week 16 
Dose Level 
Formulation: 100% 
50% 
25% 
10% 
0% 
 
Subjects will take the first dose of study medication in the Dose-tapering Period 
(Week 13 dose level) with a meal on the day following the Week 12 dose of study 
medication.in the glucocorticoid-treated cohorts, mainly those who have been on GC 
treatment for many months or yearon  
Site study staff will contact the parent(s)/guardian(s) by telephone at Week 14 to 
ensure that the dose tapering is proceeding according to protocol, to assess potential 
signs or symptoms indicative of adrenal suppression, and to address any questions the 

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parent(s)/guardian(s) may have.  In addition, subjects will be assessed promptly for 
adrenal suppression if unwell at any time during the Dose-Tapering Period.  There will 
be a low threshold for recommending commencement of daily oral prednisone or 
hydrocortisone, or intravenous hydrocortisone if hospitalization occurs in these 
circumstances. 
The final end-of-study visit will be scheduled approximately one week after the final 
dose de-escalation to 0 mg/kg.  Each subject will return to the study site for final study 
assessments when he has received no study medication for one week (Study Week 16).   
Subjects will have non-fastingblood and urine samples collected for clinical laboratory 
tests at the final Week 16 Visit.  Subjects will also have a physical examination with 
weight, assessment of cushingoid features and vital signs recorded.  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.   
Subjects participating in the Dose-tapering Period will be discharged from the study 
following completion of all Dose-tapering Period assessments. 
 
Revised Text 
All subjects who complete the study and opt not to continue directly with vamorolone 
treatment in an expanded access or compassionate use program, and who will not 
transition directly to SoC glucocorticoid treatment for DMD, will participate in a Dose 
tapering Period during which the dose of study medication will be progressively 
reduced.  In addition, subjects who discontinue study medication after the first dose 
and prior to Week 12 will also participate in the Dose-tapering Period if possible and if, 
in the opinion of the Investigator, it is safe to do so.   
The purpose of dose-tapering is to aid in re-establishment of adrenal function if adrenal 
suppression has occurred during vamorolone treatment.  Dose tapering will be 

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recommending commencement of daily oral prednisone or hydrocortisone, or 
intravenous hydrocortisone if hospitalization occurs in these circumstances. 
The end-of-study visit (Week 16) will be scheduled approximately one week after the 
final de-escalation to 0 mg but 1 to 3 days after the last dose of vamorolone, i.e. after 
starting hydrocortisone, in the steroid-treated 7 to <18 years age group on 6 mg/kg/day 
at Week 12.  
Subjects will have non-fasting but morning blood and urine samples collected for 
clinical laboratory tests at the Week 16 Visit.  Subjects will also have a physical 
examination with weight, assessment of cushingoid features and vital signs recorded.  
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.   
Subjects participating in the Dose-tapering Period will be discharged from the study 
following completion of all Dose-tapering Period assessments. 
 
 
7.1 Demographic Assessments 
Original Text 
Demographic information (age at enrollment, race, and ethnicity) will be collected 
during the Pretreatment Screening Period and will be recorded on the appropriate 
eCRF page. 
Revised Text 
Demographic information (age at enrollment, race and ethnicity, and date of birth may 
also be collected where allowed) will be collected during the Pretreatment Screening 
Period and will be recorded on the appropriate eCRF page. 
 
7.2.2. Physical Examination, Cushingoid Features, Ambulatory status, Weight, and 
Height 
Original text 
7.2.2 Physical Examination, Cushingoid Features, Weight, and Height 

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A complete physical examination will be performed at Screening, Baseline Day -1, 
Week 6, and Week 12, and at the final Week 16 Dose-tapering Period Visit, 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.  Particular attention will be paid to any sign or symptom of infection. Clinically 
significant changes from baseline should be recorded as AEs.  Particular attention will 
be paid in identifying any sign of cushingoid features, which should also be recorded 
as AEs if they first appear or worsen during the study.  
Additional unscheduled symptom-directed physical examinations may be conducted at 
any time at the Investigator’s discretion.   
Height (in cm) will be recorded at Screening and Week 12.  Standing height will be 
recorded for subjects in the 2 to <4 years age group and all participants in the 7 to <18 
years age group who can stand independently.  Ulnar length of the non-dominant arm, 
measured from the olecranon (point of elbow) to the styloid process (prominent bone 
of the wrist), will be used to calculate height for subjects in the 7 to <18 years age 
group (see Manual of Operations for a detailed description of methodology). 
Weight (in kg) will be recorded at Screening, Baseline, Day -1, Week 2, Week 6, and 
Week 12, and at the final Week 16 Dose-tapering Visit. Weight recorded at the 
dispensing visit will be used to calculate the study medication dose for the subsequent 
dispensing interval (see Section 5.3).   
Results will be recorded in the source document and on the appropriate eCRF page. 
  
