A Multicenter Open-Label Study on the Safety and Efficacy of Deflazacort (Emflaza) in Subjects With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
Phase: PHASE3
Conditions: Limb-Girdle Muscular Dystrophy
Sponsor: PTC Therapeutics

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CLINICAL PROTOCOL 
A MULTICENTER OPEN LABEL STUDY ON THE SAFETY AND EFFICACY OF 
DEFLAZACORT (EMFLAZA®) IN SUBJECTS WITH LIMB-GIRDLE MUSCULAR 
DYSTROPHY 2I (LGMD2I) 
PTCEMF-GD-004 
25 MARCH 2020 
VERSION 4.0 
PTC THERAPEUTICS, INC. 
100 CORPORATE COURT 
SOUTH PLAINFIELD, NJ 07080 USA 
NCT #NCT03783923

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Notice of Proprietary Information: This document contains confidential information owned by or in the 
possession/control of PTC Therapeutics, Inc. Except as may otherwise be permitted in writing, by accepting or 
reviewing these materials, you agree that this information should not be disclosed to others (except where 
required by applicable law) and should not be used for unauthorized purposes. In the event of an actual or 
suspected breach of this obligation, PTC Therapeutics, Inc. should be notified promptly.

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SYNOPSIS 
Study Number: 
PTCEMF-GD-004 
Name of Investigation 
Product: 
Deflazacort (Emflaza) 
Study Title: 
A Multicenter Open Label Study on the Safety and Efficacy of Deflazacort 
(Emflaza®) in Subjects with Limb-Girdle Muscular Dystrophy 2I (LGMD2I) 
Proposed Indication 
Limb-Girdle Muscular Dystrophy Type 2I 
Number of Study 
Sites: 
Approximately 5 
Phase of Trial: 
N/A 
Study Objectives: 
Primary Study Objective 
• 
To evaluate the efficacy of deflazacort as measured by muscle 
function in subjects with Limb-Girdle Muscular Dystrophy Type 2I 
(LGMD2I) 
Secondary Study Objectives 
• 
To evaluate the effects of deflazacort on pulmonary function in 
subjects with LGMD2I  
• 
To evaluate the pharmacokinetic (PK) profile of deflazacort in 
subjects with LGMD2I 
• 
To evaluate safety of deflazacort in subjects with LGMD2I 
Exploratory Objective 
• 
To evaluate the predictive value of global T2 MRI as a measure of 
efficacy of deflazacort in subjects with LGMD2I 
• 
To evaluate quality of life by the Individualized Neuromuscular 
Quality of Life (INQoL) questionnaire in subjects with LGMD2I 
Study Endpoints 
Primary Efficacy Endpoint(s) and Evaluation(s) 
• 
Change from baseline in time to climb 4 stairs after 26 weeks of 
treatment 
Secondary Endpoints and Evaluation(s) 
• 
Secondary efficacy endpoints 
o Change from baseline in forced vital capacity (FVC) after 26 
weeks of treatment 
o Change from baseline in 2-minute walk test after 26 weeks of 
treatment 
o Change from baseline in time to up and go after 26 weeks of 
treatment 
o Change from baseline to time to descend 4 stairs after 26 weeks 
of treatment 
o Change from baseline in time to run/walk 10 meters after 26 
weeks of treatment 
o Change from baseline in maximal inspiratory pressure (MIP) 
and maximal expiratory pressure (MEP) after 26 weeks of 
treatment 
o Change from baseline in hand-held myometry after 26 weeks of 
treatment 

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o Change from baseline in global T2 relaxation time of selected 
upper and lower limb muscles after 26 weeks of treatment 
• 
Safety profile characterized by type, frequency, severity, timing, and 
relationship to study drug of any adverse events, laboratory 
abnormalities, electrocardiogram (ECG) abnormalities, 
ophthalmologic abnormalities, dual-energy X-ray absorptiometry 
(DEXA) to evaluate bone density and/or X-ray to assess spine 
fracture 
• 
Pharmacokinetic assessments at baseline and after 13 weeks of 
treatment 
Exploratory Endpoints 
• 
Change from baseline in muscular fat fraction using Dixon magnetic 
resonance imaging of selected lower limb muscles after 26 weeks of 
treatment 
• 
Change from baseline in the INQoL questionnaire in subjects with 
LGMD2I after 26 weeks of treatment 
Study Population: 
Subjects with LGMD2I; age ≥18 years 
Sample Size 
Approximately 30 subjects will receive deflazacort 
Methodology/Study 
Design 
26-week open-label period in which all subjects will receive deflazacort.  
Main Inclusion 
Criteria  
1. 
Genetic diagnosis of LGMD2I (confirmed mutation in the FKRP 
gene) 
2. 
Male and female subjects aged ≥18 years 
3. 
Ability to ascend 4 stairs ≥2.5 seconds and be able to complete the 
ascent and descent at screening and baseline 
4. 
Ability to understand the nature of the study and the consent form 
and to comply with study related procedures 
5. 
Must weigh ≥35 to ≤112.5 kg 
Main Exclusion 
Criteria 
1. 
Received ≥4 weeks of continuous, systemic corticosteroid therapy 
within 3 months of the study Screening Visit 
2. 
Presence of significant cardiomyopathy as defined by 
echocardiogram (left ventricular ejection fraction <30%) at 
screening  
3. 
Requires fulltime ventilator support 
4. 
History of chronic systemic fungal or viral infections 
5. 
History of recent bacterial infection (including tuberculosis) per 
discretion of the Investigator  
6. 
Diagnosis of diabetes mellitus (controlled and/or uncontrolled) 
defined as HbA1c ≥6.5% (based on historical or present diagnosis) 
7. 
History of immunosuppression or other contraindications to 
glucocorticosteroid therapy 
8. 
Requires concomitant use or >1 week of drugs or substances that 
are moderate to strong CYP3A4 inhibitors (ie, clarithromycin, 
fluconazole, diltiazem, verapamil, grapefruit juice) or moderate or 
strong CYP3A4 inducers (ie, rifampin, efavirenz, carbamazepine, 
phenytoin) at baseline 

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9. 
Participated in an interventional clinical trial within the last 3 
months prior to the baseline visit  
10. Unable or unwilling to comply with the contraceptive requirements 
of the protocol 
11. Female subjects who are pregnant and/or breastfeeding 
12. Evidence or history of clinically significant hematological, renal, 
endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, 
neurologic, psychiatric, or allergic disease 
Study Treatment: 
• 
Oral deflazacort (target dose 0.6 mg/kg/day), may be reduced in 
case of tolerability issues  
Duration of 
Treatment: 
26-week open-label 
Safety Monitoring 
Subjects will be monitored closely for adverse events or laboratory 
abnormalities, or other safety assessments (ie, height, weight, vital signs, 
electrocardiograms, and physical examination) during the course of the 
study. 
For adverse events (AEs) or laboratory abnormalities, the Investigator 
should use his/her judgment in determining whether the event or 
abnormality is clinically significant, whether diagnostic evaluation is 
warranted, and whether potential interruption of study drug therapy is 
appropriate. 
While specific monitoring, diagnostic testing, and supportive care 
measures must be instituted based on the clinical judgment of the 
Investigator, investigators are encouraged to contact the medical 
monitor to obtain guidance and to ascertain whether similar events are 
being seen at other sites. The medical monitor should be notified of any 
adverse event or laboratory abnormality that leads to dose interruption 
and should be apprised of ancillary laboratory or other diagnostic 
findings and the evolving data from any work-up of the initial 
abnormality. The medical monitor may suggest review of the case with 
gastroenterology, endocrinology, nephrology consultants or with other 
experts (either at the site or retained by PTC Therapeutics). 
Serious Adverse Event 
Reporting 
All serious adverse events (SAEs) should be reported via the SAE report 
form to PTC Therapeutics within 24 hours of becoming aware of the 
event(s). 
Pharmacokinetic 
Sampling 
Pharmacokinetic sampling will occur at the baseline and Week 13 visits. 
Statistical Methods: 
This is a single arm, open label study to evaluate the efficacy and safety 
of deflazacort in subjects with LGMD2I. The primary endpoint is the 
change in 4-stair climb in seconds after 26 weeks of treatment. Summary 
statistics such as mean, standard deviation, median, minimum and 
maximum will be provided for the change in 4-stair climb in seconds 
after 26 weeks of treatment. The 95% confidence interval for the mean 
will be provided as well. 
If assuming deflazacort can prevent subjects’ further progression within 6 
months i.e. the mean change of 4-stair climb after 26 weeks of treatment 

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is Zero second and the standard deviation of the change is 0.7, with a total 
of 30 subjects, the 95% confidence will be from -0.25 to 0.25 seconds. 
Timing of 
Assessments 
See Schedule of Events  

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Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
A signed and dated informed consent 
must be obtained before conducting any 
study procedures. 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
Medical/Surgical 
History 
X 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
FKRP Genotyping 
X 
 
 
 
 
 
 
 
 
Samples will be collected for sequencing 
of the FKRP gene to confirm the 
presence of a mutation. Genetic testing 
for FKRP will not be performed if 
documentation of genetic diagnosis is 
available at screening. 
Enrollment 
 
X 
 
 
 
 
 
 
 
The site will conduct initial subject 
registration in the IRT system at 
Screening. At Visit 1 (baseline), eligible 
subjects will be assigned dose via the 
IRT system. 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
 
X 
X 
 
X 
X 
 
 
Clinical Labs 
(Hematology6 and 
Chemistry7) 
X 
X 
 
X 
X 
 
X 
X 
 
Fasting approximately 8 hours prior to 
assessments. 
Pregnancy Test8 
X 
X 
 
X 
X 
 
X 
X 
 
All urine pregnancy tests taken at site 
will be confirmed by serum HCG. The 
urine pregnancy test must be negative 
prior to dispensation of study drug. 
Height/Weight/BMI 
X 
X 
 
X 
X 
 
X 
X 
 
For study inclusion, weight range must 
be ≥35 to ≤112.5 kg 
Vitals (HR & BP) 
X 
X 
 
X 
X 
 
X 
X 
 
 
ECG 
X 
 
 
X 
X 
 
 
X 
 
 
Echocardiogram 
X 
 
 
 
 
 
 
 
 
Echocardiograms obtained within 3 
months of enrollment are sufficient to 
obviate the screening echocardiogram. 

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Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
AE/SAE 
monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications information 
will need to be collected starting 30 days 
prior to first dose of study drug. 
Ophthalmic Exam9 
 
X 
 
 
X 
 
 
X 
 
Ophthalmic exams may be scheduled 
within 45 days of scheduled visit to 
accommodate scheduling restrictions. 
Lateral Spine 
X-ray10 
 
X 
 
 
X 
 
 
X 
 
 
DEXA10 
 
X 
 
 
X 
 
 
X 
 
 
Columbia Suicide 
Rating Scale 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Blood 
Sampling11 
 
X 
 
X 
 
 
 
 
 
PK samples will be drawn at Visit 1 and 
Visit 2 (steady state) for pharmacokinetic 
evaluation. The following PK parameters 
if possible, will be calculated using 
noncompartmental analysis method: 
AUC(0-t), AUC(0-inf), Cmax, Tmax, CL/F, 
Vz/F, λz, and t½,. Samples will be drawn 
at pre-dose, and 0.5, 1, 2, 4, and 6 
hours post-dose at baseline and Week 
13 visits. 
 
 
 
 
 
 
 
 
 
 
 
Timed Function 
Tests12 
X 
X 
 
X 
X 
 
X 
X 
 
Timed function tests will be recorded 
and assessed centrally in addition to the 
site’s clinical evaluator’s assessment at 
the visit. Timed function tests include 
time to up and go, time to descend 4 
stairs, time to climb 4 stairs, time to 
run/walk 10 meters, and 2-minute walk 
test. Conduct details will be summarized 
in a manual separate from this protocol. 
Hand Held 
 
X 
 
X 
X 
 
X 
X 
 
 

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Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
Myometry12 
Pulmonary 
Function Testing12 
 
X 
 
 
X 
 
X 
X 
 
Pulmonary function will be evaluated by 
spirometry. Pulmonary function test 
procedures will be detailed in a manual 
separate from this protocol. The 
following pulmonary function tests will be 
evaluated: FVC, MIP, and MEP.  
Biomarker testing 
(Bone Health 
Assays)13 
 
X 
 
X 
X 
 
 
X 
 
 
INQoL 
Questionnaire14 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI12,15 
 
X 
 
X 
X 
 
 
X 
 
Dixon MRI and T2 MRI will evaluate 
muscular fat fraction and inflammation, 
respectively, of selected lower limb 
muscles. Details will be further 
elucidated in an MRI manual separate 
from this protocol. 
Study Drug 
Administration 
 
 
 
 
 
 
 
 
 
 
Dispense Drug 
via IRT 
 
X 
 
X 
X 
 
X 
 
 
 
Unused Drug 
Return/ 
Compliance 
 
 
 
X 
X 
 
X 
X 
X5 
 
Abbreviations: AE, adverse event; BP, blood pressure; BMI, body mass index; DEXA; dual-energy X-ray absorptiometry; ECG, electrocardiogram; ET, early 
termination; FKRP, fukutin-related protein gene; FVC, forced vital capacity; HCG; human chorionic gonadotropin; HR, heart rate; INQoL, Individualized 
Neuromuscular Quality of Life; IRT, Interactive Response Technology; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MRI, magnetic 
resonance imaging; PD, pharmacodynamic; PK, pharmacokinetic; SAE, serious adverse event 
Note: See also Section 3.4 for explanation of the transition from Protocol Version 3.0 to Version 4.0. 
1 
Screening procedures must take place within 42 days of baseline visit (Visit 1). No study-related procedures should be performed prior to the signature of the 
informed consent document(s). 
2 
Any screening procedure completed within and including 7 days of Visit 1, with the exception of the time to climb 4 stairs, can serve as baseline and does not 
need to be repeated at Visit 1. The time to climb 4 stairs must always be performed twice at the baseline visit and all other visits. The second 4 stair climb 

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test should be done a minimum of 5 minutes after the prior test, or any other physical activity. The baseline visit may be split into two consecutive days. 
3 
At Visit 3, subjects initially randomized to deflazacort will continue deflazacort treatment while subjects originally randomized to placebo will initiate 
deflazacort treatment at a target dose of 0.6 mg/kg/day. For placebo subjects, all assessments will be performed prior to first dose of deflazacort (See also 
Section 3.4 for explanation of the transition from Protocol Version 3.0 to Version 4.0).  
4 
At Visit 5/ET, subjects/Investigators who elect to discontinue corticosteroid therapy altogether will need to taper off deflazacort. If it is determined by the 
Investigator that any subject will discontinue the study, all early termination visit procedures should be completed and the final visit should be captured as 
early termination (ET) in an electronic case report form (eCRF). If it is determined that a subject will discontinue the study in between visits, the subject 
should return at earliest convenience for an early termination visit, following completion of any required study medication assessments. For subjects who 
terminated early/ discontinued from the study and are tapering off deflazacort, a follow-up visit will occur approximately 4 weeks after the final study drug 
dose. In case of discontinuation due to an AE, the AE should be followed up by the investigator until it is resolved, or the investigator assesses it as chronic 
or stable. 
5 
The follow-up visit will be a phone call approximately 4 weeks after Visit 5 for subjects that complete the study and immediately start receiving commercial 
deflazacort or another corticosteroid. The follow-up will be an office visit for subjects that are tapering off deflazacort to return study drug and for site 
collection of any AEs and will occur 4-weeks after last dose of study drug.  
6 
Hematology assessments include hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and mean 
corpuscular hemoglobin concentration, mean platelet volume, red blood cell distribution width, neutrophils (% and absolute), total lymphocytes (% and 
absolute), monocytes (% and absolute), eosinophils (% and absolute), basophils (% and absolute), and platelets. 
7 
Chemistry assessments include sodium, potassium, chloride, bicarbonate, blood urea nitrogen (urea), creatinine, uric acid, protein (total), albumin, bilirubin 
(total), aspartate transaminase, alanine transaminase, gamma glutamyl transpeptidase, alkaline phosphatase, lactase dehydrogenase, glucose (fasting), 
hemoglobin A1c, calcium, phosphate, magnesium, creatine kinase, cholesterol, high density lipoproteins, low density lipoproteins (calculated), and 
triglycerides. 
8 
Only for women of child-bearing potential. 
9 
Ophthalmological examination includes a glaucoma assessment, cataract assessment, and intraocular pressure measurement. 
10 If possible, both X-ray and DEXA should be performed; however, only an X-ray or DEXA is acceptable if the other technology is not available or prohibited 
per local ethical/regulatory decree. 
11 The pre-dose blood draw will be taken within 2 hours before dosing. For timepoints up to 2-hours post dose, a window of ± 10 minute will be allowed for blood 
collection. From 4 hours to 6 hours post samples, a window of ± 30 minutes will be allowed. 
12 Efficacy and PD assessments will be performed post-daily-dose at each clinic visit, except for the baseline visit (Visit 1). At screening and baseline visits, the 
ability to ascend 4 stairs must be ≥2.5 and ≤8 seconds. In addition, the 4-stair climb will be performed twice at each visit. The second test should be done a 
minimum of 5 minutes after the prior test (or any other physical activity). The two 4-stair climb results must be within 20% of one another. If they are not the 
Medical Monitor should be contacted. 
13 Biomarker testing (bone health assays) include bone alkaline phosphatase (BAP), Beta-CrossLaps (Beta-CTx), insulin-like growth factor-1 (IGF1), 
parathyroid hormone (PTH) intact, aldosterone, and vitamin D (Serum 25-hydroxyvitamin D3). 
14 INQoL will be performed before the first dose at baseline and after 26 weeks of treatment, when possible.  
15 Dixon MRI and T2 MRI will be conducted at a subset of sites that have been pre-qualified by a central imaging vendor to perform this assessment. To be pre-
qualified, a site must have access to whole-body scanner and appropriate personnel and must have been trained on the procedure for data acquisition. MRI 
data will be analyzed centrally. 

