Clinical trial NCT04049760
Conditions: Fabry Disease
Keywords: Lysosomal disease migalastat
Sponsor: Amicus Therapeutics
Start date: 2019-10-11; Completion date: 2024-11-29
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a long-term, Open-label Study to Evaluate the Safety, Pharmacodynamics, and Efficacy of Migalastat in Subjects \> 12 Years of Age With Fabry Disease and Amenable GLA Variants

Detailed description:

Arms: arm 1: One migalastat 123 mg capsule equivalent to 150 mg migalastat HCl will be administered every other day (QOD) during the treatment period.
Interventions: intervention 1: migalastat HCl 150 mg
Intervention descriptions: intervention 1: migalastat HCl 150 mg capsule

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Long-Term, Open-Label Study to Evaluate the 
Safety, Pharmacodynamics, and Efficacy of 
Migalastat In Subjects > 12 Years of Age with Fabry 
Disease and Amenable GLA Variants 
 
 
NCT Number: 
NCT04049760 
 
 
Document Date:  
Amendment 2: 19 August 2021 
 


 
 
 
 
CLINICAL STUDY PROTOCOL 
 
A LONG-TERM, OPEN-LABEL STUDY TO EVALUATE 
THE SAFETY, PHARMACODYNAMICS, AND 
EFFICACY OF MIGALASTAT IN SUBJECTS 
> 12 YEARS OF AGE WITH FABRY DISEASE AND 
AMENABLE GLA VARIANTS 
 
Protocol Number: AT1001-036 
 
Version: 3.0, Amendment 2 
 
Protocol Date: 19 August 2021 
 
Original Protocol: 4 February 2019 
Amendment 1: 24 June 2019 
 
EudraCT Number: 2019-000222-21 
 
US IND Number: 068456 
 
Compound: Migalastat 
 
Sponsor 
Amicus Therapeutics UK Limited 
One Globeside,  
Fieldhouse Lane, Marlow 
Buckinghamshire SL7 1HZ 
United Kingdom 
 
 
The information in this document is the property of Amicus Therapeutics and is strictly 
confidential. Neither the document nor the information contained herein may be reproduced or 
disclosed outside of Amicus Therapeutics without the prior written consent of the company, 
except to the extent required under applicable laws or regulations.


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Table 1: 
Serious Adverse Event Reporting 
Role 
Contact Information 
SAE Reporting 
Primary method: 
Safety FAX number:  
+1 866-422-1278 
If the primary method fails, please use: 
Safety Email address: 
safetyreporting@amicusrx.com 
Abbreviation: SAE = serious adverse event  


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1. 
DECLARATIONS OF SPONSOR AND INVESTIGATOR 
1.1. 
Declaration of Sponsor 
This clinical study protocol is subject to critical review and has been approved by the sponsor, 
Amicus Therapeutics (Amicus). 
The information it contains is consistent with the following: 
• the current benefit-risk evaluation of migalastat  
• the moral, ethical, and scientific principles governing clinical research, as set out in 
the current version of the Declaration of Helsinki, the principles of Good Clinical 
Practice (GCP) described in the United States (US) Code of Federal Regulations 
(CFR) Title 21 Parts 50, 54, 56, and 312, and in the International Council on 
Harmonisation (ICH) GCP E6 guidelines 
The investigator will be supplied with details of any significant or new findings related to 
treatment with migalastat. 
Sponsor 
 
Signature:
Date 
 
Amicus Therapeutics 
1.2. 
Declaration of Investigator 
I confirm that I have read this clinical study protocol. I understand it, and I will work according 
to the moral, ethical, and scientific principles governing clinical research, as set out in the current 
version of the Declaration of Helsinki and the principles of GCP described in the US CFR 
Title 21 Parts 50, 54, 56, and 312, and in the ICH GCP E6 guidelines. I will also work in 
accordance with applicable local requirements. 
Investigator 
 
Signature: 
 
 
 
 
Date: 
Printed Name: 
 
PPD
DocuSign Envelope ID: 738FC50D-2277-474B-8A71-3F75B73432AC


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2. 
SYNOPSIS 
Name of Sponsor/Company: 
Amicus Therapeutics (Amicus) 
Name of Investigational Product: 
Migalastat hydrochloride (HCl) 
Name of Active Ingredient: 
Migalastat 
Title of Study: 
A Long-term, Open-label Study to Evaluate the Safety, Pharmacodynamics, and Efficacy of Migalastat 
in Subjects > 12 Years of Age with Fabry Disease and Amenable GLA Variants 
Study Centers: Global, multicenter 
Protocol Number: AT1001-036 
Studied Period: 
Estimated date first subject enrolled: Fourth quarter 2019 
Estimated date last subject completed: Second quarter 2022 
Phase of Development: 
Phase 3b 
Objectives:  
Primary  
• 
to assess the long-term safety of migalastat treatment in pediatric subjects diagnosed with 
Fabry disease and who have variants in the gene encoding α-galactosidase A (α-Gal A) 
(GLA) amenable to treatment with migalastat 
Secondary 
• 
to characterize the pharmacodynamics (PD) of migalastat in pediatric subjects diagnosed 
with Fabry disease and who have GLA variants amenable to treatment with migalastat 
• 
to assess the efficacy of migalastat in pediatric subjects diagnosed with Fabry disease and 
who have GLA variants amenable to treatment with migalastat 
Methodology: 
This is a long-term, open-label, uncontrolled, multicenter study to evaluate the safety, PD, and efficacy 
of migalastat treatment in subjects over 12 years of age with Fabry disease and with amenable GLA 
variants. Subjects will enroll in this study following completion of migalastat Study AT1001-020. 
Enrollment in this study should immediately follow completion of Study AT1001-020 in order to 
maintain the continuity of treatment. As appropriate, assessments performed at the End of Treatment 
visit for Study AT1001-020 will be utilized for Visit 1 (baseline) assessments for this study.  
Subsequent visits for this study will be scheduled every 6 months with interim telephone contacts at 
intervening 3-month intervals in order to monitor safety. In general, subjects must have completed 
Study AT1001-020 to be eligible for enrollment in this study. However, subjects who withdrew from 
that study for a reason not related to the safety or efficacy of migalastat may be eligible to participate 
in this study upon approval by the Amicus medical monitor. 
Subjects will remain on the same dose of migalastat that they were receiving in Study AT1001-020. If 
a subject’s weight decreases to below 43 kg, an unscheduled visit will be arranged 2 to 4 weeks later in 
order to monitor the subject’s weight. 


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Subjects who are eligible and able to receive reimbursed product at the completion of 
Study AT1001-020 or during the current study will be switched to Galafold, if continued treatment 
with migalastat is desired. Subjects who are unable to secure reimbursed product may continue 
treatment in the study, or via an early access or other program. Regardless of treatment choice, subjects 
may also enroll in the Fabry Registry that is being conducted under a separate protocol. 
Number of Subjects (Planned): 
The number of subjects to be enrolled will be dependent on the number of eligible subjects completing 
Study AT1001-020 and who consent to enroll in this open-label extension study. 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria: 
Subjects must meet all of the following criteria to be considered for enrollment in the study: 
1. Male or female subjects diagnosed with Fabry disease > 12 years of age who completed 
Study AT1001-020  
2. Subject’s parent or legally-authorized representative is willing and able to provide written 
informed consent and authorization for use and disclosure of personal health information or 
research-related health information, and subject provides assent, if applicable 
3. If of reproductive potential, both male and female subjects agree to use a medically accepted 
method of contraception throughout the duration of the study and for up to 30 days after their 
last dose of migalastat 
Exclusion Criteria: 
Subjects who meet any of the following criteria will be excluded from participating in the study: 
1. Subject’s last available estimated glomerular filtration rate (eGFR) in the previous study was 
< 60 mL/min/1.73 m2 
2. Subject has advanced kidney disease requiring dialysis or kidney transplantation 
3. Subject received any investigational/experimental drug, biologic, or device within 30 days 
before baseline, with the exception of migalastat 
4. Subject anticipates starting gene therapy during the study period 
5. Subject has any intercurrent illness or condition at Visit 1 that may preclude the subject from 
fulfilling the protocol requirements or suggests to the investigator that the potential subject 
may have an unacceptable risk by participating in this study 
6. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other 
iminosugars (eg, miglustat, miglitol) 
7. Subject requires treatment with Replagal® (agalsidase alfa) or Fabrazyme® (agalsidase beta)  
8. Subject requires treatment with Glyset® (miglitol) or Zavesca® (miglustat) 
9. Female subject is pregnant or breast-feeding, or is planning to become pregnant during the 
study period  
10. In the opinion of the investigator, the subject and/or parent or legally-authorized representative 
is unlikely or unable to comply with the study requirements 