Revised text 
7.2.2 Physical Examination, Cushingoid Features, Ambulatory status, Weight, and 
Height 
A complete physical examination will be performed at Screening, Baseline Day -1, 
Week 6, and Week 12, and at the final Dose-tapering Period Visit, 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.  Particular 
attention will be paid to any sign or symptom of infection. Clinically significant 
changes from baseline should be recorded as AEs.  Particular attention will be paid in 
identifying any sign of cushingoid features, which should also be recorded as AEs if 
they first appear or worsen during the study. Ambulatory status as assessed by the 
investigator will be recorded at Baseline. 

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Additional unscheduled symptom-directed physical examinations may be conducted at 
any time at the Investigator’s discretion.   
Height (in cm) will be recorded at Screening and Week 12.  Standing height will be 
recorded for subjects in the 2 to <4 years age group and all participants in the 7 to <18 
years age group who can stand independently.   
Weight (in kg) will be recorded at Screening, Baseline, Day -1, Week 2, Week 6, and 
Week 12, and at the final Week 16 Dose-tapering Visit. Weight recorded at the 
dispensing visit will be used to calculate the study medication dose for the subsequent 
dispensing interval (see Section 5.3).   
Results will be recorded in the source document and on the appropriate eCRF page. 
 
 
7.2.6 Pharmacodynamic Biomarker Panel 
Original text 
Blood samples will be collected to explore the effect of vamorolone on biomarkers 
associated with glucocorticoid safety concerns (exploratory outcomes for adrenal 
suppression, insulin resistance, and bone turnover), as listed in Table 11.   
(…) 
Blood remaining from collected samples not needed for protocol-specified analyses at 
each of the blood collection time points may be stored for future exploratory biomarker 
studies for aspects of safety and efficacy.  These remaining blood samples may be 
released to scientists worldwide for research purposes, including research on 
biomarkers in DMD.  Any released samples will have no identifying subject 
information.   
Additional blood samples for HbA1c determination should be collected if urine 
glucose is positive and/or fasted glucose levels are above normal limits at any of the 
scheduled assessment time points (see Laboratory Manual).  

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A total of approximately 12 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin, morning cortisol, osteocalcin, CTX, and P1NP) and 
measurement of HbA1c over the course of the 21-week study (see Section 7.2.8).   
Table 11. Pharmacodynamic Biomarkers – Exploratory Safety Outcomes 
Adrenal Suppression 
Cortisol – morning 
Insulin Resistance 
Glucose – fasting 
Insulin – fasting 
HbA1c 
Bone Turnover 
Osteocalcin 
CTX 
P1NP 
 
 
Revised text 
Blood samples will be collected to explore the effect of vamorolone on biomarkers 
associated with glucocorticoid safety concerns (exploratory outcomes for adrenal 
suppression, insulin resistance, and bone turnover, as well as, in the additional 12 to 
<18 years age group, suppression of the gonadal axis (LH, FSH) and suppression of the 
thyroid axis (TSH, FT4)), as listed in Table 6. 
(…) 
Blood remaining from collected samples not needed for protocol-specified analyses at 
each of the blood collection time points may be stored for future exploratory biomarker 
studies for aspects of safety and efficacy.  These remaining blood samples may be 
released for research purposes, including research on biomarkers in DMD.  Any 
released samples will have no identifying subject information.   
Additional blood samples for HbA1c determination should be collected if urine 
glucose is positive and/or fasted glucose levels are above normal limits at any of the 
scheduled assessment time points (see Laboratory Manual).  