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PROTOCOL IDENTIFIERS AND STUDY PERSONNEL 
 
Study Number 
PTCEMF-GD-004 
Therapeutic Area  
Genetic Disorders - Limb-Girdle Muscular Dystrophy 
Type 2I 
PTC Therapeutics Substance Identifier Deflazacort (Emflaza)  
IND Number  
142275 
EudraCT Number  
2018-004740-36 
Included in clinical trials.gov Database NCT03783923 
Protocol Number 
PTCEMF-GD-004 
Protocol Version  
4.0 
Protocol Version Date 
25 March 2020 
Protocol Phase 
N/A 
Protocol Title 
A Multicenter Open-Label Study on the Safety and 
Efficacy of Deflazacort (Emflaza®) in Subjects with 
Limb-Girdle Muscular Dystrophy 2I (LGMD2I) 
 
 
PTC Clinical Lead 
PTC Therapeutics, Inc.  
100 Corporate Court 
South Plainfield, NJ  07080 USA 
Telephone (office):
E-mail: 
 
 
PTC Medical Monitor 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Telephone (office): 
Email: 
 
 
PTC Biostatistician 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Telephone:
 
E-mail:
 
 
PTC Clinical Operations 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Telephone:
Email: 

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PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
PTC Therapeutics, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
PTC Therapeutics, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
PTC Therapeutics, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
PTC Therapeutics, Inc. 
 
 
 
 
 
 

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PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE 
 
 
I have read the protocol document and, on behalf of my institution, agree to comply with the 
protocol and all applicable regulations. 
 
 
 
 
Principal Investigator 
 
Date 
 
 
 
Institution: 
 
Address: 
 
City: 
 
State/Province: 
 
Country: 
 
Phone: 
 
Fax: 
 
E-mail: 
 
 
 
 

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TABLE OF CONTENTS 
SYNOPSIS 3 
PROTOCOL IDENTIFIERS AND STUDY PERSONNEL ........................................................................ 11 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES ............................................................. 12 
PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE ........................................................... 13 
TABLE OF CONTENTS .................................................................................................................. 14 
LIST OF TABLES .......................................................................................................................... 16 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................. 17 
1 
INTRODUCTION ......................................................................................................... 19 
1.1 
Background ............................................................................................................... 19 
1.2 
Deflazacort (Emflaza) ................................................................................................ 20 
1.3 
Benefit/Risk Profile ................................................................................................... 20 
2 
STUDY OBJECTIVES AND ENDPOINTS ......................................................................... 21 
2.1 
Objectives ................................................................................................................. 21 
2.1.1 
Primary Objective ..................................................................................................... 21 
2.1.2 
Secondary Objectives ................................................................................................ 21 
2.1.3 
Exploratory Objective ................................................................................................ 21 
2.2 
Endpoints ................................................................................................................. 22 
2.2.1 
Primary Endpoint ...................................................................................................... 22 
2.2.2 
Secondary Endpoints ................................................................................................. 22 
2.2.3 
Exploratory Endpoints ............................................................................................... 22 
3 
STUDY DESIGN .......................................................................................................... 23 
3.1 
Overall Design ........................................................................................................... 23 
3.2 
Scientific Rationale for Study Design .......................................................................... 24 
3.3 
Justification of Dose .................................................................................................. 29 
3.4 
Subject Transition Procedures: Version 3.0 to Version 4.0 .......................................... 30 
3.5 
Study Completion ..................................................................................................... 30 
4 
STUDY POPULATION ................................................................................................. 31 
4.1 
Overview .................................................................................................................. 31 
4.2 
Inclusion Criteria ....................................................................................................... 31 
4.3 
Exclusion Criteria ...................................................................................................... 31 
4.4 
Screen Failures .......................................................................................................... 32 
5 
ENROLLMENT PROCEDURES ...................................................................................... 32 
5.1 
Source and Number of Subjects ................................................................................. 32 
5.2 
Screening .................................................................................................................. 32 
6 
INVESTIGATIONAL PRODUCT(S) ................................................................................. 32 
6.1 
Investigational Product(s) Administration .................................................................. 32 
6.1.1 
Investigational Product Description ........................................................................... 32 
6.1.1.1 
Deflazacort 
32 
6.1.2 
Dosing and Administration ........................................................................................ 32 
6.1.2.1 
Weight Bands 
33 
6.1.2.2 
Safety Criteria for Adjustment or Stopping Dosing ...................................................... 33 
6.1.3 
Return of Study Drug ................................................................................................. 37 
6.1.4 
Overdose or Inadvertent Exposure Precautions .......................................................... 37 

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6.2 
Preparation/Handling/Storage/Accountability ........................................................... 37 
6.2.1 
Acquisition and Accountability .................................................................................. 37 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .................................................... 37 
6.2.3 
Storage and Stability ................................................................................................. 37 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................... 37 
6.4 
Study Intervention and Compliance ........................................................................... 38 
6.5 
Concomitant Therapy ................................................................................................ 38 
6.5.1 
Rescue Medication .................................................................................................... 38 
6.5.2 
Prohibited Medications ............................................................................................. 38 
7 
INVESTIGATIONAL PRODUCT DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................ 40 
7.1 
Discontinuation of Study Medication ......................................................................... 40 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................ 41 
7.3 
Lost to Follow-up ...................................................................................................... 41 
8 
STUDY ASSESSMENT AND PROCEDURES .................................................................... 41 
8.1 
Schedule of Events and Study Procedures .................................................................. 41 
8.2 
Efficacy Assessments ................................................................................................. 47 
8.3 
Pharmacokinetic Assessments ................................................................................... 47 
8.4 
Adverse Events and Serious Adverse Events ............................................................... 47 
8.4.1 
Definition of an adverse events ................................................................................. 47 
8.4.2 
Definition of a serious adverse events ....................................................................... 49 
8.4.3 
Unexpected Adverse Events ...................................................................................... 50 
8.4.4 
Eliciting adverse event information............................................................................ 50 
8.4.5 
Recording Serious and Non‑serious Adverse Events ................................................... 50 
8.4.6 
Describing adverse event relationship to study drug .................................................. 50 
8.4.7 
Grading of Severity of Adverse Event ......................................................................... 51 
8.4.8 
Adverse Event Reporting ........................................................................................... 52 
8.4.9 
Serious Adverse Event Reporting ............................................................................... 52 
8.4.10 
Contraception 53 
8.4.11 
Reporting Pregnancy ................................................................................................. 54 
8.4.12 
PTC Therapeutics Adverse Event Reporting Requirement ........................................... 54 
8.4.13 
Safety Monitoring ..................................................................................................... 54 
9 
STATISTICAL CONSIDERATIONS .................................................................................. 55 
9.1 
Statistical Hypothesis ................................................................................................ 55 
9.2 
Sample Size Determination ........................................................................................ 55 
9.3 
Population for Analyses............................................................................................. 55 
9.3.1 
Full/Safety Population ............................................................................................... 55 
9.3.2 
Pharmacokinetic Population ...................................................................................... 55 
9.4 
General Statistical Considerations ............................................................................. 55 
9.5 
Specific Statistical Analyses ....................................................................................... 56 
9.5.1 
Study Conduct 56 
9.5.2 
Subject Disposition .................................................................................................... 56 
9.5.3 
Demographics and Baseline Characteristics ................................................................ 56 
9.5.4 
Study Treatment and Extent of Exposure ................................................................... 56 

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9.5.5 
Prior and Concomitant Medication ............................................................................ 56 
9.5.6 
Analyses of Primary Endpoints .................................................................................. 56 
9.5.7 
Analyses of Secondary Endpoints for Safety ............................................................... 56 
9.5.7.1 
Adverse Events 
57 
9.5.7.2 
Laboratory Abnormalities .......................................................................................... 57 
9.5.7.3 
Other Safety Assessments.......................................................................................... 57 
9.5.8 
Analyses of Secondary Endpoints for Pharmacokinetics ............................................. 57 
9.5.9 
Exploratory Endpoints ............................................................................................... 57 
9.5.10 
Subgroup Analyses .................................................................................................... 58 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ..................... 58 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ............................................ 58 
10.1.1 
Institutional Review Board/Independent Ethics Committee ....................................... 58 
10.1.2 
Informed Consent Process ......................................................................................... 59 
10.1.3 
Study Discontinuation and Closure ............................................................................ 59 
10.1.4 
Confidentiality and Privacy ........................................................................................ 59 
10.1.5 
Clinical Monitoring .................................................................................................... 60 
10.1.6 
Quality Assurance and Quality Control ....................................................................... 60 
10.1.7 
Data Handling and Record Keeping ............................................................................ 61 
10.1.8 
Protocol Deviations ................................................................................................... 61 
10.1.9 
Publication and Data Sharing Policy ........................................................................... 62 
10.2 
Additional Considerations ......................................................................................... 63 
10.2.1 
Public Notification of Study Conduct .......................................................................... 63 
10.2.2 
Communications with Regulatory Authorities ............................................................ 63 
10.3 
Protocol Amendment History .................................................................................... 63 
11 
REFERENCES .............................................................................................................. 70 
 
LIST OF TABLES 
Table 1. 
Incidence of TEAEs in Deflazacort and Placebo Treatment Arms in DMD Subjects ..... 28 
Table 2. 
Weight-based Dosing Summary ............................................................................... 33 
Table 3. 
CYP3A Inhibitors ..................................................................................................... 39 
Table 4. 
CYP3A Inducers ....................................................................................................... 39 
Table 5. 
Taper paradigm per weight band............................................................................. 40 
Table 6. 
Schedule of Events .................................................................................................. 42 
Table 7. 
Relationship of Study Drug to Adverse Event Relationship ....................................... 51 
Table 8. 
Grading of Adverse Event Severity Grade ................................................................ 51 
Table 9. 
Investigator Site Requirements for Reporting Adverse Events .................................. 52 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
21-desDFZ 
21-desacetyl deflazacort 
6MWD 
6-minute walk distance 
α-DG 
α-dystroglycan 
AE 
Adverse event 
AUC 
Area under the concentration curve 
BAP 
Bone alkaline phosphatase 
Beta-CTx 
Beta-CrossLaps 
CI 
Confidence interval 
CL/F 
Clearance  
Cmax 
Maximum concentration 
CRF; (eCRF) 
Case report form; electronic CRF 
CRO 
Contract research organization 
CTCAE 
Common terminology criteria for adverse events 
CYP 
Cytochrome P450 
DEXA 
dual-energy X-ray absorptiometry 
DMD 
Duchene muscular dystrophy 
ECG 
Electrocardiogram 
ET 
Early termination 
FKRP 
Fukutin-related protein gene 
FDA 
Food and Drug Administration  
FVC 
Forced vital capacity 
GCP 
Good clinical practice 
HbA1c 
Hemoglobin A1c 
HCG 
Human chorionic gonadotropin 
HPA 
Hypothalamicpituitary-adrenal 
ICH 
International Council for Harmonization 
IEC 
Institutional Ethics Committee 
IGF1 
Insulin-like growth factor-1 
INQoL 
Individualized Neuromuscular Quality of Life 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
ITT 
Intent to treat 
LC-MS/MS 
Liquid chromatography with tandem mass spectrometry 
LGMD 
Limb-girdle muscular dystrophy 
LGMD2 
Limb-girdle muscular dystrophy type 2 
LGMD2I 
Limb-girdle muscular dystrophy type 2I 
LoA 
Loss of ambulation 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEP 
Maximal expiratory pressure 
MHC 
Major histocompatibility complex 
MIP 
Maximal inspiratory pressure 
MMRM 
Mixed-effect model with repeated measures 
MRI 
Magnetic resonance imaging 
PD 
Pharamcodynamic 
PK 
Pharmacokinetic 
PT 
Preferred term 
PTH 
Parathyroid hormone 
RSI 
Reference safety information 
SAE 
Serious adverse event 
SOC 
System organ class 

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Term 
Definition 
T2 
Transverse relaxation time 
T1/2 
Terminal half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
Vz/F 
Volume of distribution 
WOCBP 
Women of child bearing potential 
λz 
(Time)-1 
 
 
 

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1 
INTRODUCTION 
1.1 
Background 
Initially described as a clinical phenotype, limb-girdle muscular dystrophies (LGMDs) are now 
recognized as a heterogeneous group of rare genetic myopathies with many subtypes categorized 
by disease, gene, and inheritance (Khadilkar 2018). The limb-girdle is the bony structure surrounding 
the shoulder and hip joints. LGMD usually manifests in the proximal muscles (closest to the center of 
the body) around the hips and shoulders and is characterized by progressive muscle wasting, 
resulting from replacement of muscle tissue by fibrosis and fat. LGMDs vary in severity and may 
affect persons at all ages. The LGMDs are classified into 2 main groups depending on the inheritance 
pattern: LGMD type 1 are autosomal dominant and LGMD type 2 (LGMD2) are autosomal recessive 
diseases. 
LGMD type 2I (LGMD2I) is a subtype of the type 2 LGMD and is caused most frequently by a 
homozygous founder mutation (826C>A; p L276I) in the fukutin-related protein (FKRP) gene 
(Brockington 2001, Willis 2014, Wang 2018).  
It is difficult to determine the prevalence of LGMD due to its features vary and overlap with those of 
other muscle disorders. The estimated prevalence of LGMD ranges from 0.07 per 100,000 to 2 per 
100,000 individuals (Narayanaswami 2014, Deenen 2015, Mah 2016). LGMD2I may be one of the 
more common forms of LGMD (Moore 2006, Kang 2007). A small study indicated that about 4% of 
patients in the United States with LGMD have LGMD2I (Moore 2006). The current population in the 
United States is about 327,571,179; hence, up to about 400 individuals in the United States have 
LGMD2I. A higher prevalence of LGMD2I has been reported in northern European countries (Sveen 
2006). 
Common clinical symptoms of LGMD2I include proximal muscle weakness, calf hypertrophy, 
elevated serum creatine kinase levels, and cardiac and pulmonary involvement (Wang 2018). The 
clinical spectrum of LGMD2I is heterogeneous, and includes asymptomatic mutation carriers, a 
severe early-onset phenotype with loss of ambulation in teens as in Duchenne muscular dystrophy 
(DMD), and a Becker muscular dystrophy-like course with late-onset age and slow progression (de 
Paula 2003, Schwartz 2005). Dilated cardiomyopathy and restrictive respiratory insufficiency have 
been reported frequently in patients with LGMD2I (Poppe 2003, Bourteel 2009). The age at onset of 
LGMD2I ranged from 2 to 50 years (Boito 2005). 
The pathogenesis of FKRP mutations appears primarily to be linked to the absence of glycosylation 
of α-dystroglycan (α-DG), an extracellular component of the dystrophin glycoprotein complex, 
resulting in disruption of laminin binding and instability of the dystrophin-glycoprotein complex in 
skeletal muscle (Brown 2004a). The dystrophin-glycoprotein complex is important for the structural 
stability of muscle membrane during cycles of contraction and relaxation (Muntoni 2011, Wang 
2018). Phenotypic severity of LGMD2I is correlated to the degree of the reduction of α-DG (Brown 
2004b). 

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In patients homozygous for the 826C>A missense mutation, patients generally exhibit milder and 
late-onset muscular dystrophy, whereas the compound heterozygous 826C>A mutation is associated 
with more severe and early-onset type of muscular dystrophy phenotypically related to DMD (Sveen 
2006, Stensland 2011, Wang 2018). Intrafamilial variability is common and suggests other factors in 
addition to FKRP mutation may influence phenotype (Boito 2005, Darin 2007).  
Current Treatments 
No approved pharmacological treatment is currently available for LGMD2I, although aggressive 
supportive care including physical therapy and cardiac care is considered essential (Narayanaswami 
2014).  
1.2 
Deflazacort (Emflaza) 
Deflazacort (Emflaza®) is a corticosteroid used as an anti-inflammatory and immunosuppressive 
agent. Pharmacologically, it is an inactive ester pro-drug which is metabolized rapidly to the active 
drug 21-desacetyl-deflazacort (21-desDFZ), which acts through the glucocorticoid receptor to exert 
its anti-inflammatory and immunosuppressive effects. Deflazacort has an extensive exposure history 
as an approved drug in many countries outside of the United States. The side effect profile of 
deflazacort in patients with DMD aged ≥5 years is well characterized and consistent with that of the 
corticosteroid class of drugs. 
On February 9, 2017, deflazacort was approved by the U.S. Food and Drug Administration (FDA) as a 
treatment for patients aged ≥5 years with DMD and as a treatment for patients ≥2 years with DMD 
on June 7, 2019 (https://www.emflaza.com/). 
PTC Therapeutics has decided to initially investigate the use of deflazacort in LGMD by focusing on 
its affects in LGMD2I. The choice of LGMD2I was based upon the fact that several case reports have 
indicated benefit of corticosteroid use in this subtype of LGMD and other muscular dystrophies 
(Angelini 2007, Darin 2007, Lin 2007, Svahn 2015, Wang 2018). PTC Therapeutics has also taken into 
consideration advice from clinical experts who treat patients with LGMD, including LGMD2I. 
Multiple lines of evidence indicate that the use of deflazacort may show treatment benefit in 
LGMD2I. Several clinical and preclinical studies found that the immune system is involved in the 
pathology of LGMD2I and that corticosteroid therapy was associated with clinical benefit (see 
Section 3.2 for greater description) (Darin 2007, Lin 2007, Svahn 2015, Wang 2018). 
1.3 
Benefit/Risk Profile 
Currently, treatment options for LGMD2I are limited. LGMD2I is a devastating disease and patients 
with this form of muscular dystrophy are at high risk for developing respiratory failure and 
cardiomyopathy (Narayanaswami 2014). Respiratory failure constitutes a major comorbidity, 
interfering with daytime cognitive function and negatively affecting quality of life (Narayanaswami 
2014). In addition, ventilatory and oropharyngeal weakness can threaten survival through the risk of 
upper airway obstruction and/or bellows failure (Narayanaswami 2014). 