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Investigational Product, Dosage, and Mode of Administration: 
Migalastat will be supplied as 150-mg capsules. Migalastat capsules contain 123 mg migalastat free 
base, which is equivalent to 150 mg migalastat HCl.  
Administration 
Migalastat will be administered every other day (QOD) during the treatment period. Capsules are to be 
taken with water at the same time of day during the QOD dosing schedule. 
Subjects will be instructed not to eat for at least 2 hours before and for 2 hours after administration of 
study drug. Water can be consumed during this period. 
Duration of Treatment: 
Subjects will continue on the study until the date of regulatory approval or marketing authorization for 
pediatric patients with Fabry disease and availability of reimbursed product in the participating 
subject’s country, or study termination by Amicus. Since subjects will be entering this study as they 
complete Study AT1001-020, the duration of treatment will vary among subjects. 
Reference Therapy, Dosage and Mode of Administration: 
There is no reference therapy for this study. 
Criteria for Evaluation: 
Safety Assessments: 
Safety assessments include monitoring of adverse events (AEs), clinical laboratory tests, vital signs, 
physical examinations, body weight and height, 12-lead electrocardiograms (ECGs), echocardiograms, 
and Tanner staging of sexual development. 
Safety endpoints are as follows: 
• 
incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), 
and AEs leading to discontinuation of study drug 
• 
change from baseline in clinical laboratory test results over time 
• 
change from baseline in vital signs over time 
• 
change from baseline in physical examination findings over time 
• 
change from baseline in body weight and height over time 
• 
change from baseline in ECG results over time 
• 
change from baseline in echocardiogram parameters over time 
• 
change from baseline in Tanner Stage  
Pharmacodynamic Assessments:  
The primary PD biomarker to be evaluated in this study is lyso-Gb3 levels in plasma. Exploratory 
evaluation of lyso-Gb3 analogues and other potential Fabry biomarkers (non-genetic) also may be 
explored from these samples.  
The PD endpoint is change from baseline in plasma levels of lyso-Gb3. 
Efficacy Assessments: 
Efficacy assessments include eGFR, urine protein and albumin levels, left ventricular mass index 
(LVMi) and other cardiac parameters using echocardiograms, and subject questionnaires 
(Fabry-Specific Pediatric Health and Pain Questionnaire [FPHPQ], and Pediatric Quality of Life 
Inventory™ [PedsQL™]).  


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Efficacy endpoints are as follows: 
• 
change from baseline in eGFR (Schwartz formula)  
• 
change from baseline in urine protein and albumin levels  
• 
change from baseline in LVMi  
• 
change from baseline in FPHPQ scores  
• 
change from baseline in PedsQL scores 
For analysis purposes, baseline value for efficacy endpoints for subjects enrolled in this study will be 
the baseline visit of Study AT1001-020. 
Note: Estimated GFR will be calculated using the Schwartz formula throughout the study, regardless of 
the subject's age at the time of assessment. For subjects ≥ 18 years of age, the Schwartz formula will be 
applied by the sponsor at the time the value is entered into the database. 
Statistical Methods:  
The safety population will include all subjects who receive at least 1 dose or partial dose of study drug. 
All safety and PD analyses will be performed using the safety population. 
The intent-to-treat population will include all enrolled subjects. All efficacy analyses will be performed 
using the intent-to-treat population.  
Data will be summarized using descriptive statistics. Continuous variables will be summarized by 
number of subjects, mean, standard deviation, median, minimum, and maximum values. Discrete 
variables will be summarized by counts and percentages. In general, data will be summarized by age 
group at baseline, by sex, and combined across all subjects. 


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3. 
TABLE OF CONTENTS AND LIST OF TABLES 
TABLE OF CONTENTS 
1. 
DECLARATIONS OF SPONSOR AND INVESTIGATOR.......................................3 
1.1. 
Declaration of Sponsor .................................................................................................3 
1.2. 
Declaration of Investigator ...........................................................................................3 
2. 
SYNOPSIS ...................................................................................................................4 
3. 
TABLE OF CONTENTS AND LIST OF TABLES ....................................................8 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................13 
5. 
INTRODUCTION AND STUDY RATIONALE ......................................................14 
5.1. 
Fabry Disease ..............................................................................................................14 
5.2. 
Migalastat ...................................................................................................................15 
5.3. 
Summary of Nonclinical and Clinical Safety Data .....................................................15 
5.3.1. 
Nonclinical Data .........................................................................................................15 
5.3.2. 
Clinical Data ...............................................................................................................16 
5.3.2.1. 
Pharmacology .............................................................................................................16 
5.3.2.2. 
Safety ..........................................................................................................................17 
5.4. 
Study Rationale ...........................................................................................................17 
5.5. 
Dose Selection ............................................................................................................18 
6. 
OBJECTIVES AND PURPOSE .................................................................................19 
6.1. 
Primary Objective .......................................................................................................19 
6.2. 
Secondary Objectives .................................................................................................19 
7. 
INVESTIGATIONAL PLAN .....................................................................................20 
7.1. 
Study Design ...............................................................................................................20 
7.2. 
Duration of Treatment ................................................................................................20 
7.3. 
Details of Study Treatment .........................................................................................20 
7.3.1. 
Administration of Study Treatment ............................................................................20 
7.3.2. 
Study Drug Interruptions ............................................................................................21 
7.3.3. 
Treatment Compliance ................................................................................................21 
7.4. 
Concomitant Medications ...........................................................................................21 
7.5. 
Prohibited Medications ...............................................................................................21 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................22 
8.1. 
Number of Subjects ....................................................................................................22 


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8.2. 
Eligibility Criteria .......................................................................................................22 
8.2.1. 
Inclusion Criteria ........................................................................................................22 
8.2.2. 
Exclusion Criteria .......................................................................................................22 
8.3. 
Withdrawal Criteria ....................................................................................................23 
8.3.1. 
Reasons for Discontinuation/Withdrawal ...................................................................23 
8.3.2. 
Handling of Withdrawals ............................................................................................23 
8.4. 
Subjects of Childbearing Potential .............................................................................24 
9. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................26 
9.1. 
Description of Study Visits .........................................................................................29 
9.1.1. 
Unscheduled Visits .....................................................................................................29 
9.1.2. 
Baseline Visit ..............................................................................................................29 
9.1.3. 
Treatment Period Visits/Telephone Contacts .............................................................29 
9.1.4. 
Early Termination Visit ..............................................................................................30 
9.1.5. 
30-day Safety Follow-up Visit ....................................................................................30 
9.2. 
Description of Study Assessments ..............................................................................30 
9.2.1. 
Medical History ..........................................................................................................30 
9.2.2. 
Safety Assessments .....................................................................................................30 
9.2.2.1. 
Adverse Events and/or Serious Adverse Events .........................................................30 
9.2.2.2. 
Clinical Laboratory Tests ...........................................................................................30 
9.2.2.3. 
Vital Signs ..................................................................................................................32 
9.2.2.4. 
Physical Examination .................................................................................................32 
9.2.2.5. 
Body Weight and Height ............................................................................................32 
9.2.2.6. 
Electrocardiograms .....................................................................................................32 
9.2.2.7. 
Echocardiogram ..........................................................................................................32 
9.2.2.8. 
Tanner Staging ............................................................................................................32 
9.2.2.9. 
Concomitant Medications and Procedures .................................................................33 
9.2.3. 
Pharmacodynamic Assessments .................................................................................33 
9.2.4. 
Efficacy Assessments .................................................................................................33 
9.2.4.1. 
Estimated Glomerular Filtration Rate .........................................................................33 
9.2.4.2. 
Urine Protein and Albumin Levels .............................................................................33 
9.2.4.3. 
Echocardiogram ..........................................................................................................33 
9.2.4.4. 
Subject Questionnaires ...............................................................................................33 
10. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ..................................35 


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10.1. 
Definitions ..................................................................................................................35 
10.1.1. 
Adverse Event .............................................................................................................35 
10.1.2. 
Serious Adverse Event ................................................................................................36 
10.2. 
Relationship to Study Drug ........................................................................................37 
10.3. 
Severity Assessment ...................................................................................................38 
10.4. 
Reporting Events ........................................................................................................38 
10.4.1. 
Reporting Adverse Events ..........................................................................................38 
10.4.2. 
Reporting Serious Adverse Events .............................................................................38 
10.4.3. 
Additional Reporting Requirements for Suspected Unexpected Serious 
Adverse Reaction ........................................................................................................39 
10.5. 
Other Reporting Situations .........................................................................................40 
10.5.1. 
Pregnancy ...................................................................................................................40 
10.5.2. 
Medication Errors, Including Overdose and Under Dose ..........................................40 
10.5.3. 
Reporting of Possible Study Drug Product Quality Defects ......................................40 
11. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS .............................41 
11.1. 
Endpoints ....................................................................................................................41 
11.1.1. 
Safety Endpoints .........................................................................................................41 
11.1.2. 
Pharmacodynamic Endpoints .....................................................................................41 
11.1.3. 
Efficacy Endpoints ......................................................................................................41 
11.2. 
Sample Size Considerations .......................................................................................41 
11.3. 
Data Analysis Considerations .....................................................................................42 
11.3.1. 
Analysis Populations ..................................................................................................42 
11.3.1.1. 
Safety Population ........................................................................................................42 
11.3.1.2. 
Intent-to-treat Population ............................................................................................42 
11.4. 
Statistical Methods ......................................................................................................42 
11.4.1. 
Interim Analysis ..........................................................................................................42 
11.4.2. 
Baseline Demographic and Subject Characteristics ...................................................42 
11.4.3. 
Subject Disposition .....................................................................................................43 
11.4.4. 
Safety Analyses ..........................................................................................................43 
11.4.4.1. 
Exposure .....................................................................................................................43 
11.4.4.2. 
Adverse Events ...........................................................................................................43 
11.4.4.3. 
Laboratory Data ..........................................................................................................43 
11.4.4.4. 
Vital Signs ..................................................................................................................43 