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A total of approximately 12 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin, morning cortisol, osteocalcin, CTX, and P1NP, as well as, 
in the additional 12 to <18 years age group, LH, FSH, TSH, FT4)) and measurement of 
HbA1c over the course of the 21-week study (see Section 7.2.8).   
Table 6. 
Pharmacodynamic Biomarkers – Exploratory Safety Outcomes 
Adrenal Suppression 
Cortisol – morning 
Insulin Resistance 
Glucose – fasting 
Insulin – fasting 
HbA1c 
Bone Turnover 
Osteocalcin 
CTX 
P1NP 
Suppression of the gonadal axis 
LH 
FSH 
Suppression of the thyroid axis 
TSH 
FT4 
 
7.6 Adverse Events and Serious Adverse Events 
Original text 
The condition of the subjects, inclusive of lab value, will be monitored throughout the 
duration of the study by the clinical site study team and by recording of AEs in subject 
An AE is any untoward medical occurrence in a subject and 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 drug.  Pre-existing conditions that 
worsen during a study are to be reported as AEs. 
 
Revised text 

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An AE is any untoward medical occurrence in a subject and 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 drug.  Pre-existing conditions that 
worsen during a study are to be reported as AEs. 
. 
 
7.6.4 Follow-Up of Adverse Events 
Original Text 
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 document 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 further follow-up of AEs will be documented in the source document  and will be 
described in the final report only if considered relevant by the Investigator, the Study 
Chair, The Medical Monitor and/or Sponsor and CRF.  
Revised Text 
Adverse events will be followed until they have returned to baseline status, stabilized, 
or the Investigator 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 document 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 further follow-up of AEs 
will be documented in the source document and CRF.  
 
7.6.6 Serious Adverse Events 
Original Text 
(…)   
During the SAE collection period, the Investigator or clinical site personnel should 
notify the Coordinating Center of all SAEs, regardless of relationship to the 
investigational drug, within 24 hours of clinical staff becoming aware of the event; 
notification to the Coordinating Center will trigger alerts to the Study Chair, the 

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Sponsor, and the Medical Monitor.  The Investigator will provide the initial 
notification by completing the SAE Report Form in the electronic data capture (EDC) 
system, which must include the Investigator’s assessment of the relationship of the 
event to investigational drug, and must be signed by the Investigator. 
In addition, notification is sent by the Investigator to the IRB/IEC and the subject’s 
Primary Care Physician. 
Follow-up information, or new information regarding an ongoing SAE, must be 
provided promptly to the Coordinating Center within 24 hours of knowledge of the 
new or follow-up information, which will forward the information to the Study Chair, 
the Sponsor, and the Medical Monitor. 
(…)   
Any AE (including treatment-emergent, clinically significant, abnormal laboratory test 
values), 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 Coordinating Center, 
who will notify the 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 
Coordinating Center, who will notify the Study Chair, the Sponsor and the Medical 
Monitor, within 24 hours of the Investigator becoming aware of the new information. 
All 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.  All SAEs, related 
and unrelated, must be reported to the Sponsor within 24 hours of first awareness. 
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 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:  
In United States and Canada: 
 
Email: CHOSafety@prahs.com 
 
Drug Safety Fax: 1 888 772 6919 or 1 434 951 3482 
 
SAE Questions: Drug Safety Helpline: 1 800 772 2215  

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In Europe, Asia, Pacific, Africa and Australia: 
 
Email: MHGSafety@prahs.com 
 
Drug Safety Fax: +44 1792 525720 
 
SAE Questions: Drug Safety Helpline: +49 621 878 2154 
 
Revised Text 
(…)   
During the SAE collection period, the Investigator or clinical site personnel should 
notify the Coordinating Center of all SAEs, regardless of relationship to the 
investigational drug, within 24 hours of clinical staff becoming aware of the event; 
notification to the Coordinating Center will trigger alerts to the Sponsor. The 
Investigator will provide the initial notification by completing the SAE Report Form in 
the electronic data capture (EDC) system, which must include the Investigator’s 
assessment of the relationship of the event to investigational drug, and must be signed 
by the Investigator. 
In addition, notification is sent by the Investigator to the IRB/IEC and the subject’s 
Primary Care Physician. 
Follow-up information, or new information regarding an ongoing SAE, must be 
provided promptly to the Coordinating Center within 24 hours of knowledge of the 
new or follow-up information, which will forward the information to , the Sponsor. 
(…)   
Any AE (including treatment-emergent, clinically significant, abnormal laboratory test 
values), 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 Sponsor 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 
Coordinating Center, who will notify the Sponsor within 24 hours of the Investigator 
becoming aware of the new information. 
All 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.  All SAEs, related 
and unrelated, must be reported to the Sponsor within 24 hours of first awareness. 
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 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 