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Deflazacort carries the risks common to all corticosteroids, including immune suppression, 
decreased bone density, and endocrine insufficiency (see Emflaza® [deflazacort] Prescribing 
Information). 
No definitive therapies are available for LGMD2I, and only a few clinical studies have assessed 
therapies for the treatment of LGMD2I (Narayanaswami 2014). To date no randomized, controlled 
clinical studies have been performed that evaluate treatment effect of corticosteroids in this patient 
population. Several case study reports suggest that corticosteroid therapy may improve the 
symptoms of the disease and possibly delay disease progression (Darin 2007, Svahn 2015, Wang 
2018). In addition, preclinical studies in a LGMD2I mouse model found prednisolone treatment 
improved muscle pathology with significant reduction in muscle degeneration and enhanced 
functionality of α-DG (Wu 2016).  
Given the limited treatment options to slow the deterioration of muscle function in LGMD2I and 
findings from preclinical studies and case reports, it is reasonable to consider the use of deflazacort 
in treating patients with LGMD2I. Moreover, deflazacort has well established efficacy in DMD, and 
has been shown to delay DMD disease progression in patients (Bello 2015, McDonald 2018). The 
safety profile of corticosteroids is well established in multiple indications, and safety concerns can 
be managed through monitoring, including bone health (as assessed by incidence of fracture and 
dual energy X-ray absorption [DEXA]) scans. Hence, the potential benefits of this study outweigh the 
potential risks to study subjects. 
2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
2.1.1 
Primary Objective 
1. 
To evaluate the efficacy of deflazacort as measured by muscle function in subjects with 
LGMD2I 
2.1.2 
Secondary Objectives 
1. 
To evaluate the effects of deflazacort on pulmonary function in subjects with LGMD2I  
2. 
To evaluate the pharmacokinetic (PK) profile of deflazacort in subjects with LGMD2I 
3. 
To evaluate safety of deflazacort in subjects with LGMD2I 
2.1.3 
Exploratory Objective 
1. 
To evaluate the predictive value of global T2 MRI as a measure of efficacy of deflazacort 
in subjects with LGMD2I 
2. 
To evaluate quality of life by the Individualized Neuromuscular Quality of Life (INQoL) 
questionnaire in subjects with LGMD2I 

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2.2 
Endpoints 
2.2.1 
Primary Endpoint 
The primary efficacy endpoint is: 
1. 
Change from baseline in time to climb 4 stairs after 26 weeks of treatment 
2.2.2 
Secondary Endpoints  
1. 
Secondary efficacy endpoints 
a. 
Change from baseline in forced vital capacity (FVC) after 26 weeks of treatment 
b. 
Change from baseline in 2-minute walk test after 26 weeks of treatment 
c. 
Change from baseline in time to up and go after 26 weeks of treatment 
d. 
Change from baseline to time to descent 4 stairs after 26 weeks of treatment 
e. 
Change from baseline in time to run/walk 10 meters after 26 weeks of treatment 
f. 
Change from baseline in maximal inspiratory pressure (MIP) and maximal 
expiratory pressure (MEP) after 26 weeks of treatment 
g. 
Change from baseline in hand-held myometry after 26 weeks of treatment 
h. 
Change from baseline in global T2 relaxation time of selected upper and lower limb 
muscles after 26 weeks of treatment 
2. 
Safety profile characterized by type, frequency, severity, timing, and relationship to 
study drug of any adverse events (AEs), laboratory abnormalities, electrocardiogram 
(ECG) abnormalities, ophthalmologic abnormalities, DEXA to evaluate bone density, 
and/or X-ray to assess spine fracture 
3. 
Pharmacokinetic assessments at baseline and after 13 weeks of treatment 
2.2.3 
Exploratory Endpoints 
1. 
Change from baseline in muscular fat using Dixon magnetic resonance imaging of 
selected lower limb muscles after 26 weeks of treatment 
2. 
Change from baseline in the INQoL questionnaire in subjects with LGMD2I after 26 weeks 
of treatment 

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3 
STUDY DESIGN 
3.1 
Overall Design 
Study PTCEMF-GD-004 is a prospective, open label study designed to evaluate the safety and 
efficacy of deflazacort in subjects with LGMD2I. 
Approximately, 30 subjects, ≥18 years old, with LGMD2I will be enrolled in the study. Most subjects 
enrolled will have a screening visit and 3 additional visits (after 1, 13, and 26 weeks of treatment: 
see section 3.4). A follow-up visit will be a phone call approximately 4 weeks after the final study 
visit for subjects that complete the study and immediately start receiving commercial deflazacort or 
another corticosteroid. The follow-up will be an office visit for subjects that are tapering off 
deflazacort to return study drug and for site collection of any AEs and will occur 4-weeks after last 
dose of study drug. At Week 3, a member of the site staff will follow-up with the subject to assess 
safety.  
At the Screening Visit inclusion/exclusion criteria, demographics and medical/surgical history will be 
assessed (see Table 6, Schedule of Events for details). In addition, genotyping to confirm a subject 
carries a mutation in the FKRP gene may be performed for subjects lacking documentation of the 
FKRP mutation. All subjects must sign an informed consent prior to any study procedures being 
conducted. 
Subjects that complete the screening period assessments and meet all inclusion/exclusion criteria 
will be enrolled at Visit 1 (baseline Visit) to a target dose of 0.6 mg/kg/day oral deflazacort. 
Note: Doses are described as target doses, resulting from the possibility of variation of ±20% 
from the target dose due to the available tablet strengths and changes in subject weight.  
Study medication will be assigned according to the subject’s weight. Three weight bands will be 
utilized and automatically assigned via an Interactive Response Technology (IRT) system. Unless an 
occurrence of an AE requires otherwise, the investigator is encouraged to maintain the same dose 
through the first 13 weeks of treatment due to safety or tolerability considerations; the dose can be 
changed to the next lower weight-band if needed (see Section 6.1.2.1 for weight band chart).  
Screening procedures must occur within 6 weeks (42 days) prior to the baseline visit (Visit 1). 
Any screening procedures completed within and including 7 days of Visit 1, except for 4-stair climb, 
can serve as baseline and do not have to be repeated at Visit 1. At baseline and all other visits, the 4-
stair climb will be performed twice. The second 4 stair climb test should be done a minimum of 5 
minutes after the prior test, or any other physical activity. The two 4-stair climb results must be 
within 20% of one another. If they are not the Medical Monitor should be contacted. 
At the baseline visit, all baseline procedures must be performed, and the pre-dose PK sample must 
be drawn prior to the first dose of study medication. Study medication will then be administered, 
and the remainder of the PK samples drawn according to the PK draw schedule (ie, 0.5, 1, 2, 4, and 6 
hours post-dose). Baseline efficacy, MRI, and safety will also be assessed. The baseline visit can be 
conducted over two consecutive days.  
A member of the site staff will follow-up with the subject 3 weeks from the baseline visit to assess 
safety.  

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Subjects will return to the site after 13 weeks (Visit 2/4) for safety, efficacy, PK, and MRI 
assessments. At Visit 2, the daily dose of study drug will be administered following the pre-dose PK 
blood draw.  
For the remaining visits, study drug will be administered at home on the day of the in-clinic visit. 
After 26 weeks of treatment (Visit 3/5/ET) safety, efficacy, and MRI will be evaluated.  
At the end of the study, subjects have the following 3 options: 1) taper off deflazacort; 2) in 
conversation with their healthcare provider, they could switch to a commercially available version of 
deflazacort; or 3) in conversation with their healthcare provider, they could switch to another 
commercially available corticosteroid. If it is determined that a subject will discontinue the study in 
between visits, the subject should return at the earliest convenience for an early termination visit, 
following completion of any required study medication assessments. Subjects who terminated 
early/ discontinued from the study and are tapering off deflazacort will be followed until the 
tapering is complete, and a follow-up visit will occur about 4 weeks after termination. In case of 
discontinuation due to an AE, the AE should be followed up by the investigator until it is resolved, or 
the investigator assesses it as chronic or stable. 
The follow-up visit will be a phone call about 4 weeks after the final clinic visit for subjects that 
complete the study and immediately start receiving commercial deflazacort or switch to another 
corticosteroid. The follow-up will be an office visit for subjects that are tapering off deflazacort to 
return study drug and for site collection of any AEs and will occur approximately 4 weeks after final 
dose of deflazacort. 
3.2 
Scientific Rationale for Study Design  
This study is designed to evaluate the efficacy and safety of deflazacort in the treatment of patients 
with LGMD2I. 
At present, no therapies have clearly been demonstrated to slow progression of muscle weakness 
for LGMDs. A limited number of case reports and small studies have assessed the use of 
corticosteroid treatment in LGMD, and have shown some potential benefit of corticosteroid use in 
patients with certain subtypes of LGMD including LGMD2C, LGMD2D, LGMD2E; and LGMD2I, 
LGMD2L, LGMD2M (Pegoraro 1993, Angelini 1998, Godfrey 2006, Darin 2007, Baumeister 2009, 
Wong-Kisiel 2010, Nigro 2014, Svahn 2015, Carotti 2017, Wang 2018). Mouse models have also 
shown benefit of corticosteroid treatment in certain LGMDs (Wu 2016, Quattrocelli 2017).  
Several case reports have suggested the positive benefit of long-term corticosteroid therapy in 
patients with LGMD2I (Darin 2007, Lin 2007, Svahn 2015, Wang 2018). These studies also suggest 
that a treatment effect should be observable within a 26-week period. 
• 
Darin et al. (2007) found LGMD2I was associated with inflammation with up-regulation of 
major histocompatibility complex (MHC) class 1 in muscle biopsies of 2 patients with 
LGMD2I (Darin 2007). In both patients, after 4 to 6 months of treatment with 
prednisolone (initiated daily dose of 0.35 mg/kg/day) significant improvement in muscle 
strength and motor function were observed.  

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o 
The first patient (age 16 years), prior to prednisolone treatment, could only walk 
short distances indoors without support and had great difficulty rising from a chair. 
After 6 months of treatment, no further deterioration in muscle function was 
observed, and the patient showed improvement in muscle strength, motor 
function, and time tests that were maintained over time. The patient remained on 
corticosteroid therapy >4 years. Over this time the dose of corticosteroid ranged 
from 0.32 to 0.37 mg/kg/day. 
o 
The second patient (age 10 years), prior to prednisolone treatment initiation, had 
great difficulty rising from the ground after a fall and rising from a chair, and could 
only do these tasks with support. Following 4 months of treatment, the patient 
could rise from the floor easier and without support and could swim and stand on 1 
leg for a longer period of time. The prednisolone therapy was decreased over time. 
The treatment effects were stable until 2 years after onset of treatment, which was 
associated with reduction of the prednisolone dosage to 0.17 mg/kg/day. The 
patient remained on corticosteroid therapy >4 years. 
• 
Lin et al. (2007) identified a female patient (age 2 years and 3 months) with LGMD2I who 
had progressive shoulder and pelvic muscle weakness and became unable to walk (Lin 
2007). The patient was treated with prednisolone (20 mg/day). The corticosteroid 
therapy was associated with improvement of the clinical and pathological symptoms of 
the disease. Her muscle weakness gradually improved within 3 months and she was again 
ambulant at the age of 2 years and 6 months and could run and dance for the following 5 
years. 
• 
Svahn et al. (2015) described a woman (age 20 years) with LGMD2I clinical findings 
suggestive of an inflammatory myopathy who showed significant clinical improvement 
using corticosteroid, azathioprine, and intravenous immunoglobulin treatments (Svahn 
2015). Oral prednisolone was started at a daily dose of 50 mg resulting in a reduction in 
myalgia, which was subsequently tapered to 25 mg/day due to adverse side effects of 
tremor and drowsiness. Over approximately a year, prednisolone was tapered to 12 
mg/day. A stable clinical improvement in walking distance of 2000 meters was seen with 
therapy and the patient was able to go back to work.  
• 
Wang et al. (2018) identified 2 patients from unrelated families with LGMD2I (Wang 
2018). One patient (age 15 years) developed progressive proximal muscle weakness of 
the lower leg at age 6 years and by age 10 had difficulty climbing stairs. The patient had 
mild inflammatory involvement within the endomysial connective tissues by muscle 
biopsy. The patient was treated with prednisolone (0.75 mg/kg/day). At a second visit 8 
months following the start of therapy, the patient showed no further deterioration in 
muscle strength or 6-minute walk distance (6MWD) compared with prior to therapy. 

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PTC Therapeutics has decided to initially investigate the use of deflazacort in LGMD by focusing on 
its affects in LGMD2I. The choice of LGMD2I was based upon the fact that several case reports have 
indicated benefit of corticosteroid use in this subtype of LGMD and other muscular dystrophies 
(Angelini 2007, Darin 2007, Lin 2007, Svahn 2015, Wang 2018). PTC Therapeutics has also taken into 
consideration advice from clinical experts who treat patients with LGMD, including LGMD2I. 
Several lines of clinical and preclinical evidence indicate that the use of deflazacort may show 
treatment benefit in LGMD2I. A number of case study reports have demonstrated good clinical 
responses to corticosteroid therapy in patients with LGMD2I. Darin et al (2007) reported that muscle 
strength and motor function were significantly improved in two patients with LGMD2I after 
prednisolone treatment for 4 to 6 months (Darin 2007). They also reported that the immune system 
was involved in the pathology of LGMD2I based on muscle biopsies showing inflammation with up-
regulation of MHC class 1. Svahn et al (2015) described a patient with LGMD2I who had clinical 
findings suggestive of an inflammatory myopathy who showed significant clinical improvement 
using corticosteroid, azathioprine and intravenous immunoglobulin treatments (Svahn 2015). Wang 
et al. (2018) identified a member of a family with mild inflammatory involvement within the 
endomysial connective tissues by muscle biopsy that was determined to result from LGMD2I (Wang 
2018). They found that following prednisolone therapy no further deterioration in muscle strength 
was observed in this patient. Moreover, corticosteroid treatment was associated with lack of 
deterioration in 6MWD, compared with 6MWD prior to therapy.  
Preclinical studies support the use of deflazacort in the treatment of LGMD2I. Murine models of 
LGMD2I have shown that corticosteroid treatment is associated with a reduction in the 
fibroinflammatory process and increases in the proportion of functionally glycosylated α-DG (Wu 
2016, Quattrocelli 2017). Wu et al. (2016) generated a mouse model for LGMD2I that contains a 
P448L mutation and exhibits a typical muscular dystrophy phenotype observed in most LGMD2I 
muscle, including a significant reduction in functional glycosylation of α-DG in muscles and mild 
cardiac muscle pathology without an apparent involvement of the central nervous system (Wu 
2016). Skeletal muscles of this mouse model undergo progressive degeneration, particularly in the 
diaphragm, although the life span of the mice can by >16 months. Wu et al. found that P448L-
mutant mice administered 2 mg/kg daily or 5 mg/kg daily or twice weekly of prednisolone for 3 
months compared with saline treated controls showed increased muscle strength as measured by 
forelimb and hindlimb grip strength, although this did not reach statistical significance. They also 
found that both daily and twice weekly 5 mg/kg prednisolone showed clear improvement in muscle 
pathology with a significant reduction in degenerating fibers compared with controls. In addition, 
treatment with 5 mg/kg of prednisolone both daily or twice a week greatly reduced inflammation, 
with almost elimination of focal accumulation of infiltrates, and a significant reduction in the 
number of hypertrophic fibers (>80 µm in diameter) compared with saline treated controls was also 
observed. 

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The use of corticosteroids for the treatment of LGMD2I is further supported by the findings that 
steroids improved FKRP-mediated muscular dystrophy in a zebrafish model of LGMD2I (Serafini 
2018). Serafini et al. generated a LGMD2I model in zebrafish by expression of a FKRP transgene that 
contained the human fkrp (L276I) open reading frame under a heat-shock promoter in fish that did 
not have a functional fkrp gene (ie, fkrp-/fkrp-) (Serafini 2018). Zebrafish expressing the transgene 
had overall pathology consistent with LGMD2I (Serafini 2018). Using the LGMD2I zebrafish model, 
Serafini et al. performed an unbiased double-blind screen of the FDA-approved Prestwick compound 
library (Version 2). Out of the 1,120 total compounds in the library, 20 unique compounds were 
identified that ameliorated FKRP-dependent pathologies, with steroids being one of the most 
common group (Serafini 2018). 
Deflazacort has been shown to have clinical benefit in other muscular dystrophies. In Duchenne 
muscular dystrophy DMD, deflazacort treatment tended to result in a greater delay in milestone 
transitions compared with prednisolone/prednisone therapy (Bello 2015, McDonald 2018). In the  
Cooperative International Neuromuscular Research Group Duchenne Natural History Study, 
deflazacort had a >2-year-later median age of loss of ambulation (LoA) (13.9 vs. 11.2 years, 
respectively) and a significantly lower yearly risk of LoA (Cox regression, 0.498 vs. 0.294; P<0.001) 
than prednisolone/prednisone (Bello 2015). Deflazacort was also associated with a greater delay in 
loss of the ability to rise from supine and of hand-to-mouth function compared with 
prednisolone/prednisone (P values ≤0.0114) (Bello 2015). Deflazacort has also been found to show 
benefit in patients with LGDM2E. A case report of two siblings with homozygous β-sarcoglycan gene 
mutation (S114F), consistent with LGMD2E, underwent a course of deflazacort (Wong-Kisiel 2010). 
At 22 months of drug therapy, both patients had stable or improved strength testing. Despite the 
severe phenotype, deflazacort had a beneficial effect on slowing disease progression in LGMD2E, 
similar to that seen in DMD. 
The decision to evaluate deflazacort for the treatment of LGMD2I is based on the prior clinical 
evidence of the benefit of corticosteroid use in LGMD2I and other muscular dystrophies, and the 
potential for greater efficacy and tolerability observed with deflazacort compared with 
prednisolone/prednisone.  
Common deflazacort-related AEs in DMD 
The safety of deflazacort has been studied in semi-chronic to chronic studies in both adults and 
children. Deflazacort-associated AEs are consistent with known AEs of the glucocorticoid class, 
including weight gain, cushingoid features, insulin resistance, diabetes, behavioral side-effects, 
osteopenia, risk of fractures, and cataracts (Table 1) (Emflaza [deflazacort] Prescribing Information , 
Matthews 2016, Calcort 6 mg Tablet SmPC 2018). The common AEs across approved indication of 
deflazacort in Europe and the United States can be found in the prescribing information (Emflaza 
[deflazacort] Prescribing Information , Calcort 6 mg Tablet SmPC 2018).  
Of note, in 1 study deflazacort was associated with less cushingoid face than prednisone (P value = 
0.0385; (Griggs 2016)). A beneficial difference in weight gain versus other glucocorticoids is seen 
early in treatment with deflazacort and is maintained for up to 1 year. This lessened weight gain is 
important in this patient population since diminished strength from the disease is worsened by 
weight gain (Griggs 2016). 