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11.4.4.5. 
Physical Examinations ................................................................................................44 
11.4.4.6. 
Electrocardiograms .....................................................................................................44 
11.4.4.7. 
Echocardiograms ........................................................................................................44 
11.4.4.8. 
Concomitant Medications ...........................................................................................44 
11.4.5. 
Pharmacodynamic Analyses .......................................................................................45 
11.4.6. 
Efficacy Analyses .......................................................................................................45 
12. 
STUDY TREATMENTS............................................................................................46 
12.1. 
Description of Study Drug ..........................................................................................46 
12.2. 
Packaging and Labeling ..............................................................................................46 
12.3. 
Study Drug Accountability .........................................................................................46 
12.3.1. 
Handling, Storage, Return, and Disposal of Study Drugs ..........................................47 
12.3.2. 
Shipment, Return, and Disposal of Investigational Product .......................................47 
13. 
STUDY MANAGEMENT .........................................................................................48 
13.1. 
Documentation of Protocol-required Information and Study Findings ......................48 
13.2. 
Data Management .......................................................................................................48 
13.3. 
Study Monitoring, Source Data Verification, and Onsite Audits ...............................48 
13.4. 
Study Site Closure ......................................................................................................49 
13.5. 
Records Retention .......................................................................................................49 
13.6. 
Use of Study Findings ................................................................................................50 
14. 
STUDY CONDUCT CONSIDERATIONS ...............................................................51 
14.1. 
Regulatory and Ethical Considerations ......................................................................51 
14.1.1. 
Independent Ethics Committees/Institutional Review Boards/Research 
Ethics Boards Approval and Study Compliance ........................................................51 
14.1.2. 
Informed Consent/Assent Information .......................................................................51 
14.1.3. 
Ongoing Information for Independent Ethics Committee/Institutional 
Review Board .............................................................................................................52 
14.1.4. 
Posting of Information on Publicly Available Clinical Trial Registers ......................52 
14.1.5. 
Quality Control ...........................................................................................................52 
14.1.6. 
Quality Assurance .......................................................................................................53 
14.1.7. 
Confidentiality ............................................................................................................53 
14.1.8. 
Protocols Amendments and Deviations ......................................................................53 
14.1.9. 
Delegation of Investigator Duties ...............................................................................54 
14.2. 
Legal and Financial Aspects .......................................................................................54 


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14.2.1. 
Liability and Insurance ...............................................................................................54 
14.2.2. 
Financial Disclosure ...................................................................................................54 
15. 
REFERENCES ...........................................................................................................56 
16. 
APPENDICES ............................................................................................................58 
APPENDIX A. TANNER STAGING ........................................................................................58 
 
LIST OF TABLES 
Table 1: 
Serious Adverse Event Reporting .................................................................................2 
Table 2: 
Schedule of Assessments ............................................................................................27 
Table 3: 
Total Blood Volume to be Collected (as Scheduled) per Subject per Year ...............29 
Table 4: 
Clinical Laboratory Parameters ..................................................................................31 
Table 5: 
Investigational Product (Capsule) ...............................................................................46 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Term 
Definition 
α-Gal A 
α-galactosidase A 
AE 
adverse event 
AUC 
area under the plasma concentration-time curve 
BID 
bis in die (twice daily) 
CFR 
Code of Federal Regulations 
CRO 
contract research organization 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EU 
European Union 
FPHPQ 
Fabry-Specific Pediatric Health and Pain Questionnaire 
GCP 
Good Clinical Practice 
GL-3 
globotriaosylceramide 
GLA 
gene encoding α-galactosidase A 
HCl 
hydrochloride 
ICH 
International Conference on Harmonisation 
IND 
Investigational New Drug 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
lyso-Gb3 
globotriaosylsphingosine 
LVMi 
left ventricular mass index 
PCS 
potentially clinically significant 
PD 
pharmacodynamic  
PedsQL™ 
Pediatric Quality of Life Inventory™ 
QOD 
quaque altera die (once every other day) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
WBC 
white blood cell 


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5. 
INTRODUCTION AND STUDY RATIONALE 
5.1. 
Fabry Disease 
Fabry disease is a rare, progressive and devastating X-linked lysosomal storage disorder 
affecting males and females, with an estimated prevalence of 1:117,000 up to 1:40,000 live 
births (Desnick, Schindler 2001; Germain 2010; Meikle, Hopwood et al. 1999; Eurordis 2005). 
Newborn screening studies have identified a higher incidence of variants in GLA, the gene 
encoding the lysosomal enzyme, α-galactosidase A (α-Gal A) (Spada, Pagliardini et al. 2006; 
Mechtler, Stary et al. 2012), although the impact of these findings on disease prevalence has not 
been established. Disease-causing variants in the GLA gene result in a deficiency of α-Gal A, 
which is required for glycosphingolipid metabolism (Brady, Gal et al. 1967). Beginning early in 
life, the reduction in α-Gal A activity results in an accumulation of glycosphingolipids, including 
globotriaosylceramide (GL-3) and plasma globotriaosylsphingosine (lyso-Gb3), and leads to the 
symptoms and life-limiting sequelae of Fabry disease, which include pain, gastrointestinal 
symptoms, renal failure, cardiomyopathy, cerebrovascular events, and early mortality 
(Germain 2010). Early initiation of therapy and lifelong treatment may provide an opportunity to 
slow disease progression and prolong life expectancy. 
Fabry disease encompasses a spectrum of disease severity and age of onset, although it has 
traditionally been divided into 2 main phenotypes, “classic” and “late-onset” (Desnick, Ioannou 
et al. 2001; Filoni, Caciotti et al. 2010; Topaloglu, Ashley et al. 1999; Shabbeer, Yasuda et al. 
2002; Shabbeer, Yasuda et al. 2006; Ishii, Chang et al. 2007). The classic phenotype has been 
ascribed primarily to males with undetectable to low α-Gal A activity and is associated with 
earlier onset of renal, cardiac, and/or cerebrovascular manifestations. The late-onset phenotype 
has been ascribed primarily to males and females with higher residual α-Gal A activity and is 
associated with later onset of disease. Heterozygous female carriers typically express the 
late-onset phenotype, but may also display the classic phenotype depending on the pattern of 
X-chromosome inactivation. 
More than 1000 Fabry disease-causing GLA variants have been identified (data on file). 
Approximately 67% are missense variants, resulting in single amino acid substitutions in the 
α-Gal A enzyme (Germain 2010; Gal, Schäfer et al. 2006). Missense GLA variants often result in 
the production of abnormally folded and unstable forms of α-Gal A (Fan, Ishii et al. 1999; 
Ishii, Chang et al. 2007) and the majority are associated with the classic phenotype 
(Filoni, Caciotti et al. 2010; Topaloglu, Ashley et al. 1999; Shabbeer, Yasuda et al. 2002; 
Shabbeer, Yasuda et al. 2006; Ishii, Chang et al. 2007). Normal cellular quality control 
mechanisms in the endoplasmic reticulum block the transit of these abnormal proteins to 
lysosomes and target them for premature degradation and elimination. Many missense mutant 
forms are targets for migalastat, an α-Gal A-specific pharmacological chaperone (Yam, Zuber 
et al. 2005; Yam, Bosshard et al. 2006; Benjamin, Flanagan et al. 2009). 
Note: In the Migalastat Clinical Development Program, all subjects were previously, and 
continue to be, required to have a GLA variant that is amenable to migalastat treatment. 
Historically in Amicus documents, these variants were referred to as “mutations.” Mutation 
will be referred to as “variant” in all new or revised Amicus sponsored protocols, consistent 
with the guidelines of the American Medical College of Genetics and Genomics. 