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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 
ICON safety management team within 24 hours, using the contact information 
below:  
In United States and Canada: 
 
Email: CHOSafety@iconplc.com 
 
Drug Safety Fax: 1 888 772 6919 or 1 434 951 3482 
 
SAE Questions: Drug Safety Helpline: 1 800 772 2215  
In Europe, Asia, Pacific, Africa and Australia: 
 
Email: MHGSafety@iconplc.com 
 
Drug Safety Fax: +44 1792 525720 
 
SAE Questions: Drug Safety Helpline: +49 621 878 2154 
 
 
8.1 Study Steering Committee  
Revised Text 
This section is deleted 
 
10.1 Sample Size Determination 
Original Text 
(…) 
For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a total of 
approximately 20 subjects in the 2 to <4 years age group will be enrolled with 
approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day).  A 
total of approximately 24 subjects in the 7 to <18 years age group will be enrolled with 
approximately 12 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day) and 
each dose level group stratified 1:1 by glucocorticoid treatment status at study entry to 
include approximately 6 glucocorticoid-untreated subjects and 6 glucocorticoid-treated 
subjects at study entry. This sample size is considered sufficient to detect drug safety 
concerns in a pediatric population ages 2 to <4 and 7 to <18 years with DMD based on 

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clinical judgment and prior study of vamorolone at these doses. In addition, this sample 
size is sufficiently large to determine PK parameters.   
 
Revised Text 
 (…)   
For this Phase II study in DMD boys ages 2 to <4 years and 7 to <18 years, a total of 
approximately 20 subjects in the 2 to <4 years age group will be enrolled with 
approximately 10 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day).  A 
total of approximately 34 subjects in the 7 to <18 years age group will be enrolled with 
approximately 12 subjects per dose level group (2.0 mg/kg/day and 6.0 mg/kg/day) and 
each dose level group stratified 1:1 by glucocorticoid treatment status at study entry to 
include approximately 6 glucocorticoid-untreated subjects and 6 glucocorticoid-treated 
subjects at study entry, plus 10 subjects for the additional 12 to <18 years age group 
[6.0 mg/kg/day - glucocorticoid-treated].  This sample size is considered sufficient to 
detect drug safety concerns in a pediatric population ages 2 to <4 and 7 to <18 years 
with DMD based on clinical judgment and prior study of vamorolone at these doses. 
The 10 additional 12 to <18 years subjects will further ensure that the full age range is 
included. In addition, this sample size is sufficiently large to determine PK parameters.   
 
 
10.7.5 Pharmacodynamic analyses 
Original Text 
(…) 
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover, as well as exploratory biomarkers of safety and efficacy will be assessed.  
Standard descriptive statistics will be used to summarize PD biomarkers by dose level 
within age group. Change from baseline will be presented.  For subjects 7 to <18 years 
of age, descriptive statistics will be presented separately for those subjects who were 
on SoC glucocorticoid therapy at the time of assignment to a dose group and those 
subjects who had been off SoC glucocorticoid therapy for at least 3 months at the time 
of assignment.  
The changes in serum PD biomarkers will be compared to the data collected in a 
previously conducted vamorolone study VBP15-004. The changes from baseline to 
week 12 in the present study (by dose level and age group) will be compared to the 