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Table 1. 
Incidence of TEAEs in Deflazacort and Placebo Treatment Arms in DMD 
Subjects  
Preferred Term 
Deflazacort 0.9 mg/kg/day 
(N=93) 
n (%) 
Placebo  
(N=61) 
n (%) 
Number of subjects with at least 1 TEAE 
76 (81.7) 
46 (75.4) 
Cushingoid 
41 (44.1) 
5 (8.2) 
Erythema 
19 (20.4) 
3 (4.9) 
Hirsutism 
24 (25.8) 
1 (1.6) 
Weight increased 
21 (22.6) 
3 (4.9) 
Headache 
17 (18.3) 
12 (19.7) 
Nasopharyngitis 
21 (22.6) 
3 (4.9) 
Central obesity 
17 (18.3) 
2 (3.3) 
Increased appetite 
11 (11.8) 
1 (1.6) 
Pollakiuria 
12 (12.9) 
1 (1.6) 
Abdominal pain upper 
9 (9.7) 
4 (6.6) 
Upper respiratory tract infection 
10 (10.8) 
5 (8.2) 
Constipation 
7 (7.5) 
3 (4.9) 
Influenza 
4 (4.3) 
2 (3.3) 
Cough 
7 (7.5) 
3 (4.9) 
Abnormal behaviour 
7 (7.5) 
3 (4.9) 
Rash 
5 (5.4) 
3 (4.9) 
Skin striae 
4 (4.3) 
0 (0.0) 
Acne 
4 (4.3) 
1 (1.6) 
Nausea 
4 (4.3) 
2 (3.3) 
Vomiting 
2 (2.2) 
4 (6.6) 
Ear infection 
2 (2.2) 
1 (1.6) 
Diarrhoea 
4 (4.3) 
4 (6.6) 
Abasia 
0 (0.0) 
8 (13.1) 
Fall 
2 (2.2) 
1 (1.6) 
Appetite disorder 
0 (0.0) 
1 (1.6) 
Abbreviations: DMD, Duchenne muscular dystrophy; MedDRA, Medical Dictionary for Regulatory Activities; 
N, total number of individuals in a study; n, number of subjects; TEAE, treatment-emergent adverse events 
Note: Percentages are n/N*100. At each level of summarization, a subject is counted only once. MedDRA 
version 17.0 has been used for the coding of adverse events. 
Source: 120-Day Safety Update Table 18 (modified) 
Benefit/risk 
Study PTCEMF-GD-004 will evaluate the use of deflazacort in adult patients with LGMD2I. 
Deflazacort has been successively used to treat diseases not only in adults but also in vulnerable 
pediatric populations, including DMD, juvenile chronic arthritis, nephrotic syndrome, and bronchial 
asthma. The safety concerns related to deflazacort use are well known and can be managed through 
appropriate medical monitoring. Given the findings of case reports that suggest corticosteroid use 
may reduce disease progression in patients with LGMD2I, the potential benefits of the treatment 
outweigh the anticipated risks of the drug. 
Study assessments 
In this study, muscle function following deflazacort or placebo therapy will be evaluated using a 
number of tests that assessed different aspects of muscle function, such as peak physical activity 

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(timed-function tests), endurance (2-minute walk test), muscle strength (myometry), and pulmonary 
function (FVC, MIP, and MEP).  
The PK of deflazacort will be investigated to evaluate the exposure of the drug in subjects with 
LGMD2I; a population in which this assessment has not been previously performed. This information 
may help to determine the relationship of drug exposure with the efficacy and safety of the drug in 
this patient population. The following PK parameters will be calculated using noncompartmental 
analysis method: AUC(0-t), AUC(0-inf), Cmax, Tmax, CL/F, Vz/F, λz, and t½. 
Magnetic resonance imaging (specifically Dixon MRI and global T2) are noninvasive methods that 
will be used to measure changes in muscular fat fraction and water content, respectively, of the 
muscle following deflazacort treatment. These methods have been shown to detect therapeutic 
effects of corticosteroids in reducing inflammatory processes in skeletal muscle of boys with DMD 
(Arpan 2014, Hathout 2016a). The advantage of the use of these potential biomarkers is that they 
are anticipated to be independent of muscle function, such as the ability to walk (Hathout 2016a). 
The INQoL questionnaire, developed by Vincent et al. (2007), consists of 45 questions within 10 
sections, 4 sections focus on the impact of key muscle disease symptoms (weakness, locking [ie, 
myotonia], pain, and fatigue), 5 sections focus on the impact of muscle disease on particular areas of 
life (activities, independence, social relationships, emotions, and body image), and 1 section asks 
about the positive and negative effects of treatment, reflecting the trade-off between the positive 
and negative effects of treatment now and in the future (Vincent 2007). 
The life domains that emerged correspond to the broad domains believed to make up the QoL 
spectrum (physical, psychological, and social functioning). The questionnaire is structured to allow 
for variations in the individual characteristics that influence quality of life. 
Participants respond using a 7-point Likert scale.  
The final score is presented as a percentage of the maximum detrimental impact; therefore, a higher 
percentage indicates a greater impact and lower QoL. 
In the original study, INQoL was validated through 252 completed questionnaires, including adult 
patients with LGMD. More than 60% of all respondents reported an impact on the life areas 
included in the questionnaire. 
This scale has been used in LGMD studies (Peric 2018), where mental domains were less impaired 
than physical, and the presence of cardiomyopathy correlated with a worse QoL. 
This scale has been translated in several languages and validated for English in several countries. 
3.3 
Justification of Dose 
The subjects will receive a 0.6 mg/kg daily dose of deflazacort. This dose is lower than the 
recommended dose of 0.9 mg/kg/day for DMD. Based on the higher body weight of the subjects in 
this trial (age ≥18 years) compared with DMD patients, the lower dose of 0.6 mg/kg/day is justified 
in order to reduce tolerability issues and corresponds to the equivalent prednisone dose (0.5 
mg/kg/day) used in LGMD2I based on anecdotal reports. The study of Darin et al. found that initial 
treatment of prednisolone at doses ranging from 0.032 to 0.37 mg/kg/day improved symptoms of 
LGMD2I in 2 patients (Darin 2007). 
Nevertheless, the 0.9 mg/kg/day dose serves as benchmark for the following discussion. A clinical 
study in DMD subjects (N=24; age 4 to 16 years) (MP-104-CL-005) found administration of 

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deflazacort 0.9 mg/kg/day did not result in accumulation of 21-desDFZ after 7 days of oral dosing in 
children or adolescents; exposures to 21-desDFZ after oral administration of deflazacort to children 
and adolescents with DMD on Day 1 were similar to exposures measured on Day 8. The dose-
normalized exposure parameters and the dose-dependent parameters (clearance and volume of 
distribution) were consistent between children and adolescents. Multiple oral doses of deflazacort 
0.9 mg/kg/day were safe and well tolerated by children (ages 4 up to 12 years) and adolescent (ages 
12 to 16, inclusive) subjects with DMD. These results support the evaluation of the lower dose of 0.6 
mg/kg/day for this indication.  
Sufficient data exists for the safety of the proposed dosing in females and the study requires 
stringent contraceptive measures for both males and females in the absence of adequate 
reproductive toxicity studies. 
3.4 
Subject Transition Procedures: Version 3.0 to Version 4.0  
The sponsor will unblind the study and provide the principal investigator a listing of their subjects’ 
treatment assignments. Subjects enrolled (and randomized to study medication) under Protocol 
Version 3.0 will be transitioned to Version 4.0 according to the following procedure:  
Subjects Randomized to Placebo Prior 
to 01 February 2020  
Subjects will have the option to be consented under 
Version 4.0 and immediately accelerated to the Week 26 
visit and begin the open label study.  
Subjects Randomized to 
Deflazacort Prior to 01 February 2020  
Subjects will return to the clinic at their scheduled Week 26 
Visit under Version 3.0. At the Week 26 visit, the subject 
will undergo Week 26 procedures and have the option to 
re-consent under Protocol Version 4.0 and continue for an 
additional 26 weeks in the open label period. 
Subjects Randomized to Placebo 
AFTER 01 February 2020  
Subjects will have the option to be consented under 
Protocol Version 4.0 and begin at the Week 26 Visit (Open-
label period). 
Subjects Randomized to 
Deflazacort AFTER 01 February 2020  
Subjects will have the option to be consented under 
Protocol Version 4.0 at their Week 13 Visit. These subjects 
will be provided the option to re-consent to the study under 
Protocol Version 4.0 at Week 13 and continue until Week 
26. After Week 26, the subjects will be ineligible to continue 
for the additional 26 weeks of open label treatment. 
New subjects enrolled until 31 May 2020 Subjects will have the option to be consented under 
Protocol Version 4.0 and perform Baseline through Week 
26 visit procedures. These subjects will be assigned 
deflazacort in an open-label fashion. After Week 26, the 
subjects will be ineligible for the additional 26 weeks of the 
trial.  
Subjects may continue to be screened under Protocol Version 4.0 procedures  until the close of 
screening on May 31, 2020.  
3.5 
Study Completion 
The study will end when the last subject completes the follow-up visit. 

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4 
STUDY POPULATION 
The target population for this study is subjects, ≥18 years of age with LGMD2I.  
4.1 
Overview 
4.2 
Inclusion Criteria 
1. 
Genetic diagnosis of LGMD2I (confirmed mutation in the FKRP gene) 
2. 
Male and female subjects aged ≥18 years 
3. 
Ability to ascend 4 stairs ≥2.5 seconds and be able to complete the ascent and descent 
both at screening and baseline 
4. 
Ability to understand the nature of the study and the consent form and to comply with 
study related procedures 
5. 
Must weigh ≥35 to ≤112.5 kg 
4.3 
Exclusion Criteria 
1. 
Received ≥4 weeks of continuous, systemic corticosteroid therapy within 3 months of 
study the Screening Visit. 
2. 
Presence of significant cardiomyopathy as defined by echocardiogram (left ventricular 
ejection fraction <30%) at screening  
3. 
Requires fulltime ventilator support 
4. 
History of chronic systemic fungal or viral infections 
5. 
History of recent bacterial infection (including tuberculosis) per discretion of the 
Investigator 
6. 
Diagnosis of diabetes mellitus (controlled and/or uncontrolled) defined as HbA1c ≥6.5% 
(based on historical or present diagnosis) 
7. 
History of immunosuppression or other contraindications to glucocorticosteroid therapy 
8. 
Requires concomitant use or >1 week of drugs or substances that are moderate to strong 
CYP3A4 inhibitors (ie, clarithromycin, fluconazole, diltiazem, verapamil, grapefruit juice) 
or moderate or strong CYP3A4 inducers (ie, rifampin, efavirenz, carbamazepine, 
phenytoin) at baseline. 
9. 
Participated in an interventional clinical trial within the last 3 months prior to the 
baseline visit  
10. Unable or unwilling to comply with the contraceptive requirements of the protocol 
11. Female subjects who are pregnant and/or breastfeeding 

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12. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, 
gastrointestinal, cardiovascular, hepatic, neurologic, psychiatric, or allergic disease 
4.4 
Screen Failures 
Any subject that does not meet inclusion or exclusion criteria within the defined screening window 
prior to randomization, will be considered a screen failure. Screen failures can be rescreened after 
consultation with the Medical Monitor.  
5 
ENROLLMENT PROCEDURES 
5.1 
Source and Number of Subjects 
Approximately 30 subjects will be enrolled. Subjects will be recruited via existing LGMD2I 
populations at investigative sites and/or referrals.  
5.2 
Screening 
The Investigator must inform each study subject of the nature of the study, explain the potential 
risks, and obtain written informed consent from the legal guardian and/or study candidate (as 
required by local regulations) prior to performing any study-related screening procedures. 
6 
INVESTIGATIONAL PRODUCT(S)  
6.1 
Investigational Product(s) Administration 
The investigational medicinal to be used in this study is oral deflazacort, 0.6 mg/kg/day. 
6.1.1 
Investigational Product Description 
6.1.1.1 
Deflazacort 
Deflazacort will be provided as 6 mg, 18 mg, or 36 mg tablets for oral administration once daily. The 
drug substance and drug product are manufactured under current good manufacturing practice 
conditions. 
Each tablet contains deflazacort and the following inactive ingredients: colloidal silicon dioxide, 
lactose monohydrate, magnesium stearate, and pre-gelatinized corn starch.  
6.1.2 
Dosing and Administration 
Deflazacort will be assigned via an IRT system according to the subject’s weight at baseline. Subjects 
will be assigned deflazacort 0.6 mg/kg/day and will continue on the assigned weight based dose 
through 26 weeks. Any subject assigned to placebo prior to the Version 4.0 amendment will be 
switched to deflazacort as described above.  
Study drug will be taken by the subject orally, at home (except on days where the subject is 
instructed to take the dose in clinic), in a single, daily, morning dose. If the subject is unable to 
swallow the tablet whole, tablets may be crushed in between two spoons or using a tablet crusher 

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and stirred into soft food (eg, applesauce, pudding) and ingested immediately. Subject must be 
instructed not to split the tablet(s) and subjects are instructed not to chew the study drug. Tablets 
may be taken with or without water and with or without food.  
6.1.2.1 
Weight Bands 
Study participants will be assigned the appropriate, weight-based dosing band (excursions 
from the target weight permitted out to approximately 20%, greater or less, than target based 
on available tablet strengths) (Table 2): 
Table 2. 
Weight-based Dosing Summary 
0.6 mg/kg/day 
Dose (mg) 
Target Weight (in Kg) 
Weight Band (in Kg) 
Dosing Combination 
24 
40.0 
35 - 49.9 
6mg + 18mg 
36 
60.0 
50 -74.9 
36 mg 
54 
90.0 
75 - 112.5 
36mg + 18mg 
6.1.2.2 
Safety Criteria for Adjustment or Stopping Dosing 
Unless an occurrence of an AE requires otherwise, the investigator is encouraged to maintain the 
same dose through the first 13 weeks of treatment due to the potential to confound the PK, safety, 
and efficacy evaluations. Dose adjustments are permitted as follows: 
1. 
In order to maintain the weight-based dose of 0.6 mg/kg/day of deflazacort, if the 
subject has experienced weight gain that places them in the next higher weight band, the 
dose may be increased accordingly. If the subject has experienced an AE as described 
below, the Investigator may elect not to increase the dose despite weight gain. 
2. 
At the discretion of the Investigator, the dose may be decreased to that of the next lower 
weight band in response to an AE. See recommendations below. 
3. 
At the end of the study, subjects will switch from the study medication to an appropriate 
dose of a commercially available deflazacort or any other available corticosteroid. If the 
subject/Investigator does not wish to continue corticosteroid use, the dose of deflazacort 
must be reduced per Section 7.1 procedures. 
Discontinuation of deflazacort during Period 1 of the study should be avoided unless clinically 
necessary. In the case of the development of predictable, deflazacort-related adverse effects, 
appropriate supportive care should be provided such that dosage can be maintained. Specific, 
standard of care recommendations for precautionary interventions for specific 
corticosteroid-related AEs are given below. 
Acne 
In the event of bothersome acne that may be attributable to deflazacort, the following interventions 
are recommended:   
1. 
The subject should be encouraged to use appropriate conventional therapy for acne  

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2. 
If conventional therapy does not provide an adequate response, the dosage should not 
be increased to adjust for increases in body weight.  
3. 
If the acne is so severe that it cannot be managed with appropriate anti-acne measures, 
dosage reductions can be made down to the next lower weight band of the dosing arm 
assigned.  
Behavior Changes 
Where behavior changes are disruptive to family/school life, the following interventions are 
recommended: 
1. 
The subject should be encouraged to seek behavioral support from a qualified behavioral 
specialist. 
2. 
If the subject is already receiving behavioral advice under the guidance of a behavioral 
specialist, the dosage should not be increased to adjust for increases in body weight. 
Consideration can be given to administering the corticosteroid dose at night instead of in 
the morning. 
3. 
If there is no improvement despite behavioral advice under the guidance of a behavioral 
specialist, dosage reductions can be made down to the next lower weight band of the 
dosing arm assigned.  
4 
If the severe behavioral problems continue to cause unacceptable disruption to 
school/work/family life necessitating cessation of deflazacort, Section 7.1 procedures 
should be followed. 
Bone Fractures Due to Osteoporosis 
Subjects who experience limb fractures should have fixation as directed by an orthopedic surgeon. 
Subjects who develop vertebral fractures can be treated with bisphosphonates (eg, pamidronate, 
0.5 to 1 mg/kg/day intravenous for 3 days every 4 months). Subjects should not have a dosage 
adjustment due to the occurrence of fractures. 
Cataracts 
The development of cataracts should prompt referral to an ophthalmologist for evaluation. Subjects 
should not have a dosage adjustment due to the occurrence of cataracts.  
Cushingoid Appearance 
If the subject develops a Cushingoid appearance, that is unacceptable to the subject, the following 
actions are recommended: 
1. 
Reassurance and support should be provided. Counseling from a qualified behavioral 
specialist should be considered. 
2. 
If the Cushingoid appearance remains unacceptable to the subject, the dosage should 
not be increased to adjust for increases in body weight. 

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3. 
If the Cushingoid appearance remains unacceptable to the subject, a dose reduction can 
be made down to the next lower weight band of the dosing arm assigned.  
4. 
Every attempt should be made to avoid stopping deflazacort solely for Cushingoid 
appearance; however, should cushingoid appearance become unacceptable to the 
subject necessitating cessation of deflazacort, Section 7.1 procedures should be followed 
Gastrointestinal Irritation 
In the event of the development of symptoms consistent with esophagitis, gastritis, or duodenitis, 
the following interventions are recommended: 
1. 
Treatment with supportive care (H2 antagonists, proton pump inhibitors, antacids) 
should be initiated and dosage should not be increased to adjust for increases in body 
weight. 
2. 
If symptoms persist for ≥6 weeks despite supportive care (H2 antagonists, proton pump 
inhibitors, antacids), a gastroenterology consultation should be encouraged.  
3. 
If symptoms persist despite continued supportive care (H2 antagonists, proton pump 
inhibitors, antacids) and gastroenterology evaluation, dose reduction can be made down 
to the next lower weight band of the dosing arm assigned.  
4. 
If the gastroenterologist recommends discontinuation of deflazacort for frank 
gastrointestinal ulceration, bleeding, etc, Section 7.1 procedures should be followed. 
Hyperglycemia or Glycosuria 
Evidence of fasting hyperglycemia or ≥1+ glycosuria persisting for ≥6 weeks should prompt the 
following interventions: 
1. 
Monitor hemoglobin average blood sugar concentrations (A1c) to evaluate for evidence 
of chronic hyperglycemia. 
2. 
If hyperglycemia or glucosuria is only episodic and chronic hyperglycemia is not present 
by hemoglobin A1c, deflazacort should not be increased to adjust for increases in body 
weight.  
3. 
If chronic hyperglycemia is present by hemoglobin A1c, consultation should be arranged 
with an endocrinologist regarding diagnostic evaluation and potential intervention for 
hyperglycemia. 
4. 
If hyperglycemia persists and dose reduction is warranted, reduction can be made down 
to the next lower weight band of the dosing arm assigned. 
5. 
If the endocrinologist recommends deflazacort discontinuation, Section 7.1 procedures 
should be followed. 
Hypertension  

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Evidence of substantial hypertension (blood pressure elevation systolic BP ≥140 mmHg and or 
diastolic BP ≥90 mmHg) persisting for ≥6 weeks should prompt the following interventions: 
1. 
Dietary recommendations (weight reduction/sodium reduction) should be considered. 
2. 
Dosage should not be increased to adjust for increases in body weight. 
3. 
If substantial hypertension persists, appropriate blood pressure management 
(eg, diuretics, beta blockers, calcium channel blockers) can be considered.  
4. 
If hypertension persists despite continued antihypertensive therapy, dose reduction can 
be made down to the next lower weight band of the dosing arm assigned. 
5. 
If hypertension persists despite continued antihypertensive support and dosage 
reductions, Section 7.1 procedures should be followed. 
Infections Potentially Related to Corticosteroid-Mediated Immunosuppression 
Unusual opportunistic infections or unusual responses to infection potentially consistent with 
corticosteroid-mediated immunosuppression should prompt the following interventions: 
1. 
Consultation with an infectious disease expert should be obtained. 
2. 
If infections cannot be managed with appropriate antibiotic prophylaxis or treatment, 
dosage should not be increased to adjust for increases in body weight.  
3. 
If infections still cannot be managed with appropriate antibiotic prophylaxis or 
treatment, a dose reduction can be made down to the next lower weight band of the 
dosing arm assigned.  
4. 
If infections are clinically severe and/or persistent despite dosage reductions, Section 7.1 
procedures should be followed. 
Weight Gain 
In the event of a body weight increase that is unacceptable to the subject, the following 
interventions are recommended: 
1. 
Reassurance and support should be provided. Counseling from a nutritionist should be 
considered. 
2. 
Should weight increase continue to be unacceptable, dosage should not be increased to 
adjust for increases in body weight. 
3. 
If the body weight increase remains unacceptable to the subject, a dose reduction can be 
made down to the next lower weight band of the dosing arm assigned. 
4. 
Every attempt should be made to avoid stopping deflazacort solely for weight gain; 
however, if the subject demands that deflazacort be stopped, Section 7.1 procedures 
should be followed. 