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5.2. 
Migalastat 
Migalastat, a low molecular weight iminosugar, is an analogue of the terminal galactose of GL-3. 
Nonclinical in vitro and in vivo pharmacologic studies have demonstrated that migalastat acts as 
a pharmacological chaperone, selectively and reversibly binding with high affinity to the active 
site of wild-type α-Gal A and specific mutant forms of α-Gal A (Ishii, Chang et al. 2007), the 
genotypes of which are referred to as amenable variants. Migalastat is a precision medicine 
targeted specifically to patients with Fabry disease who express specific mutant variants of the 
GLA gene that can be functionally restored by migalastat. Migalastat binding stabilizes these 
mutant forms of α-Gal A in the endoplasmic reticulum, facilitating their proper trafficking to 
lysosomes where dissociation of migalastat allows the now active α-Gal A to reduce the level of 
GL-3 and other substrates (Yam, Zuber et al. 2005; Yam, Bosshard et al. 2006; Benjamin, 
Flanagan et al. 2009).  
The Migalastat Amenability Assay, which is compliant with Good Laboratory Practices and has 
been clinically validated, was developed to identify patients with variants amenable to treatment 
with migalastat. Amenable variants are those that translate to mutant forms of the enzyme and 
that show a relative increase in enzyme activity that is ≥ 1.20-fold above the baseline value and 
an absolute increase of ≥ 3.0% of wild-type at a threshold of 10 μM migalastat in the Migalastat 
Amenability Assay (Benjamin, Delle Valle et al. 2017). Approximately 35% to 50% of patients 
with Fabry disease are currently estimated to have amenable variants, the majority of which are 
associated with the classic phenotype of the disease (Benjamin, Flanagan et al. 2009; 
Filoni, Caciotti et al. 2010; Germain, Shabbeer et al. 2002; Shabbeer, Yasuda et al. 2006). 
5.3. 
Summary of Nonclinical and Clinical Safety Data  
5.3.1. 
Nonclinical Data  
Available results from single-dose and repeat-dose nonclinical studies with migalastat having a 
wide margin of safety (ie, with doses that were ≥ 25-fold higher than those used in clinical 
studies) suggest no specific hazard regarding chronic toxicity to humans, based on values for 
area under the plasma concentration-time curve (AUC), with the exception of possible transient, 
fully reversible male infertility. In addition, a 39-week toxicity study in juvenile monkeys did not 
demonstrate a concern for toxicity, suggesting that migalastat does not induce adverse effects in 
the developing organ systems evaluated in that study. 
In nonclinical studies using hR301Q α-Gal A Tg/knockout mice, a 30-mg/kg dose of migalastat 
was found to be optimal (AUC, 18400 ng•hr/mL; Study RR1001-08); at this dose, significant 
increases in α-Gal A activity and GL-3 substrate reduction were demonstrated across all tissues. 
At higher doses, no further improvements were observed.  
Nonclinical studies also demonstrated that greater GL-3 reductions were observed with a 
regimen less frequent than daily administration, including every-other-day administration. 
In regard to safety, the pivotal chronic dosing studies utilized rats and monkeys of approximately 
6 weeks and 21 to 27 months of age, respectively, at the initiation of dosing. Developmentally, 
this corresponds to a human of approximately 12 years of age with respect to the rat, and less 
than 12 years of age with respect to the monkey (Beck, Padgett et al. 2006). 


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The main finding identified with migalastat in nonclinical studies was reversible infertility in 
male rats. Full fertility returned to the previously migalastat-treated animals after a 4 week 
washout period, a period of less than a full spermatogenic cycle (> 2 months). No effects on 
sperm count, morphology, or motility were detected to account for the reduction in male fertility. 
These observations with migalastat, and the published information on other iminosugars 
including miglustat, strongly suggest that the infertility is due to effects on sperm maturation or 
function (Zavesca Package Insert 2017). Numerous studies indicate that these effects are related 
to sexual maturation processes that only occur after puberty, and not an adverse effect on 
testicular spermatogenesis. There is no indication of adverse effects on the germinal epithelium 
or testicular spermatogenesis that would be of particular concern for the proposed pediatric use 
of migalastat. There were also no effects on sperm motility, count or morphology in rats, and no 
changes in organ weights or pathology in the testes or accessory sex organs reported in rats, 
mice, or monkeys. In addition, there were also no observations suggesting that the reproductive 
effects may be mediated by endocrine disruption which also would be of importance in 
developing animals and relevant for the proposed use in young people. Based on these findings, 
the fertility effects are not considered to pose any increased risk to pediatric patients compared to 
adults. In addition, a 39-week toxicity study in juvenile monkeys did not demonstrate adverse 
effects in the developing organ systems evaluated in that study. 
5.3.2. 
Clinical Data 
Clinical data for migalastat are available for healthy adults, and adolescents (16 to < 18 years of 
age) and adult patients with Fabry disease. 
5.3.2.1. 
Pharmacology 
In adult subjects with Fabry disease and amenable variants, the dose and regimen of migalastat 
were selected to obtain the optimal balance between migalastat concentration and its subsequent 
clearance, in order to maximize in situ α-Gal A activity and GL-3 substrate reduction. Dose 
selection was based on findings from nonclinical and clinical studies. Exposure observed 
following a single oral dose of migalastat hydrochloride (HCl) 150 mg in humans (AUC, 
13521 ng•hr/mL) was similar to that observed after a 30-mg/kg dose in mice (see Section 5.3.1).  
In a Phase 1 repeat-dose study in healthy subjects, greater increases in wild-type α-Gal A activity 
levels were observed in white blood cells (WBCs) after oral administration of 150 mg 
migalastat HCl twice daily (BID) for 7 days as compared to that seen after 50 mg BID. In five 
Phase 2 studies, ranges of regimens and doses were explored in 27 subjects (18 males and 
9 females): BID (25, 100, 250 mg), once daily (50 mg), once every other day (QOD) (50, 150, 
250 mg), and 3 days on/4 days off (250, 500 mg). In these studies, 150 mg migalastat HCl QOD 
resulted in the best balance of substrate (ie, urine GL-3) reduction and safety in subjects with 
amenable variants compared with other doses and regimens. Treatment with 150 mg 
migalastat HCl QOD also resulted in decreases in kidney interstitial capillary GL-3 levels and 
was associated with long-term stability of renal function. In Study FAB-CL-205, when subjects 
were switched from 150 mg migalastat HCl QOD to higher, less frequent doses (250/500 mg 
3 days on/4 days off), no further increases in WBC α-Gal A activity or reductions in urine GL-3 
levels were observed. Additionally, a higher incidence of treatment-related adverse events (AEs) 
was observed at the 250- and 500-mg dose levels. On the basis of these collective data, 


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150 mg QOD was selected as the dose and regimen for Phase 3 studies of migalastat in adults 
(ie, ≥ 16 years of age).  
Migalastat is to be taken 2 hours before and 2 hours after a meal based on 2 food-effect studies 
(Study FAB-CL-103 and AT1001-016), which demonstrated that food reduces the bioavailability 
of migalastat as assessed using area under the plasma concentration-time curve from 
time 0 extrapolated to infinity (AUC0-∞), maximum observed plasma concentration (Cmax), and 
time to reach maximum observed plasma concentration (tmax) (Johnson, Mudd et al. 2015). 
Details of these studies are provided in the Investigator’s Brochure. 
5.3.2.2. 
Safety 
Migalastat has a favorable safety profile in adults based on results from a comprehensive 
development program. The extent of exposure to migalastat among subjects with Fabry disease 
in Phase 2 and Phase 3 studies is approximately 595.2 patient-years, with the longest subject 
exposure in a clinical trial being 12.76 years. The subject transferred to commercial migalastat 
(Galafold®) in 2018. 
No treatment-related deaths have been reported in clinical studies, and most serious adverse 
events (SAEs) were not considered treatment-related. In Phase 1 studies, the most frequently 
reported AE was headache. In completed Phase 2 studies in subjects with Fabry disease 
(Study FAB-CL-201 through Study FAB-CL-204), the most frequently reported AEs were 
headache, arthralgia, diarrhea, and nausea. In completed Phase 3 studies in subjects with Fabry 
disease (Study AT1001-011, Study AT1001-012, and Study AT1001-041), the most frequently 
reported AEs were diarrhea, headache, arthralgia, pain in extremity, nausea, fatigue, 
nasopharyngitis, dizziness, and influenza, though the order by frequency was not necessarily the 
same in all 3 studies. 
5.4. 
Study Rationale 
This is a Phase 3b, open-label, uncontrolled, multicenter study to evaluate the long-term safety, 
pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric subjects over 12 years 
of age with Fabry disease and amenable GLA variants. The youngest pediatric subjects included 
in previous studies with migalastat were 16 years of age. 
Early signs and symptoms of Fabry disease tend to manifest during childhood and adolescent 
years (ie, < 18 years), particularly in males with the classic phenotype, and are followed later in 
life by the development of overt kidney, cardiovascular, and central nervous system 
complications. In the 2 largest disease registries, the Fabry Outcome Survey and the Fabry 
Registry (Ramaswami, Whybra et al. 2006; Hopkin, Bissler et al. 2008), the median age of 
symptom onset is reported to be approximately 6 years in boys and 8 to 9 years in girls. 
Diagnosis is often delayed due to the different manifestations of the disease, its relative rarity, 
and the lack of clinical awareness of the condition, making the median age of diagnosis 
approximately 9 years in boys and 9 to 13 years in girls. 
Data from these Fabry disease registries indicate that the most common symptom among 
pediatric subjects was neuropathic pain (eg, episodic pain crises, chronic pain, and 
acroparesthesia), which was reported more frequently by boys than by girls (58.8% versus 
40.5%), and with an earlier age of onset (7 versus 9 years). The gastrointestinal tract was the 


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second most commonly involved organ system with 18% of children experiencing signs and 
symptoms (eg, abdominal pain and diarrhea); the median age at onset of symptoms was 5 years 
in boys and 9.5 years in girls. The next most common sign was skin findings such as 
angiokeratomas. As with neuropathic pain, these symptoms and signs were more prevalent in 
boys than girls and occurred at an earlier age of onset. 
Renal involvement appears less commonly in the younger population; however, a limited 
number of older adolescents have been reported to have impaired glomerular filtration rate 
(GFR), proteinuria, and hyperfiltration, along with cardiac abnormalities, pain, and 
gastrointestinal symptoms.  
Considering the young age of symptom onset, diagnosis, and the progressive nature of Fabry 
disease, early intervention and treatment for pediatric patients could be important in slowing the 
progression of this disease (Hopkin, Jefferies et al. 2016). This study provides continued 
migalastat treatment for pediatric subjects previously enrolled in Study AT1001-020, allowing 
for continued assessment of safety and efficacy in this population. 
5.5. 
Dose Selection 
The dose regimen of migalastat proposed for evaluation in pediatric subjects with Fabry disease 
(150 mg QOD) weighing ≥ 45 kg (99 pounds) is the same as the adult dose and is supported by 
simulation results from a population pharmacokinetic model derived using data from adults, 
based on body weight (Migalastat Abbreviated Report of the Simulations of Migalastat in 
Pediatric Patients with Fabry Disease, 20 October 2016). 