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changes from baseline to week 12 in the four treatment groups of study VBP15-004 
(vamorolone 2.0 mg/kg, vamorolone 6.0 mg/kg, placebo and prednisone 0.75 mg/kg). 
Furthermore, the differences between the groups will be evaluated with ANCOVA 
models including baseline value as a covariate and the treatment/age group as a fixed 
factor. Additional analyses will be conducted by glucocorticoid use group, when 
appropriate.   
Revised Text 
 (…)   
Serum PD biomarkers of adrenal axis suppression, insulin resistance, and bone 
turnover, as well as exploratory biomarkers of safety and efficacy (including in the 
additional 12 to <18 years age group: suppression of the gonadal axis (LH, FSH) and 
suppression of the thyroid axis (TSH, FT4)) will be assessed.  Standard descriptive 
statistics will be used to summarize PD biomarkers by dose level within age group. 
Change from baseline will be presented.  For subjects 7 to <18 years of age, descriptive 
statistics will be presented separately for those subjects who were on SoC 
glucocorticoid therapy at the time of assignment to a dose group and those subjects 
who had been off SoC glucocorticoid therapy for at least 3 months at the time of 
assignment.  
The changes in serum PD biomarkers will be compared to the corresponding data if 
available collected in a previously conducted vamorolone study VBP15-004. The 
changes from baseline to week 12 in the present study (by dose level and age group) 
will be compared to the changes from baseline to week 12 in the four treatment groups 
of study VBP15-004 (vamorolone 2.0 mg/kg, vamorolone 6.0 mg/kg, placebo and 
prednisone 0.75 mg/kg). Furthermore, the differences between the groups will be 
evaluated with ANCOVA models including baseline value as a covariate and the 
treatment/age group as a fixed factor. Additional analyses will be conducted by 
glucocorticoid use group, when appropriate.   
 
 

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12.1  Confidentiality 
Original Text 
(…) 
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 redacted 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 information made available for inspection will be handled in the strictest 
confidence and in accordance with all applicable data protection / privacy laws in the 
relevant countries. 
Revised Text 
(…) 
Subject names will remain confidential and will not be included in the database.  Only 
enrollment number, age at enrolment and birth date (may be collected where allowed 
by local regulations) 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 
redacted 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 
information made available for inspection will be handled in the strictest confidence 
and in accordance with all applicable data protection / privacy laws in the relevant 
countries. 
 

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McMillan HJ.  Intermittent glucocorticoid regimes for younger boys with duchenne 
muscular dystrophy: Balancing efficacy with side effects. Muscle Nerve. 2019 Jun; 
59(6): 638-9 
Merlini L, Gennari M, Malaspina E, et al. Early corticosteroid treatment in 4 Duchenne 
muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012; 45(6): 796-802.  
Morgan SA, McCabe EL, Gathercole LL, et al. 11β-HSD1 is the major regulator of the 
tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci USA. 
2014; 111(24): E2482-91. 
Pahl HL. Activators and target genes of Rel/NF-kappa B transcription factors. 
Oncogene. 1999; 18(49): 6853-66. 
Pane M, Mazzone ES, Sivo S, et al. Long term natural history data in ambulant Boys 
with Duchenne muscular dystrophy: 36-month changes. PlosOne. 2014; 10: 
1371/journal.pone.0108205. 
Rodriguez-Gonzalez M, Lubian-Gutierrez M, Cascales-Poyatos HM, et al. Role of the 
Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy. Int J 
Mol Sci. 2020; 22(1): 356. 
Schakman O, Kalista S, Barbé C, et al. Glucocorticoid-induced skeletal muscle 
atrophy. Int J Biochem Cell Biol. 2013; 45(10): 2163-72. 
Webster.JM, Sagmeister MS, Fenton CG, et al. Global Deletion of 11β-HSD1 prevents 
muscle wasting associated with glucocorticoid therapy in polyarthritis. Int J Mol Sci. 
2021; 22(15): 7828-40. 
 
15.4. 
Protocol Amendment #3 Complete List of Changes 
A Protocol version tracking changes between Edition A3 version 1.0 and A2 version 1.0 
will be provided. 
7.2.4 Clinical Laboratory Tests 
Original Text:  
For the hematology, chemistry, and lipids laboratory tests, blood will be collected by 
direct venipuncture of peripheral veins.  A total of approximately 19 mL of blood will 
be collected over the course of this study for clinical safety laboratory evaluation, 
including measurement of vitamin D (see Section 7.2.8 for details of blood volumes to 
be collected).   
Revised Text: 
For the hematology, chemistry, and lipids laboratory tests, blood will be collected by 
direct venipuncture of peripheral veins.  A total of approximately 21 mL of blood will 
be collected over the course of this study for clinical safety laboratory evaluation, 

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including measurement of vitamin D (see Section 7.2.8 for details of blood volumes to 
be collected). 
 