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6.1.3 
Return of Study Drug 
Subjects should return all remaining/unused study drug to the study site at each onsite study visit. 
The Study Drug Administration Record (accountability log) will serve as the source document for 
drug supply to the subjects and will document the return of unused drug for compliance 
assessments. Unused study drug must be returned to PTC Therapeutics or its designee. Records 
documenting the date of study drug shipping, and amount shipped should be kept in the 
Investigator site study file. 
6.1.4 
Overdose or Inadvertent Exposure Precautions 
Treatment of acute overdose is based on clinical judgement, which may include immediate gastric 
lavage or emesis followed by supportive and symptomatic therapy. If non-study subjects (eg, sibling, 
parent) ingests the medication, a prompt call to the Medical Monitor is required to discuss 
appropriate care. 
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Acquisition and Accountability 
Drug will be supplied to the investigative site via courier from a depot. Sites will have an initial 
shipment sent prior to the first subject randomizing and resupplied automatically throughout the 
study. The Investigator must ensure that all study drug supplies are kept in a secure locked area with 
access limited to those authorized by the Investigator. The Investigator, through the IRT system, 
must maintain full accountability of the study drug from receipt to destruction. The IRT will maintain 
information such as the receipt of all study drug shipped by the Sponsor (or their representative), 
including but not limited to the date received, lot number(s), retest date(s), amount received, and 
the disposition of all study drug. Current dispensing records will also be maintained through the IRT 
system, including the date, amount, kit and lot(s) of study drug dispensed and the subject receiving 
the drug. 
6.2.2 
Formulation, Appearance, Packaging, and Labeling 
Deflazacort tablets (6 mg, 18 mg and 36 mg) will be used for this study. The tablets are white, and 
either round or ovular in shape depending on the strength of the tablet (6 mg and 18 mg tablets are 
round, 36 mg tablets are ovular). Tablets will be packaged in weekly blister cards. Weekly blister 
cards will be packaged into visit cartons. Tablets needed for appropriate taper dose will be available 
and packaged in bottles. The blister cards, visit cartons, and bottles will be labeled in accordance 
with participating country regulatory requirements and certified language text translation.  
6.2.3 
Storage and Stability 
Deflazacort should be stored at controlled room temperature. Detailed storage requirements should 
be as described in country-specific prescribing information. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
Study medication will be administered in an open-label fashion. 

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6.4 
Study Intervention and Compliance 
Subjects will receive properly labeled blister cards with the daily dose assignment broken out by 
week. Each subject will be instructed to take all tablets on a daily basis that correspond to the day of 
the week. Dosing should begin corresponding to the day of the week Visit 1 took place (eg, if Visit 1 
occurs on a Wednesday, the subject should be instructed to begin treatment by administering 
tablets from the blister card column associated with Wednesday). On the initial pack, the subject 
should not take tablets from preceding days of the week (eg, in the previous example, Sunday, 
Monday, Tuesday). These would be returned as unused supplies at the following visit. Study drug 
will be administered at home with the exception of Visit 1 and Visit 2 where the dose will be taken 
after the pre-dose PK sample has been collected (Visit 1 and Visit 2). Subjects must return empty 
blister cards and unused supplies at each study visit and in the event of an early termination for 
compliance assessments. 
Home dosing will be monitored via review of returned study medication packaging and subject 
interview. 
6.5 
Concomitant Therapy 
All medications taken by subjects 30 days prior to the first dose of study drug and through the 
follow-up visit will be recorded.  
All medications (prescription and over the counter), vitamin and mineral supplements, and herbs 
taken during the study will be documented on the concomitant medication electronic case report 
form (eCRF). Information recorded will include: start and stop dates, dose and route of 
administration, and indication.  
The Investigator is encouraged to consult the PTC medical monitor or designee with questions 
relating to specific drugs and their potential for interactions with deflazacort. 
6.5.1 
Rescue Medication 
There is no defined rescue medication for this study. Medication prescribed to mitigate the known 
adverse effects of deflazacort are not considered rescue medications. 
6.5.2 
Prohibited Medications 
Subjects receiving corticosteroids, including deflazacort, and concomitant therapy with 
neuromuscular blocking drugs (eg, pancuronium) may be at increased risk of developing an acute 
myopathy . 
Subjects should not receive live or attenuated vaccines during the study. 
Additionally, the continuous, concomitant use of strong CYP3A4 inhibitors and inducers are 
prohibited during the study (Table 3 and Table 4). If the use of any of the medications listed below 
(or another, unlisted CYP3A inhibitor/inducer) becomes medically necessary, the PI must discuss 
management and further study eligibility with the medical monitor. 

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Table 3. 
CYP3A Inhibitors 
Strong Inhibitors  
≥5-fold increase in AUC  
or >80% decrease in CL/F 
Moderate inhibitors   
≥2 but <5-fold increase in AUC 
or 50-80% decrease in CL/F 
Weak inhibitors   
≥1.25 but <2-fold increase in 
AUC or 20-50% decrease in 
CL/F 
boceprevir 
cobicstat 
clarithromycin 
conivaptan 
danoprevir/ritonavir 
diltiazem 
elvitegravir/ritonavir 
grapefruit juice 
idelalisib 
indinavir/ritonavir 
itraconazole ketoconazole  
lopinavir/ritonavir 
nefazodone 
nelfinavir 
paritaprevir/ritonavir/ombitasvir 
posaconazole 
ritonavir  
saquinavir/ritonavir  
telaprevir 
tipranavir/ritonavir 
troleandomycin 
voriconazole 
aprepitant 
cimetidine 
ciprofloxacin 
clotrimazole 
crizotinib 
cyclosporine 
dronedarone 
erythromycin 
fluconazole 
fluvoxamine 
imatinib 
tofisopam 
verapamil 
chlorzoxazone 
cilostazol 
fosaprepitant 
istradefylline 
ivacaftor 
lomitapide 
ranitidine 
ranolazine 
tacrolimus 
ticagrelor 
Abbreviations: AUC, area under the concentration-time curve; CL/F, clearance. 
Table 4. 
CYP3A Inducers 
Strong Inducers 
≥80% decrease in AUC 
Moderate Inducers 
50-80% decrease in AUC 
Weak Inducers 
20-50% decrease in AUC 
carbamazepine enzalutamide 
mitotane 
phenytoin 
rifampin 
St. John’s wort 
bosentan 
efavirenz 
etravirine 
modafinil 
armodafinil 
rufinamide 
Abbreviations: AUC, area under the concentration-time curve 
 

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7 
INVESTIGATIONAL PRODUCT DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Medication 
If the subject is discontinued from the study medication, the following 3 options are available: 1) 
taper off deflazacort; 2) in conversation with their healthcare provider, they could switch to a 
commercially available generic version of deflazacort; or 3) in conversation with their healthcare 
provider, they could switch to other commercially available corticosteroids. 
Long term administration of deflazacort may lead to suppression of the hypothalamicpituitary-
adrenal (HPA) axis. Rapid reduction or abrupt withdrawal of therapy that has been prolonged or at 
high doses can cause secondary adrenal insufficiency (suppression of the HPA axis), and steroid 
withdrawal or deprivation syndrome. Recovery from suppression of the HPA axis after discontinuing 
deflazacort can be prolonged (possibly 6 to 12 months) and may vary based on doses, dosing 
schedules and duration of deflazacort therapy. Since there is a great deal of individual variability in 
susceptibility to suppression of the HPA axis after chronic use of exogenous corticosteroids, it is not 
possible to predict with confidence which subjects will be affected. Deflazacort should not be 
stopped suddenly. Therefore, general tapering recommendations are provided; however, 
investigators may taper according to their standard of care and clinical judgement. If there is no 
standard tapering practice at the site, the following taper practice based on the PJ Nicholhof 
Protocol (Kinnett 2017) is advised (Table 5): 
1. 
Using the 6 mg tablet strengths from the available taper bottle, begin by giving a 20% to 
25% lower dose for two weeks 
2. 
Repeat step 1 and continue to lower the dose by 20% to 25% original dose until near 
physiologic dose (~0.1 mg/kg) 
3. 
If necessary, substitute deflazacort with short acting form of a corticosteroid 
(ie, hydrocortisone (0.3 mg/kg/day) 
4. 
Stop corticosteroids and observe for signs of adrenal crisis 
Table 5. 
Taper paradigm per weight band 
Weight 
Band 
(mg) 
0.6 mg/kg 
Target 
Weight 
1st Reduction 
*(~.45 mg/kg) 
2nd Reduction 
*(~0.3 mg/kg) 
3rd Reduction 
*(~0.15 mg/kg) 
Consider Short 
Acting 
Corticosteroid 
24 
40 kg 
18 mg 
12 mg 
6 mg 
Stop Deflazacort 
36 
60 kg 
30 mg 
18 mg 
12 mg 
Stop Deflazacort 
54 
90 kg 
42 mg  
30 mg  
18 mg 
Stop Deflazacort 
*Approximate mg/kg calculations based on the weight requirement to achieve exactly 0.6 mg/kg dose. 20% 
fluctuation (higher and lower weight) is inherent in each weight band and should be considered when applying 
the tapering paradigm. 

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7.2 
Participant Discontinuation/Withdrawal from the Study 
If it is determined by the Investigator that any subject will discontinue the study, all early 
termination visit procedures should be completed and the final visit should be captured as early 
termination (ET) in an electronic case report form. If it is determined that a subject will discontinue 
the study in between visits, the subject should return at earliest convenience for an early 
termination visit, following completion of any required study medication assessments. The PTC 
medical monitor should be informed via e-mail of when a subject discontinues study treatment. For 
subjects who terminated early/discontinued from the study and are tapering off deflazacort, a 
follow-up visit will occur approximately 4 weeks after the final study drug dose. In case of 
discontinuation due to an AE, the AE should be followed up by the investigator until it is resolved, or 
the investigator assesses it as chronic or stable. 
Reasons for discontinuation may be for any of the following reasons: 
1. 
The subject requests to be discontinued from the study 
2. 
The occurrence of a clinically significant worsening of disease status or change in a 
laboratory parameter that may place the subject at risk 
3. 
Upon consultation with the PTC Therapeutics medical monitor, the Investigator may 
withdraw the subject from deflazacort treatment, if, in the Investigator’s clinical 
judgment, it is not in the subject’s best interest to continue. 
4. 
The occurrence of a serious AE 
5. 
The occurrence of a protocol violation, if it interferes with the safety of a subject or data 
integrity 
6. 
The Sponsor or Investigator terminates the study 
7.3 
Lost to Follow-up 
Subjects are considered lost to follow-up if the subject does not return to the clinic and attempts to 
contact the subject were unsuccessful. Efforts must be made on the part of the site to avoid any 
subject being lost to follow-up during the study. Before subjects are considered lost to follow-up, a 
minimum of 2 documented telephone contact attempts and 1 certified letter within 6 weeks of the 
most recent planned study visit must be sent in efforts to contact the subject. After being 
considered lost to follow-up, a subject’s status may be changed if the subject makes contact at a 
later time provided the trial is ongoing. 
8 
STUDY ASSESSMENT AND PROCEDURES 
8.1 
Schedule of Events and Study Procedures 
Table 6 summarizes schedule of study procedures and assessments. 

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Table 6. 
Schedule of Events 
Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
A signed and dated informed consent 
must be obtained before conducting any 
study procedures. 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
Medical/Surgical 
History 
X 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
FKRP Genotyping 
X 
 
 
 
 
 
 
 
 
Samples will be collected for sequencing 
of the FKRP gene to confirm the 
presence of a mutation. Genetic testing 
for FKRP will not be performed if 
documentation of genetic diagnosis is 
available at screening. 
Enrollment 
 
X 
 
 
 
 
 
 
 
The site will conduct initial subject 
registration in the IRT system at 
Screening. At Visit 1 (baseline), eligible 
subjects will be assigned dose via the 
IRT system. 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
 
X 
X 
 
X 
X 
 
 
Clinical Labs 
(Hematology6 and 
Chemistry7) 
X 
X 
 
X 
X 
 
X 
X 
 
Fasting approximately 8 hours prior to 
assessments. 
Pregnancy Test8 
X 
X 
 
X 
X 
 
X 
X 
 
All urine pregnancy tests taken at site 
will be confirmed by serum HCG. The 
urine pregnancy test must be negative 
prior to dispensation of study drug. 
Height/Weight/BMI 
X 
X 
 
X 
X 
 
X 
X 
 
For study inclusion, weight range must 
be ≥35 to ≤112.5 kg 
Vitals (HR & BP) 
X 
X 
 
X 
X 
 
X 
X 
 
 
ECG 
X 
 
 
X 
X 
 
 
X 
 
 

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Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
Echocardiogram 
X 
 
 
 
 
 
 
 
 
Echocardiograms obtained within 3 
months of enrollment are sufficient to 
obviate the screening echocardiogram. 
AE/SAE 
monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications information 
will need to be collected starting 30 days 
prior to first dose of study drug. 
Ophthalmic Exam9 
 
X 
 
 
X 
 
 
X 
 
Ophthalmic exams may be scheduled 
within 45 days of scheduled visit to 
accommodate scheduling restrictions. 
Lateral Spine 
X-ray10 
 
X 
 
 
X 
 
 
X 
 
 
DEXA10 
 
X 
 
 
X 
 
 
X 
 
 
Columbia Suicide 
Rating Scale 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Blood 
Sampling11 
 
X 
 
X 
 
 
 
 
 
PK samples will be drawn at Visit 1 and 
Visit 2 (steady state) for pharmacokinetic 
evaluation. The following PK parameters 
if possible, will be calculated using 
noncompartmental analysis method: 
AUC(0-t), AUC(0-inf), Cmax, Tmax, CL/F, 
Vz/F, λz, and t½,. Samples will be drawn 
at pre-dose, and 0.5, 1, 2, 4, and 6 
hours post-dose at baseline and Week 
13 visits. 
 
 
 
 
 
 
 
 
 
 
 
Timed Function 
Tests12 
X 
X 
 
X 
X 
 
X 
X 
 
Timed function tests will be recorded 
and assessed centrally in addition to the 
site’s clinical evaluator’s assessment at 
the visit. Timed function tests include 
time to up and go, time to descend 4 
stairs, time to climb 4 stairs, time to 
run/walk 10 meters, and 2-minute walk 

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Study Procedure Screening1 
Visit 
1
2 
Safety 
Call 
Visit 2 
Visit 3
3 
Safety 
Call 
Visit 4 
Visit 
5/ET4 
Follow-
up5 
NOTES 
Week 
(visit window) 
-6 to -1 
Weeks 
Baseline
/ Week 1 
Week 3 
(±1 weeks) 
Week 13 
(±2 weeks)
Week 26 
(±2 weeks)
Week 28 
(±2 weeks)
Week 39 
(±2 weeks)
Week 52 
(±2 weeks)
 
 
test. Conduct details will be summarized 
in a manual separate from this protocol. 
Hand Held 
Myometry12 
 
X 
 
X 
X 
 
X 
X 
 
 
Pulmonary 
Function Testing12 
 
X 
 
 
X 
 
X 
X 
 
Pulmonary function will be evaluated by 
spirometry. Pulmonary function test 
procedures will be detailed in a manual 
separate from this protocol. The 
following pulmonary function tests will be 
evaluated: FVC, MIP, and MEP.  
Biomarker testing 
(Bone Health 
Assays)13 
 
X 
 
X 
X 
 
 
X 
 
 
INQoL 
Questionnaire14 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI12,15 
 
X 
 
X 
X 
 
 
X 
 
Dixon MRI and T2 MRI will evaluate 
muscular fat fraction and inflammation, 
respectively, of selected lower limb 
muscles. Details will be further 
elucidated in an MRI manual separate 
from this protocol. 
Study Drug 
Administration 
 
 
 
 
 
 
 
 
 
 
Dispense Drug 
via IRT 
 
X 
 
X 
X 
 
X 
 
 
 
Unused Drug 
Return/ 
Compliance 
 
 
 
X 
X 
 
X 
X 
X5 
 
Abbreviations: AE, adverse event; BP, blood pressure; BMI, body mass index; DEXA; dual-energy X-ray absorptiometry; ECG, electrocardiogram; ET, early 
termination; FKRP, fukutin-related protein gene; FVC, forced vital capacity; HCG; human chorionic gonadotropin; HR, heart rate; INQoL, Individualized 
Neuromuscular Quality of Life; IRT, Interactive Response Technology; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MRI, magnetic 
resonance imaging; PD, pharmacodynamic; PK, pharmacokinetic; SAE, serious adverse event 
Note: See also Section 3.4 for explanation of the transition from Protocol Version 3.0 to Version 4.0. 
1 
Screening procedures must take place within 42 days of baseline visit (Visit 1). No study-related procedures should be performed prior to the signature of the 