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6. 
OBJECTIVES AND PURPOSE 
6.1. 
Primary Objective 
The primary objective of this study is as follows:  
• to assess the long-term safety of migalastat treatment in pediatric subjects diagnosed 
with Fabry disease and who have variants in the gene encoding α-Gal A amenable to 
treatment with migalastat 
6.2. 
Secondary Objectives 
The secondary objectives of this study are as follows: 
• to characterize the PD of migalastat in pediatric subjects diagnosed with Fabry 
disease and who have GLA variants amenable to treatment with migalastat 
• to assess the efficacy of migalastat in pediatric subjects diagnosed with Fabry disease 
and who have GLA variants amenable to treatment with migalastat  


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Study Design  
This is a long-term, open-label, uncontrolled, multicenter study to evaluate the safety, PD, and 
efficacy of migalastat treatment in pediatric subjects over 12 years of age with Fabry disease and 
with amenable GLA variants. Subjects will enroll in this study following completion of 
migalastat Study AT1001-020.  
Enrollment in this study should immediately follow completion of Study AT1001-020 in order to 
maintain the continuity of treatment. As appropriate, assessments performed at the End of 
Treatment visit for Study AT1001-020 will be utilized for Visit 1 (baseline) assessments for this 
study.  
Subsequent visits for this study will be scheduled every 6 months with interim telephone contacts 
at intervening 3-month intervals in order to monitor safety. In general, subjects must have 
completed Study AT1001-020 to be eligible for enrollment in this study. However, subjects who 
withdrew from the prior study for a reason not related to the safety or efficacy of migalastat may 
be eligible to participate in this study upon approval by the Amicus medical monitor. 
Subjects will remain on the same dose of migalastat that they were receiving in 
Study AT1001-020. If a subject’s weight decreases to below 43 kg, an unscheduled visit will be 
arranged 2 to 4 weeks later in order to monitor the subject’s weight. 
Subjects who are eligible and able to receive reimbursed product at the completion of 
Study AT1001-020 or during the current study will be switched to Galafold, if continued 
treatment with migalastat is desired. Subjects who are unable to secure reimbursed product may 
continue treatment in the study, or via an early access or other program. Regardless of treatment 
choice, subjects may also enroll in the Fabry Registry that is being conducted under a separate 
protocol. 
7.2. 
Duration of Treatment 
Subjects will continue on the study until the date of regulatory approval or marketing 
authorization for pediatric patients with Fabry disease and availability of reimbursed product in 
the participating subject’s country, or study termination by Amicus. Since subjects will be 
entering this study as they complete Study AT1001-020, the duration of treatment will vary 
among subjects. 
7.3. 
Details of Study Treatment 
Migalastat will be supplied as 150-mg capsules. Migalastat capsules contain 123 mg migalastat 
free base, which is equivalent to 150 mg migalastat HCl.  
7.3.1. 
Administration of Study Treatment 
Migalastat will be administered QOD during the treatment period. Capsules are to be taken with 
water at the same time of day during the QOD dosing schedule. 


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Subjects will be instructed not to eat for at least 2 hours before and for 2 hours after 
administration of study drug. Water can be consumed during this period. 
Study drug should not be taken on 2 consecutive days. If a dose is missed entirely for the day, 
the subject should take the missed dose of study drug only if it is within 12 hours of the time the 
dose normally is taken. If more than 12 hours have passed, the subject should resume taking 
study drug at the next planned dosing day and time according to the every-other-day dosing 
schedule.  
7.3.2. 
Study Drug Interruptions 
The investigator may choose to interrupt administration of study drug in case of an AE 
(eg, abnormal result of an assessment or laboratory test) or for administrative reasons.  
Any interruption in dosing must be documented in the subject’s electronic case report forms 
(eCRFs) and source medical record. The medical monitor/Clinical Project Manager should be 
informed as soon as possible after the decision is made to interrupt study drug for a subject. 
7.3.3. 
Treatment Compliance 
Treatment compliance will be assessed at each clinic visit through subject interview, and by 
comparing the amount of study drug that should have been taken since the last study visit with 
the amount of study drug returned. If a subject is not compliant with study drug administration, 
the investigator (in consultation with the medical monitor) will consider whether the 
noncompliance should warrant withdrawal of the subject from the study. 
7.4. 
Concomitant Medications 
Concomitant medications, including vaccinations, and any medication taken at any time 
throughout the study must be recorded in the eCRFs, along with the reason for use, dates of 
administration, dosage, frequency, and route of administration. Medication continuing from the 
previous study also must be recorded. 
7.5. 
Prohibited Medications 
Use of the following medications or treatments during this study is prohibited and will result in 
withdrawal from the study: 
• investigational/experimental therapy 
• gene therapy  
• Enzyme replacement therapy (eg, Replagal® [agalsidase alfa], Fabrazyme® 
[agalsidase beta]) 
• Glyset® (miglitol) 
• Zavesca® (miglustat) 


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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Number of Subjects 
The number of subjects to be enrolled will be dependent on the number of eligible subjects 
completing migalastat treatment in Study AT1001-020 and who consent to enroll in this 
open-label extension study.  
8.2. 
Eligibility Criteria 
Adherence to the eligibility criteria for participation in this study is essential to ensure scientific 
integrity, regulatory acceptability, and subject safety. Waivers of inclusion/exclusion criteria will 
not be granted. 
8.2.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be considered for enrollment in the study: 
1. Male or female subjects, diagnosed with Fabry disease > 12 years of age who completed 
Study AT1001-020 
2. Subject’s parent or legally authorized representative is willing and able to provide written 
informed consent and authorization for use and disclosure of personal health information 
or research-related health information, and subject provides assent, if applicable 
3. If of reproductive potential, both male and female subjects agree to use a medically 
accepted method of contraception throughout the duration of the study and for up to 
30 days after their last dose of migalastat 
8.2.2. 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from participating in the study: 
1. Subject’s last available estimated glomerular filtration rate (eGFR) in the previous study 
was < 60 mL/min/1.73 m2 
2. Subject has advanced kidney disease requiring dialysis or kidney transplantation 
3. Subject received any investigational/experimental drug, biologic, or device within 
30 days before baseline, with the exception of migalastat 
4. Subject anticipates starting gene therapy during the study period 
5. Subject has any intercurrent illness or condition at Visit 1 that may preclude the subject 
from fulfilling the protocol requirements or suggests to the investigator that the potential 
subject may have an unacceptable risk by participating in this study 
6. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other 
iminosugars (eg, miglustat, miglitol) 
7. Subject requires treatment with Replagal (agalsidase alfa) or Fabrazyme (agalsidase beta)  
8. Subject requires treatment with Glyset (miglitol) or Zavesca (miglustat) 
9. Female subject is pregnant or breast-feeding, or is planning to become pregnant during 
the study period 


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10. In the opinion of the investigator, the subject and/or parent or legally-authorized 
representative is unlikely or unable to comply with the study requirements 
8.3. 
Withdrawal Criteria 
8.3.1. 
Reasons for Discontinuation/Withdrawal 
Subjects may discontinue study drug, withdraw from the study, or be withdrawn from the study 
for any reason including, but not limited to, the following reasons:  
• at their own request or at the request of their parent or legally-authorized 
representative 
• if, in the investigator’s opinion, continuation in the study would be detrimental to the 
subject’s well-being 
• occurrence of an intolerable AE as determined by the investigator, subject, and/or 
parent or legally-authorized representative 
• failure of the subject to comply with the study visit schedule 
• persistent noncompliance, at the discretion of the investigator 
• pregnancy 
• subject becomes eligible for reimbursed product 
• inability to contact subject (ie, subject is lost to follow-up) 
• Amicus medical monitor request 
8.3.2. 
Handling of Withdrawals 
The reason for and date of discontinuation or withdrawal must be recorded in the eCRF and in 
source documents. All subjects who discontinue study treatment will be encouraged to complete 
an early termination (ET) visit and follow-up safety assessments. 
The investigator must make every effort to contact subjects who are lost to follow-up to schedule 
end-of-study assessments. Attempts to contact subjects who are lost to follow-up (eg, times and 
dates of attempted telephone contact, documentation of a registered letter) must be recorded in 
the subject’s source document.  
If a subject wishes to discontinue treatment, the investigator must determine the extent that a 
subject may be willing to continue participation in the study, as follows: 
• the parent or legally-authorized representative and/or subject wants to discontinue 
study drug, but agrees to the follow-up procedures  
• the parent or legally-authorized representative and/or subject wants to discontinue 
study drug and all follow-up procedures  
• the parent or legally-authorized representative and/or subject wants to revoke 
consent/assent to collect and use further data  