7.2.6 Pharmacodynamic Biomarker Panels 
Original Text:  
Blood samples will be collected pre-dose at the Day 1 and Week 12 Visits for analysis 
of biomarkers for exploratory outcome measures of adrenal suppression, bone 
turnover, and insulin resistance (blood for HbA1c will be collected at Screening and 
Week 12).  Approximately 5 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin [insulin resistance], morning cortisol [adrenal suppression], 
and osteocalcin, P1NP, and CTX [bone turnover] biomarkers) at each scheduled 
collection time point; an additional 1 mL of blood will be collected for 
measurement of HbA1c at each of the scheduled collection time points.  Samples 
collected at the Day 1 and Week 12 Visits will be collected after the subject has fasted 
for ≥ 6 hours and prior to administration of the daily dose of study medication; the 
sample collected at the Screening Visit for HbA1c measurement may be collected non-
fasting.  Blood for morning cortisol measurement should be collected before 10 AM 
local time. 
[…] 
Additional blood samples for HbA1c determination should be collected if urine 
glucose is positive and/or fasted glucose levels are above normal limits at any of the 
scheduled assessment time points (see Laboratory Manual).  
A total of approximately 12 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin, morning cortisol, osteocalcin, CTX, and P1NP, as well as, 
in the additional 12 to <18 years age group, LH, FSH, TSH, FT4) and measurement 
of HbA1c over the course of the 21-week study (see Section 7.2.8). 
Revised Text: 
Blood samples will be collected pre-dose at the Day 1 and Week 12 Visits for analysis 
of biomarkers for exploratory outcome measures of adrenal suppression, bone 
turnover, and insulin resistance (HbA1c will be analyzed at Screening and Week 12).  
Approximately 6 mL of blood will be collected for the PD biomarker panel (fasting 
glucose and insulin [insulin resistance], morning cortisol [adrenal suppression], and 
osteocalcin, P1NP, and CTX [bone turnover] biomarkers) at each scheduled collection 
time point; HbA1c will be analyzed from the hematology sample .  Samples 
collected at the Day 1 and Week 12 Visits will be collected after the subject has fasted 
for ≥ 6 hours and prior to administration of the daily dose of study medication; the 
sample collected at the Screening Visit for HbA1c measurement may be collected non-
fasting.  Blood for morning cortisol measurement should be collected before 10 AM 
local time. 
[…] 

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Amendment #3                            
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IND 118, 942 
 
Page 230 of 232 
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Additional HbA1c determination should be performed if urine glucose is positive 
and/or fasted glucose levels are above normal limits at any of the scheduled assessment 
time points (see Laboratory Manual).  
A total of approximately 19 mL of blood will be collected for the PD biomarker panel 
(fasting glucose and insulin, morning cortisol, osteocalcin, CTX, and P1NP, as well as, 
in the additional 12 to <18 years age group, LH, FSH, TSH, FT4) over the course of 
the 21-week study (see Section 7.2.8). 
 
7.2.7 Pharmacokinetic Assessment 
Original Text:  
At the Day 1 and Week 2 Visits, all subjects will have blood collected for PK 
assessments within 30 minutes prior to and at 1, 2, and 6 hours (ages 2 to <4 years), or 
within 30 minutes prior to and at 1, 2, 4, 6 and 8 hours (ages 7 to <18 years) following 
administration of the daily dose of study medication.  Approximately 2 mL of blood 
will be collected into K2-EDTA tubes at each assessment time point (total of 16 mL 
blood collected for PK assessment in 2 to < 4-year-old subjects and total of 24 mL 
blood collected for PK assessments in ages 7 to <18 years). 
Revised Text: 
At the Day 1 and Week 2 Visits, all subjects will have blood collected for PK 
assessments within 30 minutes prior to and at 1, 2, and 6 hours (ages 2 to <4 years), or 
within 30 minutes prior to and at 1, 2, 4, 6 and 8 hours (ages 7 to <18 years) following 
administration of the daily dose of study medication.  Approximately 1.2 mL of blood 
will be collected into K2-EDTA tubes at each assessment time point (total of 
approximately 10 mL blood collected for PK assessment in 2 to < 4-year-old subjects 
and total of approximately 15 mL blood collected for PK assessments in ages 7 to <18 
years). 
 