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informed consent document(s). 
2 
Any screening procedure completed within and including 7 days of Visit 1, with the exception of the time to climb 4 stairs, can serve as baseline and does not 
need to be repeated at Visit 1. The time to climb 4 stairs must always be performed twice at the baseline visit and all other visits. The second 4 stair climb 
test should be done a minimum of 5 minutes after the prior test, or any other physical activity. The baseline visit may be split into two consecutive days. 
3 
At Visit 3, subjects initially randomized to deflazacort will continue deflazacort treatment while subjects originally randomized to placebo will initiate 
deflazacort treatment at a target dose of 0.6 mg/kg/day. For placebo subjects, all assessments will be performed prior to first dose of deflazacort (See also 
Section 3.4 for explanation of the transition from Protocol Version 3.0 to Version 4.0).  
4 
At Visit 5/ET, subjects/Investigators who elect to discontinue corticosteroid therapy altogether will need to taper off deflazacort. If it is determined by the 
Investigator that any subject will discontinue the study, all early termination visit procedures should be completed and the final visit should be captured as 
early termination (ET) in an electronic case report form (eCRF). If it is determined that a subject will discontinue the study in between visits, the subject 
should return at earliest convenience for an early termination visit, following completion of any required study medication assessments. For subjects who 
terminated early/ discontinued from the study and are tapering off deflazacort, a follow-up visit will occur approximately 4 weeks after the final study drug 
dose. In case of discontinuation due to an AE, the AE should be followed up by the investigator until it is resolved, or the investigator assesses it as chronic 
or stable. 
5 
The follow-up visit will be a phone call approximately 4 weeks after Visit 5 for subjects that complete the study and immediately start receiving commercial 
deflazacort or another corticosteroid. The follow-up will be an office visit for subjects that are tapering off deflazacort to return study drug and for site 
collection of any AEs and will occur 4-weeks after last dose of study drug.  
6 
Hematology assessments include hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and mean 
corpuscular hemoglobin concentration, mean platelet volume, red blood cell distribution width, neutrophils (% and absolute), total lymphocytes (% and 
absolute), monocytes (% and absolute), eosinophils (% and absolute), basophils (% and absolute), and platelets. 
7 
Chemistry assessments include sodium, potassium, chloride, bicarbonate, blood urea nitrogen (urea), creatinine, uric acid, protein (total), albumin, bilirubin 
(total), aspartate transaminase, alanine transaminase, gamma glutamyl transpeptidase, alkaline phosphatase, lactase dehydrogenase, glucose (fasting), 
hemoglobin A1c, calcium, phosphate, magnesium, creatine kinase, cholesterol, high density lipoproteins, low density lipoproteins (calculated), and 
triglycerides. 
8 
Only for women of child-bearing potential. 
9 
Ophthalmological examination includes a glaucoma assessment, cataract assessment, and intraocular pressure measurement. 
10 If possible, both X-ray and DEXA should be performed; however, only an X-ray or DEXA is acceptable if the other technology is not available or prohibited 
per local ethical/regulatory decree. 
11 The pre-dose blood draw will be taken within 2 hours before dosing. For timepoints up to 2-hours post dose, a window of ± 10 minute will be allowed for blood 
collection. From 4 hours to 6 hours post samples, a window of ± 30 minutes will be allowed. 
12 Efficacy and PD assessments will be performed post-daily-dose at each clinic visit, except for the baseline visit (Visit 1). At screening and baseline visits, the 
ability to ascend 4 stairs must be ≥2.5 and ≤8 seconds. In addition, the 4-stair climb will be performed twice at each visit. The second test should be done a 
minimum of 5 minutes after the prior test (or any other physical activity). The two 4-stair climb results must be within 20% of one another. If they are not the 
Medical Monitor should be contacted. 
13 Biomarker testing (bone health assays) include bone alkaline phosphatase (BAP), Beta-CrossLaps (Beta-CTx), insulin-like growth factor-1 (IGF1), 
parathyroid hormone (PTH) intact, aldosterone, and vitamin D (Serum 25-hydroxyvitamin D3). 
14 INQoL will be performed before the first dose at baseline and after 26 weeks of treatment, when possible.  
15 Dixon MRI and T2 MRI will be conducted at a subset of sites that have been pre-qualified by a central imaging vendor to perform this assessment. To be pre-
qualified, a site must have access to whole-body scanner and appropriate personnel and must have been trained on the procedure for data acquisition. MRI 
data will be analyzed centrally. 

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8.2 
Efficacy Assessments 
For the efficacy assessments of pulmonary function, timed function tests, and hand held myometry, 
each site will have at least one and preferably two trained clinical evaluators who are qualified 
physical therapists and who will have undergone standardized training. They must be certified as 
capable of performing all clinical assessments as specified for this study. Their strength measures, 
results of lung function tests and timed function tests must match those of the trainer within set 
acceptability parameters that are detailed in the clinical evaluator manual. Other efforts to reduce 
variability, include making every effort to have each subject assessed by the same clinical evaluator 
for each type of assessment throughout the entire study. Assessments must be conducted in the 
same order at each visit as stated in the clinical evaluator manual and at approximately the same 
time of day throughout the study. Clinical evaluators will not have access to prior test results to 
avoid bias based on knowledge of previous data. 
Clinical assessments conducted by the physical therapists will be monitored for quality control by an 
expert team of physical therapists. Videos will be uploaded to a cloud based secure storage facility 
for centralized review. Clinical evaluator performance will be documented by a report which is sent 
to the evaluators and stored in the site files as well as within the secure cloud-based facility. 
Informed consent for video review will be obtained from the subject. 
8.3 
Pharmacokinetic Assessments 
Blood samples (at least 1 mL per sample) will be collected for determination of 21-desacetyl 
deflazacort and 6β-hydroxy-21-desacetyl deflazacort. Pharmacokinetic sample collection, 
processing, storage, and shipment will be performed according to instructions outlined in the PK 
laboratory manual separate from this protocol. 21-desacetyl deflazacort and 6β-hydroxy-21-
desacetyl deflazacort plasma concentrations will be determined by the bioanalytical group of 
Celerion, Lincoln, Nebraska, USA, using a validated liquid chromatography with tandem mass 
spectrometry (LC-MS/MS) method. The lower limit of quantification of the LC-MS/MS method for 
simultaneous determination of 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort is 
1.0 and 0.5 ng/mL respectively. 
The pre-dose blood draw will be taken within 2 hours before dosing. For timepoints up to 2-hours 
post dose, a window of ± 10 minutes will be allowed for blood collection. From 4 hours to 6 hours 
post samples, a window of ± 30 minutes will be allowed. 
8.4 
Adverse Events and Serious Adverse Events 
8.4.1 
Definition of an adverse events 
An adverse event is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not it is considered related to the drug. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease in a study subject 
who is administered study drug in this study. 

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For this protocol, untoward medical occurrences that should be reported as AEs include the 
following: 
1. 
All AEs during the course of treatment with study drug administration 
2. 
All AEs resulting from medication misuse, abuse, withdrawal, or overdose, of study drug 
3. 
All AEs resulting from medication errors such as dispensing or administration error 
outside of what is described in the protocol 
4. 
Apparently unrelated illnesses, including worsening of a preexisting illness 
5. 
Injury or accidents. Note that if a medical condition is known to have caused the injury or 
accident (a fall secondary to dizziness), the medical condition (dizziness) and the accident 
(fall) should be reported as 2 separate AEs. The outcome of the accident (hip fracture 
secondary to the fall) should be recorded in source documents. 
6. 
Abnormalities in physiological testing or physical examination findings that require 
clinical intervention or further investigation (beyond ordering a repeat [confirmatory] 
test) 
7. 
Laboratory or ECG abnormalities that require clinical intervention or further investigation 
(beyond ordering a repeat [confirmatory] test) unless they are associated with an already 
reported clinical event. Laboratory abnormalities associated with a clinical event should 
be captured in the source documents. Laboratory abnormalities not requiring clinical 
intervention or further investigation will be captured as part of overall laboratory 
monitoring and should not be reported as AEs. 
8. 
A preexisting condition (eg, allergic rhinitis) must be noted on the appropriate eCRF for 
Visit 1 but should not be reported as an AE unless the condition worsens, or episodes 
increase in frequency during the AE reporting period. Diagnostic and therapeutic 
noninvasive and invasive procedures, such as surgery, should not be reported as AEs. 
However, the medical condition for which the procedure was performed should be 
reported if it meets the definition of an AE. For example, an acute appendicitis that 
occurs during the treatment with study drug should be reported as the AE and the 
resulting appendectomy should be recorded in the source documents and eCRF. If a 
surgical procedure was planned prior to entry into the study, and the surgery is not 
performed because of a worsening of a baseline condition, this should not be reported as 
an AE. Note that, as described in Section 8.4.2 any hospitalization occurring as the 
consequence of an AE during the study period should be reported as an serious adverse 
event (SAE). 
Each AE is to be classified as serious or non-serious by the Investigator using medical and scientific 
judgment. 

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8.4.2 
Definition of a serious adverse events 
An SAE is an untoward medical occurrence or effect associated with the use of a study drug at any 
dose, regardless of whether it is considered by the Investigator to be related to the study drug, 
which results in one of the following: 
1. 
Results in death. This includes all deaths on treatment or within 30 days after last study 
drug administration, including deaths due to disease progression. Any death occurring 
later than 30 days following the last dose need not be reported as an SAE unless it is a 
result of an event that started within the period covered by the on-study definition. The 
reported AE should be the event that caused the death. In addition, any AE resulting in 
death that occurs subsequent to the AE reporting period and that the Investigator 
assesses as possibly related to the study drug should also be reported as serious. 
2. 
Is life-threatening. This refers to an event in which the subject was at risk of death at the 
time of the event. It does not include an event that, had it occurred in a more severe 
form, hypothetically might have caused death. 
3. 
Requires hospitalization or prolongation of existing hospitalization (excluding 
hospitalizations for administration of the study drug, procedures required by the study 
protocol, or treatment-related diagnostic procedures; other planned hospitalizations; or 
hospitalizations related only to progression of disease). Treatments in the emergency 
room for procedures such as hydration that do not require admitting the subject to the 
hospital and observational durations in the emergency room for less than 24 hours do 
not fall into this category. 
4. 
Results in persistent or significant disability or incapacity or substantial disruption of the 
ability to conduct normal life functions, not related to cancer. 
5. 
Any other medically important event that the Investigator or the sponsor judges to be 
serious or which is defined as serious by the regulatory agency in the local country. These 
are AEs that might not be immediately life-threatening or result in death or 
hospitalization but might jeopardize the subject or might require intervention to prevent 
one of the other outcomes listed above. Medical judgment should be exercised in 
deciding whether an AE is serious based on above definition. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
6. 
A pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or congenital 
anomaly (including that in an aborted fetus). 
Note that any SAEs occurring within 30 days after last study drug administration (end of 
study) should be reported to the sponsor if the Investigator becomes aware of them. 

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8.4.3 
Unexpected Adverse Events 
The Investigator Brochure contains the Reference Safety Information (RSI) which will be used for 
assessing expectedness. If an event is not listed in the RSI, it should be considered unexpected or if 
the AE occurs at a greater severity, specificity or frequency, it should be considered unexpected. 
8.4.4 
Eliciting adverse event information 
The Investigator is to report all directly observed AEs and all AEs spontaneously reported by the 
study subject. In addition, each study subject will be questioned about AEs at each scheduled clinic 
visit after study drug administration or during any telephone contact with the subject. The type of 
question asked should be open-ended, for example, “How have you been feeling?” or a similar type 
of query. 
8.4.5 
Recording Serious and Non‑serious Adverse Events  
All AEs (both serious and non-serious) that occur in subjects during the AE reporting period must be 
recorded, whether or not the event is considered drug related. In addition, any known untoward 
event that occurs subsequent to the AE reporting period that the Investigator assesses as possibly 
related to the investigational drug/product should also be recorded as an AE. 
All AEs are to be recorded in the source documents and on the eCRF using concise medical 
terminology; whenever possible, terms contained in the Medical Dictionary for Regulatory Activities 
(MedDRA) should be employed. In addition, the following information should be recorded: 
1. 
Indication of whether the event is serious or non-serious (see Section 8.4.2) 
2. 
Relationship to study drug (see Section 8.4.2) 
3. 
Severity of the event (see Section 8.4.7) 
4. 
Onset date 
5. 
Resolution date, or date of death 
6. 
Action taken 
7. 
Outcome of the event 
Classification of the event as serious or non-serious determines the reporting procedures to be 
followed. 
8.4.6 
Describing adverse event relationship to study drug 
The Investigator should provide an assessment of the relationship of the AE to the study drug, ie, 
whether there is a reasonable possibility that the study drug caused the AE, using the considerations 
outlined in Table 7. 

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Table 7. 
Relationship of Study Drug to Adverse Event Relationship 
Relationship 
Description  
Probable  
A clinical event in which a relationship to the study drug seems probable because 
of such factors as consistency with known effects of the drug; a clear temporal 
association with the use of the drug; improvement upon withdrawal of the drug; 
recurrence upon rechallenge with the drug; lack of alternative explanations for the 
event.  
Possible  
A clinical event occurring coincident with administration of the study drug and 
which may or may not be explained by concurrent disease or other drugs or 
chemicals. Information on drug withdrawal or rechallenge may be lacking.  
Unlikely  
A clinical event with a temporal relationship to the study drug exposure that does 
not preclude causality but for which there is a clear alternate cause that is more 
likely to have caused the adverse event than study drug. Such alternatives include 
a concomitantly administered drug, the subject’s disease state, other medical 
conditions, or environmental factors.  
Unrelated  
A clinical event, for which a relationship to the study drug seems improbable 
because of factors such as inconsistency with known effects of the study drug, lack 
of a temporal association with study drug administration, lack of association of the 
event with study drug withdrawal or rechallenge, and/or presence of alternative 
explanations for the event. Alternative explanations might include a known 
relationship of the adverse event to a concomitant drug, medical history of a similar 
event, the subject’s disease state, other medical conditions, or environmental 
factors.  
8.4.7 
Grading of Severity of Adverse Event 
The severity of AE will be graded using the Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0 (refer to the Study Manual). For each episode, the highest severity grade 
attained should be reported. 
If a CTCAE criterion does not exist, the Investigator should use the grade or adjectives: Grade 1 
(mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal) to 
describe the maximum intensity of the AE. For purposes of consistency with the CTCAE, these 
intensity grades are defined in Table 8. 
Table 8. 
Grading of Adverse Event Severity Grade 
 
Adjective  
Description  
Grade 1  
Mild  
Sign or symptom is present, but it is easily tolerated, is not expected 
to have a clinically significant effect on the subject’s overall health 
and well-being, does not interfere with the subject’s usual function, 
and is not likely to require medical attention  
Grade 2  
Moderate  
Sign or symptom causes interference with usual activity or affects 
clinical status, and may require medical intervention  
Grade 3  
Severe  
Sign or symptom is incapacitating or significantly affects clinical 
status and likely requires medical intervention and/or close follow-up  
Grade 4  
Life-threatening Sign or symptom results in a potential threat to life  
Grade 5  
Fatal  
Sign or symptom results in death  

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8.4.8 
Adverse Event Reporting 
Investigator site reporting requirements for AEs are summarized in Table 9. 
Table 9. 
Investigator Site Requirements for Reporting Adverse Events 
Event 
Recorded on the eCRF 
Reported on the SAE Report Form to 
PTC Pharmacovigilance Within 24 
Hours of Awareness   
Serious AE 
All  
All  
Non-Serious AE 
All  
None  
Exposure to the study drug 
during pregnancy or 
breastfeeding, and 
occupational exposure 
All (regardless of 
whether associated with 
an AE), except 
occupational exposure 
Exposure during pregnancy, exposure 
via breastfeeding, occupational exposure 
(regardless of whether associated with 
an AE) 
Abbreviations:  AE, adverse event; eCRF, electronic case report form; SAE, serious adverse event 
All AEs should be followed up by the Investigator until they are resolved, or the Investigator assesses 
them as chronic or stable. The Investigator should consider protocol guidelines and use his/her 
discretion in ordering additional tests as necessary to monitor the resolution of such events. In the 
event of additional investigations, the PTC Therapeutics Pharmacovigilance Department or designee 
should be informed via e-mail or fax. A subject withdrawn from the study because of an AE must be 
followed by the Investigator until clinical recovery is complete and laboratory results have returned 
to normal, or until progression has been stabilized. Follow-up may need to continue after the 
subject has discontinued from the study, and additional investigations may be requested by the PTC 
Therapeutics medical monitoring team. 
The first day of AE reporting will coincide with the date of signing of informed consent and including 
a minimum of 30 calendar days after the last administration of study drug. 
8.4.9 
Serious Adverse Event Reporting 
All SAEs should be reported via the SAE report form to PTC Therapeutics within 24 hours of 
becoming aware of the event(s). In addition, the AE portion of the eCRF must also be completed. 
The SAE report form should be signed by the Investigator; however, if the Investigator is unable to 
sign at the time of the event or within 24 hours, the form should be signed by the clinical staff 
member reporting the SAE (eg, the study coordinator). The SAE report form must be faxed or e-
mailed to the PTC Therapeutics Pharmacovigilance Department or designee and to the site 
Institutional Review Board/Institutional Ethics Committee (IRB/IEC) (if required by local regulations) 
within 24 hours. 
Follow-up information to the SAE should be clearly documented as “follow-up” in the SAE report 
form and must also be faxed or e-mailed to the same party. All follow-up SAE report forms for the 
event must be signed by the Investigator. Any source documents (eg, progress notes, nurses’ notes, 
laboratory and diagnostic test results, discharge summaries) provided to the sponsor should be 
redacted so that the subject’s name, address, and other personal identity information are obscured. 
Only the subject’s study number and initials are to be provided (in regions where the provision of 
such information is permitted). The information in the AE portion of the eCRF and the SAE report 
form(s) must match or be reconciled. Where the same data are collected, the forms must be 
completed in a consistent manner. For example, the same AE term should be used on both forms. 