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Note: In the United States, the authorization to use and disclose data for research can 
only be revoked in writing by the subject, or parent or legally-authorized 
representative of minor subjects. 
8.4. 
Subjects of Childbearing Potential 
Female subjects of reproductive potential, and all male subjects must use a medically accepted 
contraceptive regimen during their participation in the study and for 30 days after the last dose of 
migalastat. A medically acceptable birth control method is defined as one which results in a low 
failure rate (ie, < 1% per year) when used consistently and correctly. 
A female subject is considered of reproductive potential if she has functional ovaries, ducts, and 
uterus with no impairment that would cause sterility. This includes females with oligomenorrhea 
(even severe), and females who have just begun to menstruate. 
A female is considered of non-reproductive potential if she is at least 26 weeks status-post 
documented surgical sterilization (includes hysterectomy, bilateral oophorectomy, bilateral tubal 
ligation, or salpingectomy). 
The allowed methods of contraception described in the following text are only effective when 
used consistently, correctly, and, if applicable, in accordance with the product label. The 
investigator is responsible for ensuring subjects understand how to properly use these methods of 
contraception. 
Medically acceptable methods of contraception for female subjects enrolled in the study include 
the following: 
• total abstinence, which refers to refraining from penile-vaginal intercourse, when this 
is the female’s preferred and usual lifestyle 
• hormonal contraception (ie, combination oral contraceptive pills, implant, injection, 
ring, or patch) for at least 12 weeks before baseline 
• intrauterine device that meets the < 1% failure per year rate, as stated in the product 
label, for at least 12 weeks before baseline 
• double-barrier method, defined as condom and occlusive cap (eg, diaphragm or 
cervical/vault caps) used in combination with spermicide (eg, foam, gel, film, cream, 
suppository) 
Note: The double-barrier method does not satisfy the requirements for an effective 
method of birth control in all countries and may not be utilized as a contraceptive 
method by subjects participating at sites in those countries 
Medically acceptable methods of contraception for male subjects enrolled in the study include 
the following: 
• total abstinence, which refers to refraining from penile-vaginal intercourse, when this 
is the male’s preferred and usual lifestyle 
• surgical sterilization (eg, vasectomy with documentation of azoospermia) prior to the 
subject’s entry into the study 


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Note: For this definition, “documented” refers to the outcome of the investigator’s or 
designee’s medical examination of the subject or review of the subject’s medical 
history for study eligibility, as obtained via a verbal interview with the subject or 
from the subject’s medical records. 
• double-barrier method, defined as condom and occlusive cap (eg, diaphragm or 
cervical/vault caps) used in combination with spermicide (eg, foam, gel, film, cream, 
suppository) 
Note: The double-barrier method does not satisfy the requirements for an effective 
method of birth control in all countries and may not be utilized as a contraceptive 
method by subjects participating at sites in those countries. 
Any pregnancy (in a female subject or the female partner of a male subject) occurring during the 
study must be reported as described in Section 10.5.1. 
In the event of pregnancy in a female subject, migalastat must be discontinued immediately upon 
becoming aware of the pregnancy. Female subjects or a female partner of a male subject who 
becomes pregnant during the study must be monitored by the investigator until the outcome of 
the pregnancy is known. Both the detection and the outcome of the pregnancy must be reported 
to Amicus. 
Periodic abstinence (eg, calendar, ovulation, symptom-thermal, post-ovulation methods) and 
withdrawal are not acceptable methods of contraception. 


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9. 
STUDY ASSESSMENTS AND PROCEDURES  
The schedule of study assessments and procedures is presented in Table 2. Total blood volume to 
be drawn per subject is presented in Table 3. 
All study assessments should be conducted by the investigator, and/or a suitably qualified 
designee. Information will be recorded in the source documents and, where appropriate, the 
eCRF. 
All assessments that occur during the study, where applicable and to the extent possible, should 
be completed during the designated visit, preferably in the order specified below. Once 
established, every effort should be made to maintain the order of procedures at each study visit 
throughout the study.  


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Table 2: 
Schedule of Assessments 
Assessments 
Baselinea 
Treatment Period 
EOT/ 
ET 
Follow-up 
Visit Interval 
 
Day 1 
Month  
3 
(TC) 
Month  
6 
Month  
9 
(TC) 
Month 
12 
Month 
15 
(TC) 
Month 
18 
Month 
21 
(TC) 
Month 
24 
-- 
30-Day 
Safety 
Visit Window (days) 
— 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
+6 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dosing diaryb 
X 
→ 
→ 
→ 
X 
→ 
→ 
→ 
X 
 
 
FPHPQ questionnaire 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PedsQL 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Complete physical 
examination 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, HR, RR, 
Temp) 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Body weight 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Height 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Tanner Staging 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
12-lead ECG 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Chemistry (including eGFR 
using Schwartz formula) 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Hematology 
X 
 
X 
 
X 
 
X 
 
X 
X 
 


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Table 2: 
Schedule of Assessments (Continued) 
Assessments 
Baselinea 
Treatment Period 
EOT/ 
ET 
Follow-up 
Visit Interval 
Day 1 
Month 
3 
(TC) 
Month 
6 
Month 
9 
(TC) 
Month 
12 
Month 
15 
(TC) 
Month 
18 
Month 
21 
(TC) 
Month 
24 
-- 
30-Day
Safety
Visit Window (days) 
— 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
±6 
+6
Plasma lyso-Gb3, analogs, and 
exploratory PD biomarkers 
X 
X 
X 
X 
X 
X 
Urinalysis (urine protein, 
albumin and microalbumin 
levels) 
X 
X 
X 
X 
X 
X 
Urine pregnancy test or date of 
LMP (as applicable)c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Echocardiogram (LVMi and 
additional parameters) 
X 
X 
X 
X 
Study treatment 
supply/resupply/ return 
X 
X 
X 
X 
X 
Xd 
Abbreviations: BP = blood pressure; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EOT = end of treatment; ET = early termination; 
FPHPQ = Fabry-Specific Pediatric Health and Pain Questionnaire; HR = heart rate; LMP = last menstrual period; LVMi = left ventricular mass index; 
lyso-Gb3 = globotriaosylsphingosine; PD = pharmacodynamic; PedsQL = Pediatric Quality of Life Inventory; RR = respiration rate; TC = telephone call; 
Temp = body temperature 
Note: Following Month 24, visits will continue every 6 months with interim telephone contacts at 3-month intervals. The assessment schedule will repeat starting 
from Month 3. 
Note: For the purposes of this study, a month is considered to be 30 days. 
a End of study assessments from Study AT1001-020 will be used as baseline assessments for Study AT1001-036. 
b A dosing diary will be completed throughout the treatment period. 
c Female subjects only; urine pregnancy tests will be conducted at each site visit. For menstruating females, date of LMP will be elicited during telephone 
contacts. 
d Return of study drug only. 


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Table 3: 
Total Blood Volume to be Collected (as Scheduled) per Subject per Year 
 
Blood Volume per Test (mL) 
Assessments 
Baselinea 
Month 6 
Month 12 
Total 
Chemistry 
4 
4 
4 
12 
Hematology 
2 
2 
2 
6 
Plasma lyso-Gb3 and PD 
biomarkers 
4 
4 
4 
12 
Total: 
30 mL 
Abbreviations: lyso-Gb3 = globotriaosylsphingosine; PD = pharmacodynamic 
Note: Total collection volume does not take into account additional blood samples drawn during potential 
unscheduled visits. 
a End of study laboratory assessments for Study AT1001-020 will be used as Visit 1 assessments for 
Study AT1001-036. The blood volume from baseline assessments should not be counted for subsequent years. 
9.1. 
Description of Study Visits 
9.1.1. 
Unscheduled Visits 
Unscheduled visits for medical reasons such as evaluation of AEs and/or repeat laboratory tests 
can be performed at any time at the investigator’s discretion. The date and reason for the visit, in 
addition to all information collected during the visit, should be captured in source documents and 
on the appropriate eCRFs. 
9.1.2. 
Baseline Visit 
Baseline assessments will be performed pre-dose on Day 1. Since subjects will be transitioning 
from a previous migalastat study, the final visit of that study will be utilized to satisfy any 
duplicate Visit 1 (baseline) procedures required for the current study. The desired intent is for 
treatment with migalastat to continue without a break. However, any subject who did not receive 
migalastat for more than 30 days will be required to repeat all Visit 1 procedures. 
All inclusion/exclusion criteria must be reviewed and verified at this visit to ensure that there 
have been no changes to a subject’s health that would affect that subject’s eligibility to 
participate in the study.  
9.1.3. 
Treatment Period Visits/Telephone Contacts 
Periodic visits are scheduled every 6 months during the treatment period (ie, at Months 6, 12, 
etc). Telephone contacts are scheduled at 3-month intervals in between site visits (ie, Months 3, 
9, 15, 21, etc). A month will be defined as 30 days. After the first year on study, visits will 
continue at 6-month intervals with interim telephone contact at intervening 3-month intervals. 
Following Month 24, the schedule of assessments as displayed in Table 2 will repeat starting 
with the Month 3 telephone contact (which will be Month 27). 
Telephone contacts will include questions regarding any AEs or pregnancies (ie, including delay 
in menstrual period for female subjects with regular menses) that may have occurred and any 
changes in concomitant medications. 