7.2.8 Total Blood Volume Required 
Original Text:  
The number and volume of blood samples and total volume of blood to be collected from 
each subject throughout the duration of the up-to-21-week study are summarized in 
Table 7.  A total of 48.3 mL of blood will be collected from each 2 to <4-year-old subject, 
and 52.3 mL of blood will be collected from each 7 to <18-year-old subject over the 
course of the up-to-21-week study. 
Table 7. 
Blood Sample Number and Volume by Study Visit 
 
Blood Volume (mL) 
Test 
SCR 
Day 1 
Week 2 
Week 6 
Week 12 
Week 16 
Total 
Volume 
Clinical Safety Labsa 
3.5b 
3.5b 
 
3.5b 
3.5b 
3.5b 
17.5 

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Varicella Zoster IgG 
2 
 
 
 
 
 
2 
Vitamin D 
1.2 
 
 
 
1.2b 
 
2.4 
PD Biomarker Panelc 
 
8.2b 
 
 
8.2b 
 
16.4 
HbA1c 
1 
 
 
 
1b 
 
2 
PKd 
Ages 2 to <4 years 
Ages 7 to <18 years 
 
 
4 
6 
 
4 
6 
 
 
 
 
8 
12 
Total Volume by Visit (mL) 
Ages 2 to <4 years 
Ages 7 to <18 years 
7.7 
 
15.7 
17.7 
 
4 
6 
3.5 
13.9 
3.5 
 
48.3 
52.3 
Total Volume: 48.3 mL (ages 2 to <4 year); 52.3 mL (ages 7 to <18 year) 
SCR = Screening 
a Hematology, Chemistry, Lipids 
b Subjects must have fasted ≥ 6 hours prior to blood draws. 
c Fasting glucose, insulin, morning cortisol, CTX, P1NP, osteocalcin; pre-dose on Day 1 and Week 12.   
d Blood drawn for population PK within 30 minutes pre-dose and at 1, 2, and 6 hours post-dose at the Day 1 
and Week 2 Visits (ages 2 to <4 years), or 30 minutes pre-dose and at 1, 2, 4, 6 and 8 hours post-dose at the 
Day 1 and Week 2 Visits (ages 7 to <18 years).  Subjects must be fasting at the time of collection of the 
Day 1 and Week 2 pre-dose samples. 
 
 
Revised Text: 
The number and volume of blood samples and total volume of blood to be collected from 
each subject throughout the duration of the up-to-21-week study are summarized in Table 
7.  A total of approximately 51 mL of blood will be collected from each 2 to <4-year-old 
subject, and appoximately 56 mL of blood will be collected from each 7 to <18-year-old 
subject over the course of the up-to-21-week study. 
Table 7. 
Blood Sample Number and Volume by Study Visit 
 
Blood Volume (mL) 
Test 
SCR 
Day 1 
Week 2 
Week 6 
Week 12 
Week 16 
Total 
Volume 
Clinical Safety Labsa 
3.7b 
3.7b 
 
3.7b 
3.7b 
3.7b 
18.5 
Varicella Zoster IgG 
2 
 
 
 
 
 
2 
Vitamin D 
1.2 
 
 
 
1.2b 
 
2.4 
PD Biomarker Panelc 
 
9.2b 
 
 
9.2b 
 
18.4 
PKd 
Ages 2 to <4 years 
Ages 7 to <18 years 
 
 
4.8 
7.2 
 
4.8 
7.2 
 
 
 
 
9.6 
14.4 

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Amendment #3                            
Document No. VBP15-006-A3 (Version 1.0) 
Protocol No.: VBP15-006 
 
IND 118, 942 
 
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Total Volume by Visit (mL) 
Ages 2 to <4 years 
Ages 7 to <18 years 
6.9 
 
17.7 
20.1 
 
4.8 
7.2 
3.7 
14.1 
3.7 
 
50.9 
55.7 
Total Volume: 50.9 mL (ages 2 to <4 year); 55.7 mL (ages 7 to <18 year) 
SCR = Screening 
a Hematology, Chemistry, Lipids, HbA1c 
b Subjects must have fasted ≥ 6 hours prior to blood draws. 
c Fasting glucose, insulin, morning cortisol, CTX, P1NP, osteocalcin; pre-dose on Day 1 and Week 12.   
d Blood drawn for population PK within 30 minutes pre-dose and at 1, 2, and 6 hours post-dose at the Day 1 
and Week 2 Visits (ages 2 to <4 years), or 30 minutes pre-dose and at 1, 2, 4, 6 and 8 hours post-dose at the 
Day 1 and Week 2 Visits (ages 7 to <18 years).  Subjects must be fasting at the time of collection of the 
Day 1 and Week 2 pre-dose samples.