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In the rare event that the Investigator does not become aware of the occurrence of an SAE 
immediately (for example, if a subject initially seeks treatment elsewhere), the Investigator is to 
report the event within 24 hours after learning of it and to document his/her first awareness of the 
AE. 
The PTC Therapeutics Pharmacovigilance Department contact information for reporting SAEs is 
provided below. This information is also provided in the Study Manual and in the SAE report form. 
PTC Therapeutics Safety Department 
Attention: Pharmacovigilance 
E-mail:
Facsimile:
8.4.10 
Contraception 
Women of child bearing potential (WOCBP) includes any female who has experienced menarche and 
who has not undergone successful surgical sterilization (eg, hysterectomy, bilateral tubal ligation, 
bilateral oophorectomy) or is not postmenopausal. Postmenopausal is defined as ≥12 months with 
no menses without an alternative medical cause. Women who are WOCBP and are using an active 
method of birth control, are practicing abstinence or where the partner is sterile (eg, vasectomy), 
are considered to be WOCBP. 
WOCBP must use 2 forms of effective contraception simultaneously for the duration of study 
participation in a manner such that risk of failure is minimized. Periodic and/or temporary 
abstinence such as declaration of abstinence during study participation or fertility awareness-based 
methods to prevent pregnancy (including but not limited to symptothermal and ovulation 
estimation by either calendar day or salivary/cervical secretions) are not considered effective 
methods of birth control; however, true (absolute) sexual abstinence (ie, in line with the preferred 
and usual lifestyle of the subject) may be permitted. Effective methods of birth control approved for 
use in this study are: 
1. 
Implants (eg, Norplant® system) 
2. 
Injectable (eg, Depo-Provera®) 
3. 
Transdermal patch 
4. 
Combined oral contraceptives 
5. 
Barrier methods (condoms and diaphragm with spermicide) – note: double barrier 
method is required if no other methods of birth control are in use 
6. 
Intrauterine devices (eg, ParaGard®, Mirena®) 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding pregnancy during 
trial participation. During the trial, all WOCBP will be instructed to contact the Investigator 
immediately if they suspect they might be pregnant (eg, missed or late menstrual period). 

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8.4.11 
Reporting Pregnancy 
PTC Therapeutics should be notified in the event that a female subject in the study, or a female 
partner of a male subject in the study, becomes pregnant on-study or within 30 days of the last 
administration of study drug must be reported on a Pregnancy Notification Form (see Study Manual 
for details). 
This must be done whether or not an AE has occurred and within 24 hours of awareness of the 
pregnancy. The information submitted should include the anticipated date of birth or pregnancy 
termination. 
Written consent is required prior to collecting and reporting any information on a female partner of 
a male subject in the study. 
If possible, the Investigator should follow the subject, or the pregnant female partner of a male 
subject, until completion of the pregnancy and notify the PTC Therapeutics medical monitor of the 
outcome within 5 days or as specified below. The Investigator will provide this information as a 
follow-up to the initial Pregnancy Notification Form via the Pregnancy Outcome Form (see the Study 
Manual for details). 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(ie, spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus]), the Investigator should follow the procedures for reporting SAEs, ie, report the 
event to the PTC Therapeutics Safety Department or designee and follow-up by submission of 
appropriate AE eCRFs (see Section 8.4.9). 
8.4.12 
PTC Therapeutics Adverse Event Reporting Requirement 
As the sponsor of the study, PTC Therapeutics is responsible for reporting certain safety information, 
particularly SAEs and subject deaths related to participation in the study, to each investigator in an 
expedited manner. If notification of an AE requiring expedited reporting to investigators is received, 
PTC Therapeutics or its designated representative will contact each investigational site participating 
in this study by e-mail, fax, and/or overnight mail such that the Investigator can promptly notify the 
site IRB/IEC per their local requirements. The initial expedited safety report will be provided as 
required according to local regulations (eg, within 15 days) after the earliest date PTC Therapeutics 
or an agent of PTC Therapeutics (eg, a site monitor) becomes aware of an AE. This awareness date is 
the date the regulatory reporting clock begins, and the date is considered Day 0. 
8.4.13 
Safety Monitoring 
Subjects will be monitored closely for adverse events or laboratory abnormalities, or other safety 
assessments (ie, height, weight, vital signs, electrocardiograms, and physical examination) during 
the course of the study. 
For adverse events or laboratory abnormalities, the Investigator should use his/her judgment in 
determining whether the event or abnormality is clinically significant, whether diagnostic evaluation 
is warranted, and whether potential interruption of study drug therapy is appropriate. 

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While specific monitoring, diagnostic testing, and supportive care measures must be instituted 
based on the clinical judgment of the Investigator, investigators are encouraged to contact the 
medical monitor to obtain guidance and to ascertain whether similar events are being seen at other 
sites. The medical monitor should be notified of any adverse event or laboratory abnormality that 
leads to dose interruption and should be apprised of ancillary laboratory or other diagnostic findings 
and the evolving data from any work-up of the initial abnormality. The medical monitor may suggest 
review of the case with gastroenterology, endocrinology, nephrology consultants or with other 
experts (either at the site or retained by PTC Therapeutics). 
9 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypothesis 
No hypothesis will be tested in this study.  
9.2 
Sample Size Determination 
This is a single arm, open label study to evaluate the efficacy and safety of deflazacort in subjects 
with LGMD2I. The primary endpoint is the change in 4-stair climb in seconds after 26 weeks of 
treatment. Summary statistics such as mean, standard deviation, median, minimum and maximum 
will be provided for the change in 4-stair climb in seconds after 26 weeks of treatment. The 95% 
confidence interval for the mean will be provided as well. 
If assuming the deflazacort can prevent subjects’ further progression within 6 months i.e. the mean 
change of 4-stair climb after 26 weeks of treatment is Zero second and the standard deviation of the 
change is 0.7, with a total of 30 subjects, the 95% confidence will be from -0.25 to 0.25 seconds.  
9.3 
Population for Analyses 
9.3.1 
Full/Safety Population 
The Full/Safety population includes all enrolled subjects who receive at least one dose of 
deflazacort. 
9.3.2 
Pharmacokinetic Population 
The pharmacokinetic population includes all enrolled subjects who received at least 1 dose of study 
drug and had sufficient concentration-time data for the calculation of PK parameters. 
9.4 
General Statistical Considerations 
Continuous variables will be summarized using the number of non-missing observations (N), mean, 
standard deviation, minimum, median, and maximum. Categorical variables will be summarized 
using count and percentage.  
By-patient listings will be created for each case report form (CRF) module. 

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9.5 
Specific Statistical Analyses 
9.5.1 
Study Conduct  
All protocol deviations will be listed and summarized. 
9.5.2 
Subject Disposition 
The disposition of subjects will be summarized, including the number of subjects screened, the 
number of screen failures, the reason of screening failure, the number of subjects enrolled, the 
number of enrolled subjects who received at least 1 dose of study drug. The number of subjects who 
prematurely discontinued study drug and the discontinuation reason will be tabulated. 
9.5.3 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics of subjects will be summarized descriptively based on 
Full/Safety Population. 
9.5.4 
Study Treatment and Extent of Exposure 
All analyses of treatment exposure will be conducted using the safety population. Duration of 
treatment exposure, and treatment compliance, will be summarized by actual treatment received in 
the safety population. The dose modifications and modification reasons will be listed and 
summarized as well. 
9.5.5 
Prior and Concomitant Medication  
Prior and concomitant medications will be coded using the version of World Health Organization 
Drug Dictionary currently in effect into Anatomical-Therapeutic-Chemical classification codes. The 
types and the dates of concomitant medications will be listed and summarized. 
9.5.6 
Analyses of Primary Endpoints 
The primary efficacy endpoint (change in 4-stair climb in seconds) will be summarized the number of 
non-missing observations (N), mean, standard deviation, minimum, median, and maximum. The 95% 
confidence interval for the mean change after 26 weeks of treatment will be provided as well. 
Analyses of Secondary Endpoints for Efficacy 
Similar as the primary endpoint, summary statistics such as n, mean, standard deviation, median, 
minimum and maximum, and the 95% confidence interval for the mean change will be provided for 
all secondary endpoints. 
9.5.7 
Analyses of Secondary Endpoints for Safety 
Safety results will be summarized in safety population. 
The baseline value is defined as the last non-missing value prior to the first dose. 

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9.5.7.1 
Adverse Events 
Adverse events will be classified as pre-treatment adverse event, treatment-emergent adverse 
event (TEAE) and post-treatment adverse event. Pre-treatment AE is defined as the AE occurring or 
worsening prior to the start of the study treatment. TEAE is defined as the AE occurring or 
worsening on or after the first study dose and up to 30 days after the last study dose. Post-
treatment AE is defined as the AE occurring or worsening after 30 days of the last study dose. 
Adverse events will be coded using the most recent version of MedDRA. The severity of AEs will be 
graded by investigators according to the CTCAE, Version 5.0 whenever possible.  
The frequency of subjects experiencing a specific adverse event will be tabulated by system organ 
class (SOC) and preferred term (PT). AE leading to study medication discontinuation, AE leading to 
dose reduction/interruption, AE related to study medication, AE leading to death, AEs with CTCAE 
Grade 3 or higher, and SAE will be tabulated and summarized by treatment by SOC and PT. 
If a subject experience the same preferred term multiple times, the event will be counted only once 
and by the greatest severity. 
9.5.7.2 
Laboratory Abnormalities 
The severity of laboratory abnormalities will be graded using the CTCAE whenever possible. 
Descriptive statistics will be used to summarize the laboratory results and the change from baseline 
by visit . Shift tables from baseline to worst severity grade observed during the treatment will be 
displayed . The number and percentage of subjects experiencing a specific laboratory abnormality 
will be tabulated as well. Other tabular and graphical methods may be used to present the results 
for laboratory tests of interest. 
Listings of clinical laboratory data with abnormal flags will be provided by subject, visit, and test. 
9.5.7.3 
Other Safety Assessments 
Height, weight, body mass index, vital signs (heart rate and blood pressure), ECG, and physical 
examination data analyses will be descriptive in nature, and the data will be summarized by visit. 
9.5.8 
Analyses of Secondary Endpoints for Pharmacokinetics 
Pharmacokinetic assessments: 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort 
plasma concentrations collected prior to the morning dose will be summarized. The relationship 
between 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort plasma concentrations 
and selected efficacy and safety outcomes will be explored. Results will be compared with PK data 
from previous studies. PK parameters will be calculated using noncompartmental analysis method: 
AUC(0-t), AUC(0-inf), Cmax, Tmax, CL/F, Vz/F, λz, and t½. 
9.5.9 
Exploratory Endpoints 
Exploratory endpoints will be listed or summarized descriptively as appropriate. 

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9.5.10 
Subgroup Analyses 
No subgroup analyses are planned. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
The Investigator is responsible for ensuring that the clinical study is performed in accordance with 
the Declaration of Helsinki and the International Council for Harmonisation (ICH) GCP guidance 
documents and all relevant local law and applicable regulatory requirements. 
PTC Therapeutics will ensure notification to all competent authorities, ethics committees, and local 
authorities of any substantial protocol amendment according to relevant local law and applicable 
regulatory requirements. PTC Therapeutics will inform the competent authorities, ethics 
committees, and local authorities about non-substantial amendments according to relevant local 
law and applicable regulatory requirements. PTC Therapeutics must receive approval from the 
applicable competent authorities, ethics committees, and local authorities before implementing the 
substantial amendment. 
10.1.1 
Institutional Review Board/Independent Ethics Committee 
Prior to enrollment of subjects into the study, as required by the FDA and other regulatory 
authorities, the protocol and informed consent document will be reviewed and approved by an 
appropriate IRB/IEC. The Investigator will assure that approval of the study protocol will be obtained 
from the IRB/IEC and that all aspects of the IRB/IEC review will be conducted in accordance with 
current regulations. Amendments to the protocol will be subject to the same IRB/IEC review 
requirements as the original protocol. Only changes necessary to eliminate apparent immediate 
hazards to subjects may be initiated prior to IRB/IEC approval. In that event, the Investigator must 
notify the IRB/IEC and PTC Therapeutics in writing within 5 working days after implementation. The 
investigator will also promptly notify the IRB/IEC of any serious, unexpected adverse events, or any 
other information that may affect the safe use of the drug during the course of the study. 
A letter documenting the IRB/IEC approval and a list of the names and titles of the IRB/IEC members 
must be received by PTC Therapeutics prior to the initiation of the study. All correspondence with 
the IRB/IEC should be retained in the Investigator’s study file. 
The Investigator shall submit a progress report, at least once yearly, to the IRB/IEC, and must 
provide a copy to PTC Therapeutics or CRO designee. As soon as possible after completion or 
termination of the study, the Investigator will submit a final report to the IRB/IEC and to PTC 
Therapeutics or CRO designee. This report should include the dates of initiation and completion of 
the study, a description of any changes in study procedures or amendments to the protocol, any 
deviations from the protocol, the number and type of subjects evaluated, the number of subjects 
who discontinued (and the reasons for discontinuation), the number of subjects who completed the 
study, and the results of the study, including a description of any adverse events. PTC Therapeutics 
or CRO designee will assist the Investigator in the preparation of this report, as needed. 

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10.1.2 
Informed Consent Process 
The Investigator will assure that informed consent will be obtained from each subject and/or legal 
guardian prior to study entry and that the informed consent will be obtained in accordance with 
current regulations. 
The Investigator or sub-investigator will give each subject and/or legal guardian full and adequate 
verbal and written information regarding the objectives and procedures of the study and the 
possible risks involved. An informed consent/ document will be provided to each subject and/or 
legal guardian in a language in which the subject or legal guardian is fluent. This information must be 
provided to the subject or legal guardian prior to undertaking any study-related procedure. 
Adequate time should be provided for the subject and/or legal guardian to read the informed 
consent, to understand the risks and benefits of participating in the study, and to ask any questions 
that the subject and/or legal guardian may have about the study. The subject and/or legal guardian 
should be able to ask additional questions as and when needed during the conduct of the study. The 
subject’s and/or legal guardian signature on the informed consent form should be obtained at the 
Investigator site in the presence of the Investigator or a qualified representative (eg, sub-
investigator).  
Each subject or legal guardian will be given a copy of the signed consent form. The original signed 
informed consent forms will be retained by the Investigator with the study records. 
The written subject information must not be changed without prior approval by PTC Therapeutics 
and the IRB/IEC. 
10.1.3 
Study Discontinuation and Closure 
PTC Therapeutics reserves the right to discontinue the study prior to inclusion of the intended 
number of subjects. The Investigator, after consultation with the PTC Therapeutics medical monitor, 
reserves the right to discontinue the study at the Investigator site for safety reasons at any time. 
After a decision to terminate the study, investigators must contact all subjects who are continuing 
their participation in the study and must do so within a time-period set by PTC Therapeutics. As 
directed by PTC Therapeutics, all study materials must be collected, and all electronic data entry 
forms completed to the greatest extent possible. 
10.1.4 
Confidentiality and Privacy 
Research records will be collected and stored in a manner that protects the confidentiality of subject 
information. The names and identities of all research subjects will be kept in strict confidence and 
will not appear on eCRFs, paper CRFs, or other records provided to or retained by PTC Therapeutics 
(or its authorized designee). The names and identities of the subjects need not be divulged; 
however, the records must nevertheless be inspected. This will be accomplished by blanking out the 
subject’s name and replacing the name with the subject’s study identification number on any record 
provided to or retained by PTC Therapeutics. The informed consent form must include appropriate 
statements explaining these requirements. 

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Attention is drawn to the regulations promulgated by the FDA under the Freedom of Information 
Act providing, in part, that information furnished to clinical investigators and the IRB/IEC will be kept 
confidential by the FDA only if maintained in confidence by the clinical investigator and the IRB/IEC. 
By signing this protocol, the Investigator affirms to PTC Therapeutics that the Investigator will 
maintain, in confidence, information furnished by PTC Therapeutics and will divulge such 
information to the IRB/IEC under an appropriate understanding of confidentiality with such board. 
10.1.5 
Clinical Monitoring  
In accordance with 21 CFR Part 312.56 and/or relevant ICH guidelines, PTC Therapeutics or a 
designee will periodically inspect all eCRFs, study documents, research facilities, and clinical 
laboratory facilities associated with this study at mutually convenient times, before, during, and 
after completion of the study. As required by applicable regulations (Responsibilities of Sponsors 
and Investigators), the monitoring visits provide PTC Therapeutics with the opportunity to evaluate 
the progress of the study; verify the accuracy and completeness of data in the eCRFs; ensure that all 
protocol requirements, applicable FDA and other relevant regulations, and investigator’s obligations 
are being fulfilled; and resolve any inconsistencies in the study records. This includes inspection of 
all documents and records required to be maintained by the Investigator, including but not limited 
to medical records (office, clinic, or hospital) for the subjects in this study. The names and identities 
of all research subjects will be kept in strict confidence and will not appear on eCRFs or other 
records provided to or retained by PTC Therapeutics. The Investigator/institution guarantees direct 
access to source documents by PTC Therapeutics and appropriate regulatory authorities. 
It is important that the Investigator and relevant institutional personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
10.1.6 
Quality Assurance and Quality Control 
To ensure compliance with GCP and all applicable regulatory requirements, PTC, PTC’s 
representatives, a regulatory authority or and Institutional Review board may conduct a quality 
assurance audit. Reasons for quality assurance audit may include but are not limited to: random 
selection, geographic proximity, suspected GCP violation, high enrolling site, recurring protocol 
deviations, etc. The purpose of a Sponsor audit or inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the protocol, 
Good Clinical Practice guidelines of the International Council on Harmonisation, and any applicable 
regulatory requirements. The Investigator should contact the Sponsor immediately if contacted by a 
regulatory agency about an inspection. 

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10.1.7 
Data Handling and Record Keeping 
To enable evaluations and/or audits from regulatory authorities or PTC Therapeutics, the 
Investigator agrees to keep accurate and complete records, including the identity of all participating 
subjects (sufficient information to link eCRFs and clinic records/source documents), all original 
signed informed consent forms, electronic copies (ie, CD-ROM, USB, etc) or paper copies of the data 
that have been captured in the electronic data capture for each subject (eCRFs), and detailed 
records of study drug disposition. All records and documents pertaining to the study will be 
maintained by the Investigator until notification is received from PTC Therapeutics that the records 
no longer need to be retained. 
The Investigator must obtain written permission from PTC Therapeutics before disposing of any 
records. The Investigator will promptly notify PTC Therapeutics in the event of accidental loss or 
destruction of any study records. If the Investigator relocates, retires, or for any reason withdraws 
from the study, the study records may be transferred to an acceptable designee, such as another 
investigator, another institution, or to PTC Therapeutics as applicable. 
10.1.8 
Protocol Deviations 
A protocol deviation is defined as any intentional or unintentional change to, or noncompliance 
with, the approved protocol procedures or requirements. Deviations may result from the action or 
inaction of the subject, investigator, or site staff. Examples of deviations include, but are not limited 
to: 
1. 
Failure to adhere to study exclusion and inclusion criteria 
2. 
Failure to comply with dispensing or dosing requirements 
3. 
Use of medications that are specifically prohibited in the protocol 
4. 
Missed or out-of-window visits 
5. 
Drug dosing not administered within the time frame specified in the protocol 
6. 
Failure to adhere to test requirements, including vital signs, laboratory tests, physical 
examinations, PK blood draws, medical history, etc - either tests not done, incorrect tests 
done, or not done within the time frame specified in the protocol 
7. 
Procedural deviations such as incorrect storage of study drug, failure to update the ICF 
when new risks become known, or failure to obtain IRB approvals for the protocol and 
ICF revisions 
Significant deviations are any deviations that impact subject eligibility (ie, protocol 
inclusion/exclusion violations), subject safety or a subject’s ability to continue in the clinical trial. 
At the outset of the study, a process for defining and handling protocol deviations will be 
established with the CRO. This will include determining which deviations will be designated 
significant; thus, requiring immediate notification to the PTC Therapeutics medical monitor and the 
sponsor. 
Prospective deviations (eg, protocol waivers) are prohibited per PTC policy. 