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9.1.4. 
Early Termination Visit 
Subjects who are withdrawn from the study should complete early termination procedures as 
soon as possible. If early termination coincides with a scheduled visit, all procedures outlined for 
the early termination visit should be performed. 
9.1.5. 
30-day Safety Follow-up Visit 
All subjects, including subjects who discontinue study drug or withdraw from the study, should 
complete a 30-day safety follow-up visit, to be scheduled at least 30 days after the last dose of 
study drug. This visit may be accomplished by a telephone contact, similar to the scheduled 
telephone contact. In these instances, in lieu of a urine pregnancy test for female subjects, 
subjects will be questioned about any pregnancies (ie, including delay in menstrual period for 
female subjects with regular menses) that may have occurred. 
9.2. 
Description of Study Assessments 
All assessments will be conducted according to the schedule presented in Table 2. Assessments 
may be repeated if requested by the medical monitor.  
9.2.1. 
Medical History 
Medical history will be collected by subject interview. Additionally, medical history deemed 
related to the subject’s Fabry disease will be identified in the subject’s medical records by the 
investigator or designee for entry into the appropriate eCRF, including, but not limited to such 
things as past serum creatinine results.  
Since subjects will have participated in a previous migalastat study, historical medical history 
(ie, events or conditions that had their onset at least 90 days prior to Visit 1) will be considered 
as medical history for this study. 
9.2.2. 
Safety Assessments 
9.2.2.1. 
Adverse Events and/or Serious Adverse Events 
Throughout the study, subjects will be given an opportunity to report AEs. The definitions, 
reporting, and monitoring of AEs and SAEs are described in Section 10. 
9.2.2.2. 
Clinical Laboratory Tests 
9.2.2.2.1. Safety Laboratory Tests 
Samples for chemistry, hematology, and urinalysis are outlined in Table 4. Laboratory samples 
collected on a dose administration day will be collected predose.  


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Table 4: 
Clinical Laboratory Parameters 
Chemistry 
Hematology 
Urinalysis 
ALT 
Hematocrit 
Color 
Alkaline phosphatase 
Hemoglobin 
Appearance 
AST 
Platelet count 
Specific gravity 
Albumin 
RBC count 
pH 
Bilirubin, total  
WBC count (absolute) 
Albumin  
BUN 
Automated WBC differential 
Bilirubin 
Calcium, total 
Basophils 
Blood 
Carbon dioxide, total (bicarbonate) 
Eosinophils 
Glucose 
Chloride 
Lymphocytes 
Ketones 
CPK 
Monocytes 
Microalbumin 
Creatinine, serum 
Neutrophils 
Microscopy of sediment 
GGT 
 
Nitrite 
Glucose 
 
Protein 
Lactate dehydrogenase  
 
WBCs 
Magnesium 
 
 
Phosphorous 
 
 
Potassium 
 
 
Protein, total 
 
 
Sodium 
 
 
Uric acid 
 
 
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase; BUN = blood urea nitrogen; 
CPK = creatine phosphokinase; GGT = gamma-glutamyltransferase; RBC = red blood cell; WBC = white blood cell 
Safety laboratory tests will be performed at a central laboratory. Instructions for the collection, 
processing, and shipment of clinical laboratory samples will be provided in the Laboratory 
Manual.  
The investigator or a designee will review laboratory results and assess any out-of-range 
laboratory results as “not clinically significant” or “clinically significant.” Any results that are 
considered clinically significant may be confirmed in a repeat test at the investigator’s discretion. 
The investigator should consider repeat testing of persistent clinically significant results until the 
analyte returns to normal levels or until an etiology is determined. The investigator or a designee 
will sign and date all laboratory reports.  
Clinically significant laboratory abnormalities must be captured as AEs or SAEs, as appropriate. 


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9.2.2.2.2. Other Laboratory Tests 
Urine pregnancy tests will be performed for all female subjects of childbearing potential (as 
defined in Section 8.4); date of last menstrual period, as applicable, will be recorded during 
telephone contacts.  
Any subject who has a positive urine pregnancy test result should have a serum pregnancy test 
performed as soon as possible for confirmation. Any subject who becomes pregnant must 
discontinue study drug. Procedures for pregnancy reporting are described in Section 10.5.1.  
9.2.2.3. 
Vital Signs 
Vital signs include blood pressure (systolic and diastolic), respiration rate, heart rate, and body 
temperature. Measurements are to be taken with the subject in a sitting or supine position after 
having rested for 5 minutes, and the same position should be used at all visits. Blood pressure 
should be obtained using the same arm for all measurements.  
9.2.2.4. 
Physical Examination 
Complete physical examinations will include assessment of head/eyes/ears/nose/throat, skin, 
thyroid, neurological system, lungs, cardiovascular system, abdomen (liver and spleen), lymph 
nodes, and extremities. 
9.2.2.5. 
Body Weight and Height 
Body weight (kg) must be measured with the subject’s shoes and clothes (except underwear) 
removed and will be rounded to 1 decimal place. The same scale should be used for individual 
subjects throughout the study and scales should be calibrated periodically throughout the study to 
ensure accuracy of measurement. 
Height (cm) must be measured with the subject’s shoes removed. 
9.2.2.6. 
Electrocardiograms 
A standard 12-lead electrocardiogram (ECG) will be performed.  
Subjects will rest for approximately 5 minutes before the ECG recording begins and will be in 
the supine position throughout the ECG evaluation. Electrocardiograms will be read centrally. 
Clinically significant findings not present before the start of treatment, which meet the definition 
of an AE, must be recorded in the eCRF. 
9.2.2.7. 
Echocardiogram 
Echocardiogram parameters considered for safety include left ventricular mass index (LVMi), 
ejection fraction, fractional shortening, left ventricular internal diameter end diastole and end 
systole, midwall fractional shortening, and wall thickness.  
Echocardiograms will be read centrally. 
9.2.2.8. 
Tanner Staging 
Tanner Staging will be performed for all subjects.  


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Because reversible infertility was noted in nonclinical studies with male rats, Tanner Staging will 
be used to assess sexual development, ie, breast development (B1 to B5) and pubic hair 
development (Ph-1 to Ph-5) in females and pubic hair and genital development (G-1 to G-5) in 
males (see Appendix A).  
9.2.2.9. 
Concomitant Medications and Procedures 
Subjects will be asked to report any new or changes in previously reported prescription and 
non-prescription medications, including dosage, frequency, and administration dates. 
Information will be entered in the eCRF and source records. Information regarding any 
procedures performed since the last visit will also be collected. 
9.2.3. 
Pharmacodynamic Assessments 
Blood samples will be collected for measurement of lyso-Gb3 levels in plasma, and analogues. In 
addition, to get a better understanding of early PD biomarkers for Fabry disease, samples may be 
used for exploratory cardiac biomarkers such as high sensitivity tropin and NT-proBRN. Plasma 
levels of lyso-Gb3 will be measured using a validated liquid chromatography mass spectrometry 
(LCMS) assay. 
9.2.4. 
Efficacy Assessments 
9.2.4.1. 
Estimated Glomerular Filtration Rate 
Estimated GFR will be calculated using the Schwartz formula according to the standards of the 
central laboratory. Subjects who reach the age of 18 and remain on study will continue to have 
eGFR calculated by this method by the sponsor at the time the value is entered into the database. 
9.2.4.2. 
Urine Protein and Albumin Levels 
Protein and albumin (or microalbumin) levels in urine (as part of urinalysis) will be measured. 
9.2.4.3. 
Echocardiogram 
The key echocardiogram parameter considered for efficacy is LVMi. In addition, ejection 
fraction, fractional shortening, left ventricular internal diameter end diastole and end systole, 
midwall fractional shortening, and wall thickness will be assessed. 
Echocardiograms will be read centrally.  
9.2.4.4. 
Subject Questionnaires 
All questionnaires will be provided in a separate Patient Outcomes Manual. 
9.2.4.4.1. Dosing Diary 
Subjects are to record the date and time of each migalastat administration in the Dosing Diary 
provided in the dosing wallet containing their study drug. Subjects will be asked to complete 
diary entries in order to track migalastat administration beginning on Day 1 and for the duration 
of the study.  


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9.2.4.4.2. Fabry-Specific Pediatric Health and Pain Questionnaire 
The Fabry-Specific Pediatric Health and Pain Questionnaire (FPHPQ) includes questions about 
Fabry disease-specific symptoms (eg, sweating, pain, dizziness and tiredness, heat and cold 
intolerance, swollen eyelids, gastrointestinal symptoms, feeling thirsty, difficulty hearing, 
ringing or buzzing noise in the ears, and ability and enjoyment to participate in sports). The 
frequency of these symptoms will be rated using a 5-point Likert scale (always, often, 
sometimes, seldom, never). Pain intensity is measured on a 10-point scale, numeric responses are 
given for onset of pain and school days missed, and yes/no questions are posed about difficulty 
hearing and other problems not specifically mentioned. There are 2 age-specific self-report 
versions for children 8 to 12 years and 13 to 18 years, respectively. 
9.2.4.4.3. Pediatric Quality of Life Inventory 
The Pediatric Quality of Life Inventory™ (PedsQL™) is a modular approach to measuring 
health-related quality of life in healthy children and adolescents and those with acute and chronic 
health conditions. It consists of 23 items and includes questions about physical functioning, 
emotional functioning, social functioning, and school functioning relative to the prior 7 days, 
using a 5-point scale. Both parents or legally-authorized representatives and subjects complete 
the appropriate version of the PedsQL independently of one another. Parents or 
legally-authorized representatives and subjects may self-administer the questions after 
introductory instructions are given by study site personnel. 