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The Investigator is responsible for seeing that any known protocol deviations are recorded handled 
as agreed. 
10.1.9 
Publication and Data Sharing Policy 
The information developed during the conduct of this clinical study is considered confidential by PTC 
Therapeutics. This information may be disclosed as deemed necessary by PTC Therapeutics. 
PTC Therapeutics intends that the data from this study will be presented and published. The PTC 
Therapeutics staff under the direction of the PTC Therapeutics Chief Medical Officer or designee in 
collaboration with the Investigator will be responsible for writing presentations and manuscripts for 
publication. Investigators will not be allowed to publish or present the data from this study without 
prior agreement with PTC Therapeutics. 
The Investigator is obliged to provide the sponsor with complete test results and all data derived by 
the Investigator from the study. During the study, only the sponsor may make study information 
available to other study Investigators or to regulatory agencies, except as required by law or 
regulation. Except as otherwise allowable in the clinical study site agreement, any public disclosure 
(including publicly accessible websites) related to the protocol or study results, other than study 
recruitment materials and/or advertisements, is the sole responsibility of the Sponsor. 
The sponsor may publish any data and information from the study (including data and information 
generated by the Investigator) without the consent of the Investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and review 
of the document. All publications and presentations must be prepared in accordance with this 
section and the Clinical Study Site Agreement. In the event of any discrepancy between the protocol 
and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
Data from all sites participating in the study will be pooled and analyzed by the sponsor or the 
sponsor’s designee. The first publication of the study results shall be made in conjunction with the 
results from other study sites as a multicenter publication. If a multicenter publication is not 
forthcoming within 24 months of completion of the study at all sites, the Investigator may publish or 
present the results generated at his or her site. 
The Investigator will provide the sponsor with a copy of any proposed publication or presentation 
for review and comment at least 60 days prior to such presentation or submission for publication. 
The sponsor shall inform the Investigator in writing of any changes or deletions in such presentation 
or publication required to protect the sponsor’s confidential and proprietary technical information 
and to address inaccurate data or inappropriate interpretations in the context of any pooled 
multicenter results. At the expiration of such 60-day period, the Investigator may proceed with the 
presentation or submission for publication unless the sponsor has notified the institution or the 
Investigator in writing that such proposed publication or presentation discloses the sponsor’s 
confidential and proprietary technical information. Further, upon the request of the sponsor, the 
Investigator will delay the publication or presentation for an additional 90 days to permit the 
sponsor to take necessary actions to protect its intellectual property interests. 

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10.2 
Additional Considerations 
10.2.1 
Public Notification of Study Conduct 
Consistent with Section 113 of the Food and Drug Modernization Act of 1997 and with requirements 
of the International Committee of Medical Journal Editors as a condition of consideration for 
publication of study results, PTC Therapeutics will be responsible for ensuring that this protocol is 
listed at the ClinicalTrials.gov and EudraCT websites and that information at the websites relating to 
study design and conduct are appropriately updated during the course of the study. In order to 
facilitate this process, investigators will need to supply PTC Therapeutics with appropriate contact 
information for investigator site personnel. 
10.2.2 
Communications with Regulatory Authorities 
PTC Therapeutics will assume responsibility for regulatory interactions with regulatory authorities 
(eg, the FDA, the European Medicines Agency, and/or others). In this regard, PTC Therapeutics will 
maintain an IND for deflazacort in support of the study. In fulfilling this responsibility, PTC 
Therapeutics (or a designee) will collect, assemble, and communicate all required regulatory 
documents (eg, FDA form 1572, investigator financial disclosure forms, protocol and protocol 
amendments, investigator brochures, informed consent documents, annual reports) as required by 
regulation. PTC Therapeutics (or a designee) will also assume responsibility for adverse event 
reporting to regulatory authorities as described in Section 8.4.12. 
10.3 
Protocol Amendment History 
Version 1: 13 December 2018 
Version 2: 28 February 2019 
The overall reason for Version 2: The overall reasons for Version 2 were to include DEXA as an 
additional safety assessment in subjects with LGMD2I. In addition, several editorial changes were 
made to clarify and correct the text. 
Item 
No. 
Protocol 
Section 
Version 2/Update 
Reason/ 
Rationale 
1 
Protocol 
“Patient(s)” was revised to “subject(s)” when referring to this 
protocol. 
“Pill(s)” was revised to “tablet(s)”. 
The following terms were deleted: caregiver(s) (except 
Sections 6.1.2, 6.1.4, and 7.3), assent, parent(s), legally acceptable 
representative 
Editorial revisions (eg, typographical error, punctuation, tenses, 
abbreviations) were incorporated to provide clarity. 
Update 
2 
Protocol 
The title of the protocol was edited to read: “A Multicenter 
Randomized Placebo-Controlled Phase 3 Study on the Safety and 
Efficacy of Deflazacort (Emflaza®) in Subjects with Limb-Girdle 
Muscular Dystrophy 2I (LGMD2I)” 
Update 
3 
Synopsis 
The title of the protocol in the synopsis was corrected and now 
reads: “A Multicenter Randomized Placebo-Controlled Phase 3 
Update 

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Item 
No. 
Protocol 
Section 
Version 2/Update 
Reason/ 
Rationale 
Study on the Safety and Efficacy of Deflazacort (Emflaza®) in 
Subjects with Limb-Girdle Muscular Dystrophy 2I (LGMD2I)” 
4 
Synopsis 
Secondary Endpoints were edited to include DEXA as part of safety 
assessment (secondary endpoint) to evaluate bone density. 
Exploratory endpoints were edited to indicate that change from 
baseline in muscular fat fraction and inflammation of selected lower 
limb muscles will be evaluated at Week 26. 
Inclusion criteria #5 was edited to read: “Must weigh ≥35 to 
≤112.5 kg” 
Exclusion criteria #5 was edited to read: “History of recent bacterial 
infection (including tuberculosis) per discretion of the Investigator” 
Exclusion criteria #9 was edited to indicate a person is excluded 
from the study if they participated in an interventional study within 3-
months prior to baseline of study PTCEMF-GD-004 (Study 004). The 
#9 exclusion criteria now reads: “Participated in an interventional 
clinical trial within the last 3 months prior the Baseline Visit” 
Statistical Methods was edited to read: “Primary analysis will be 
performed using the ITT population from all scheduled visits.” 
Update 
5 
Protocol 
Identifiers 
and Study 
Personnel 
The Clinical trials.gov number has been added. That is 
NCT03783923 
Update 
6 
Synopsis 
and 
Section 
8.1 - 
Schedule 
of Events 
A follow-up phone call for collecting AEs was added to the Schedule 
of Events table.  
DEXA has been added to the Schedule of Events.  
The “notes” for Height/Weight/BMI was edited to read “For study 
inclusion, weight range must be ≥35 to ≤112.5 kg”. 
The “notes” for MRI was edited to indicate qMRI and T2 MRI will 
evaluate muscular fat fraction and inflammation, respectively, of 
selected lower limb muscles. 
Footnote #2 of the Schedule of Events was edited to include the fact 
that the assessment of time to climb 4 stairs must always be 
repeated at the baseline visit and now reads: “Any screening 
procedure completed within and including 7 days of Visit 1, with the 
exception of the time to climb 4 stairs, can serve as baseline and 
does not need to be repeated at Visit 1. The time to climb 4 stairs 
must always be repeated at the baseline visit, and all other visits. 
The second 4 stair climb test should be done a minimum of 
5 minutes after the prior test, or any other physical activity. The 
baseline visit may be split into two consecutive days.” 
Footnote #3 was added to describe Visit 3 procedures when 
switching from the double-blind to open-label phase of the protocol. 
Footnote #4 was edited to more fully describe the early termination 
visit. It describes the follow-up for subjects that are remaining on 
corticosteroid therapy and for those tapering off of deflazacort. 
Footnote #5 was edited to more clearly define the follow-up 
visit/phone call for those subjects that complete the study and 
immediately start receiving commercial deflazacort or another 
corticosteriod. It will be an office for subjects tapering off deflazacort 
Update 

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Item 
No. 
Protocol 
Section 
Version 2/Update 
Reason/ 
Rationale 
to return study drug and for site collection of any AEs and will occur 
4-weeks after last dose of study drug.  
Footnote #7 was edited to indicate that both X-ray and DEXA should 
be performed; however, only an X-ray or DEXA is acceptable if the 
other technology is not available or prohibited per local 
ethical/regulatory decree. 
Footnote #9 was edited to indicate efficacy and PD assessment will 
be performed post-daily dose at each clinic visit, except for the 
baseline visit (Visit 1). At screening and baseline visits, the ability to 
ascend 4 stairs must be >2.5 and <8 seconds. In addition, the 4-stair 
climb will be performed twice at each visit. The second 4-stair climb 
test should be done a minimum of 5 minutes after the prior test (or 
any other physical activity). The two 4-stair climb results must be 
within 20% of one another. If they are not the Medical Monitor 
should be contacted. 
7 
2.2.2 
DEXA has been added as part of safety assessment (secondary 
endpoint) to evaluate bone density. 
Update 
8 
2.2.3 
Exploratory endpoints were edited to indicate that change from 
baseline in muscular fat fraction and inflammation will be evaluated 
from selected lower limb muscles at Week 26. 
Update 
9 
3.1 
Text was added that describes the follow-up visit. 
Text was edited to indicate genotyping may be performed to confirm 
a subject carries a mutation in the FKRP gene if they are lacking 
documentation of an FKRP mutation. 
Text was added to indicate that safety, efficacy, and PD will be 
evaluated at Visit 3 (Week 26).  Placebo subjects will have all 
assessments performed prior to first dose of deflazacort. 
A description of Visit 4 (Week 39), Visit 5/ET and the Follow-up 
Visit/phone call has been added. 
Figure 1 was revised to better portray the follow-up Visit/phone call. 
Update 
10 
4.2 
Inclusion criterial #2 was edited to read: “Male and female subjects 
aged ≥18 years” 
Inclusion criteria #5 was edited to read: “Must weigh ≥35 to 
≤112.5 kg” 
Update 
11 
4.3 
Exclusion criteria #5 was edited to read: “History of recent bacterial 
infection (including tuberculosis) per discretion of the Investigator” 
Exclusion criteria #9 was edited to indicate a person is excluded 
from the study if they participated in an interventional study within 3-
months prior to baseline of study PTCEMF-GD-004 (Study 004). The 
#9 exclusion criteria now reads: “Participated in an interventional 
clinical trial within the last 3 months prior the Baseline Visit” 
Update 
12 
6.1.2 
Text was edited to read specify that in Period 2 dose adjustments 
are permitted in case of tolerability issues at the discretion of the 
Investigator but only after discussion with the PTC Therapeutics 
medical monitor, as described in Section 6.1.2.2 of the protocol. 
Text was edited to clarity that subjects must be instructed not to split 
the tablet(s) and subjects are instructed not to chew the study drug. 
Update 
13 
7.2 
A description of the how patients who terminate early/discontinue 
from the study will be followed-up has been added. 
Update 

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Item 
No. 
Protocol 
Section 
Version 2/Update 
Reason/ 
Rationale 
14 
9.5.10 
Text was edited to read: “Results will be compared with PK data 
from previous studies.  PK parameters will be calculated using 
noncompartmental analysis method: AUC(0-t), AUC(0-inf), Cmax, 
Tmax, CL/F, Vz/F, λz, and t½. 
Update 

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Version 3: 26 September 2019 
The overall reason for Version 3: The overall reasons for Version 3 were to address regulatory 
feedback and to provide updates, including adding an exploratory objective and endpoint, to add 
study visits, to clarify options for subjects at the end of the study and if their blind is broken, and to 
clarify statistical analysis for the key secondary endpoints. In addition, several editorial changes 
were made to clarify and correct the text. 
Item 
No. 
Protocol 
Section 
Version 3/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version were updated. Editorial revisions (eg, 
typographical error, punctuation, tenses, abbreviations) were 
incorporated to provide clarity. Additionally, table numbers and 
cross references to tables were updated based on the new 
Table 1 that was added. 
Update 
2 
Synopsis 
An Exploratory Objective and an Exploratory Endpoint was 
added to include the Individualized Neuromuscular Quality of 
Life (INQoL) questionnaire in subjects with limb-girdle muscular 
dystrophy 2I (LGMD2I). 
Inclusion criteria #3 was edited to clarify the number of seconds 
the subject has to ascend the stairs. 
Exclusion criteria #6 was edited to clarify the criteria for diabetes 
mellitus. 
Update 
3 
Synopsis 
and 
Section 8.1 
- Schedule 
of Events 
The Schedule of Events table was edited to include a Safety 
Call at Week 28, to clarify the clinical laboratory assessments, to 
add Study Procedures for Biomarker testing (Bone Health 
Assays) and the INQoL Questionnaire, to clarify the 
Ophthalmological examination, to clarify the number of seconds 
the subject has to ascend the stairs, and to add visits for ECGs, 
AE/SAE monitoring, and concomitant medications. Edits to the 
table include updates to the footnotes and the numbering of the 
footnotes. 
Update 
4 
1.2 
Text was added to include the date the U.S. Food and Drug 
Administration (FDA) approved deflazacort as a treatment for 
patients ≥2 years with DMD. 
Update 
5 
2.1.3 
An Exploratory Objective was added to include the INQoL 
questionnaire in subjects with LGMD2I. 
Update 
6 
2.2.3 
An Exploratory Endpoint was added to include the INQoL 
questionnaire in subjects with LGMD2I. 
Update 
7 
3.1 
Text was added/edited to include the Week 28 Safety Call, to 
clarify dose adjustments, and to clarify the options for subjects 
at the end of the study.  
The Week 28 Safety Call was also added to Figure 1. 
Update 
8 
3.2 
Text and table were added/edited to describes the benefit/risk 
profile for the use of deflazacort in subjects with LGMD2I. 
Text was added to describe the INQoL questionnaire. 
Update 
9 
4.2 
Inclusion criteria #3 was edited to clarify the number of seconds 
the subject has to ascend the stairs. 
Update 
10 
4.3 
Exclusion criteria #6 was edited to clarify the criteria for diabetes 
mellitus. 
Update 
11 
6.1.2.2 
Text regarding dose adjustments has been modified for clarity. 
Update 

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Item 
No. 
Protocol 
Section 
Version 3/Update 
Reason/ 
Rationale 
The following text was deleted “provided the subject has 
completed the Week 13 visit” from Acne, Behavior Changes, 
Cushingoid Appearance, Gastrointestinal Irritation, 
Hyperglycemia or Glycosuria, Hypertension, Infections 
Potentially Related to Corticosteroid-Mediated 
Immunosuppression, and the Weight gain sections.  
Text in the Hypertension section regarding substantial 
hypertension was modified for clarity. 
In the subsection of Weight Gain, “child/family” was changed to 
“subject” and “/family” was deleted for clarity. 
12 
6.3 
Text was added/edited to clarify the options for subjects whose 
blind has been broken. 
Update 
13 
6.5 
In the Concomitant Therapy section, “study” was changed to 
“follow-up visit” for all medication taken by subjects 30 days prior 
to the first dose of study drug 
Update 
14 
6.5.2 
Text was added to clarify that subjects should not receive live or 
attenuated vaccines during the study. 
Update 
15 
7.1 
Text added/edited to clarify the options for subjects who 
discontinue study drug. 
Update 
16 
8.2 
The following sentence was deleted “Each evaluator will be 
expected to demonstrate reliability and competence by 
assessing a volunteer subject with LGMD2I in accordance with 
the clinical evaluator manual.” 
Update 
17 
8.4.2 
The following sentence was deleted “An event need not be 
reported as an SAE if it exclusively represents a relapse or an 
expected change or progression of the baseline cancer.” 
Update 
18 
9.5.7 
Text was added/deleted to clarify the statistical analysis for the 
key secondary endpoints. 
Update 
19 
10.1 
Text was added to clarify the regulatory, ethical, and study 
oversight considerations. 
Update 
20 
11 
List was updated to add sources to the references list. 
Update 
21 
10.3 
Added Protocol Version History. 
Update 

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Version 4: 24 March 2020 
The overall reason for Version 4: The overall reason for Version 4 was the closure of the study. The 
protocol was amended to allow continuation of treatment for those subjects already on study and 
to allow further enrollment up to approximately 30 subjects. 
Item 
No. 
Protocol 
Section 
Version 4/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version were updated. Editorial revisions (eg, 
typographical error, punctuation, tenses, abbreviations) were 
incorporated to provide clarity. The study title was updated to 
reflect that the study is now an open-label study. 
Update 
2 
Synopsis 
The number of study sites and planned subjects was reduced 
and all mention of placebo treatment was removed. The 
synopsis was aligned with all changes mentioned below.  
Update 
3 
2.1.3 
Pharmacodynamic biomarkers were removed from the 
exploratory objectives and replaced by MRI 
Update 
4 
2.2 
The “key” designation was removed from secondary endpoints, 
the exploratory endpoints were updated to include Dixon MRI, 
and the endpoint regarding T2 mapping was moved from 
Exploratory to Secondary. 
Update 
5 
3.1 
The study design was updated to remove randomization and a 
placebo-controlled period and to reduce the number of study 
sites, subjects, and visits.  
Update 
6 
3.4 
Section added to explain transition from Protocol Version 3.0 to 
Version 4.0. 
Update 
7 
4.2 
Inclusion criterion #3 was amended to read “Ability to ascend 4 
stairs in ≥2.5 seconds and be able to complete the ascent and 
descent at screening and baseline.” 
Update 
8 
5.1 
The number of planned subjects was reduced from 100 to 30. 
Update 
9 
6 
Randomization to placebo was removed. 
Update 
10 
9 
The statistical analyses were updated to remove the comparison 
against placebo. 
Update 
 

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11 
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