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10. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
Investigators and study site personnel are responsible for detecting, documenting, and reporting 
AEs and SAEs. For each subject, reporting of AEs and SAEs begins after written informed 
consent is provided.  
10.1. 
Definitions 
10.1.1. 
Adverse Event 
An AE is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 
symptom, or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
Therefore, AEs include the following: 
• The onset of new signs, symptoms, conditions, and illnesses 
• Exacerbation of pre-existing conditions or illnesses 
• Abnormal laboratory findings deemed clinically significant by the investigator 
• Physical examination changes deemed clinically significant by the investigator 
• Abnormal medical evaluation findings (eg, ECG) that are not documented at baseline 
and/or, in the investigator’s opinion, represent a clinically significant change in the 
subject’s health during study participation 
− Baseline medical evaluation findings (eg, ECG) that were not previously provided 
as medical history and can be determined as starting before baseline, are not 
considered AEs and will be recorded as medical history. 
Adverse events will be recorded in the eCRF and subject’s source record beginning from the 
time written consent (assent) is provided through the follow-up visit (at least 30 days after the 
last dose of study drug). 
Subjects will be enrolling in this study following completion of Study AT1001-020. Therefore: 
• Adverse events that are ongoing as of the last study visit of Study AT1001-020 will 
be entered in the AE eCRF. 
− The start date recorded in Study AT1001-020 will be the start date entered in the 
current study AE eCRF. 
− The event will be noted as continuing from Study AT1001-020 in the current 
study’s AE eCRF. 
A single diagnosis should be entered when known. If a clear diagnosis cannot be determined at 
the time of eCRF completion and the subject’s source record entry, each sign and symptom must 
be recorded individually, until a final diagnosis is established. Conditions, signs, symptoms, etc 
that are present in the subjects’ medical history at baseline should only be reported as AEs if they 
worsen (ie, increase in severity) since baseline. 


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Adverse events that begin after the first dose of investigational product in Study AT1001-036 
will be considered treatment-emergent adverse events (TEAEs).  
10.1.2. 
Serious Adverse Event 
An SAE is any AE occurring at any dose that results in any of the following outcomes:  
• death 
• a life-threatening event 
− This includes any AE that in the view of either the investigator or sponsor places 
the subject at immediate risk of death. It does not include an AE that, had it 
occurred in a more serious form, might have caused death. 
• requires inpatient hospitalization or prolongs existing hospitalization 
− Hospitalization signifies the subject has been admitted, regardless of duration, for 
observation and/or treatment that would not have been appropriate in a 
physician’s office or outpatient setting. 
− Hospitalizations for elective or pre-planned treatment of a pre-existing condition 
do not have to be reported as SAEs if the following criteria are met: 
− the condition is documented in the subject’s medical history and has not 
worsened since the informed consent form was first signed; and 
− the condition and planned procedure are documented in the subject’s source 
records at baseline. 
− Emergency room/department or outpatient treatments that do not result in 
admission do not have to be reported as an SAE, unless another SAE criterion is 
met. Events assessed and treated in these circumstances should be captured as 
AEs in the eCRF and documented in the subject’s source records. 
− Hospitalizations solely based on subject logistics (eg, subject is admitted due to 
limited hospital accessibility for what would otherwise be an out-subject 
procedure) do not have to be reported as SAEs provided that the hospitalizations 
are clearly defined as such in the subject’s source record. 
• persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• congenital anomaly/birth defect 
An important medical event that does not result in one of the above serious outcomes may be 
considered an SAE when, based upon appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the listed serious 
outcomes. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias, or convulsions that do not result 
in inpatient hospitalization, or development of drug dependency or drug abuse. 


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If the following 4 elements are known, the event must be reported as described in Section 10.4.2: 
• identifiable subject 
• event term 
• study drug 
• identifiable reporter 
Additionally, the investigator’s assessment of an event’s relationship to study drug 
(see Section 10.2) is essential for Amicus to appropriately process the report and must be 
included. 
Subjects and parents or legally-authorized representatives must be informed and understand that 
they should report events meeting the definition for SAE to study site personnel as soon as 
possible (and not wait until their next study visit). 
If a non-serious event becomes serious, the change in status must be appropriately entered in the 
eCRF and the subject’s source record, and reported to Amicus as described in Section 10.4.2. 
If the investigator becomes aware of an SAE that occurs more than 30 days after the last dose of 
study drug, and considers the event possibly, probably, or definitely related to study drug, the 
investigator should contact the medical monitor (see Table 1) or the Clinical Operations Lead to 
determine how the SAE should be documented and reported.  
10.2. 
Relationship to Study Drug 
The investigator or a medically qualified sub-investigator will review each event and assess its 
relationship to study drug based on available information and according to the following 
guidelines: 
• Definite: a reaction that follows a distinct temporal relationship from administration 
of study drug; that follows a known reaction to the agent or chemical group of the 
study drug; and that cannot be explained by the subject’s clinical state or other factors 
• Probable: a reaction that follows a reasonable temporal sequence from administration 
of study drug; that follows a known or expected response pattern to the suspected 
study drug; and that could not be reasonably explained by the known characteristics 
of the subject’s clinical state 
• Possible: a reaction that follows a reasonable temporal sequence from administration 
of study drug; that follows a known or expected response pattern to the suspected 
study drug; but that could readily have been produced by a number of other factors 
• Unlikely: a reaction that does not follow a reasonable temporal sequence from 
administration of study drug; however, causality from the study drug cannot be ruled 
out 
• Unrelated: a reaction for which sufficient data exist to indicate that the etiology is 
unrelated to study drug 


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For the purpose of expedited SAE regulatory reporting obligations (ie, to regulatory authorities 
and Institutional Review Boards [IRBs]/Independent Ethics Committees [IECs]), events assessed 
by the investigator as definitely, probably, or possibly related to study drug will be considered 
“related” to study drug (ie, associated with the use of study drug). Events assessed as unlikely or 
unrelated will be considered “not related” to study drug (ie, not associated with the use of study 
drug). 
10.3. 
Severity Assessment 
The investigator or a qualified sub-investigator will review each event and use the following 
definitions for rating intensity: 
• Mild: awareness of sign, symptom or event, but the AE is easily tolerated and does 
not interfere with daily activity 
• Moderate: discomfort enough to cause interference with usual activity and may 
warrant intervention, but the subject is still able to function 
• Severe: incapacitating with inability to do usual activities or significantly affects 
clinical status, and requires medical intervention 
It is important to distinguish the difference between events that meet the definition of serious and 
events that are deemed as severe in intensity. Adverse events assessed as severe in intensity are 
not SAEs unless at least 1 of the definitions in Section 10.1.2 is met. Adverse events of any 
intensity must be reported as SAEs if at least 1 definition in Section 10.1.2 is met.  
10.4. 
Reporting Events 
10.4.1. 
Reporting Adverse Events 
Information regarding AEs is to be obtained by questioning or examining the subject and/or 
parents or legally-authorized representatives. 
As noted in Section 10.1.1, AEs will be recorded in the eCRF and subject source record 
beginning from the time written consent (assent) is provided through the follow-up visit (at least 
30 days after the last dose of study drug). Required information will be detailed in the eCRF 
Completion Guidelines.  
10.4.2. 
Reporting Serious Adverse Events 
Serious adverse events must be documented and reported to Amicus immediately, but no later 
than within 24 hours of any knowledge by study site personnel of events. Serious adverse 
event reports must be faxed to the designated safety fax number (Table 1) to ensure appropriate 
dissemination and processing of the information. An alternate email address is provided as a 
backup, if the fax transmission is unsuccessful.  
Serious adverse event forms, which will be provided by Amicus, should be as complete as soon 
as possible, and should include all information known at the time. All relevant supporting 
documentation (eg, admission and progress notes, results of diagnostic evaluations/procedures/ 
examinations, etc) available at the time of reporting, should be included in the fax (or email, if 
necessary) along with the SAE report form. All supporting documents must be thoroughly 


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reviewed and de-identified in accordance with local data privacy regulations prior to sending to 
Amicus. The subject’s study number must be included on each page included in the faxed report 
or in the subject line of the email. Reporting timelines (as described above) must not be delayed 
while obtaining or preparing supporting information.  
If more than 1 SAE is identified in 1 subject simultaneously, separate SAE reports should be 
generated for each event. 
Information not available at the time of the initial report (eg, event end date and outcome, 
supporting documents [eg, discharge summary, etc]) must be reported to Amicus within 
24 hours of any knowledge/receipt by study site personnel of the information. Information 
must be faxed (or emailed, if necessary) to the designated safety fax number (or email address) 
(Table 1) to ensure appropriate dissemination and processing. All supporting documents must be 
thoroughly reviewed and de-identified in accordance with local data privacy regulations prior to 
sending to Amicus. The subject’s study number must be indicated on each page included in the 
fax or in the subject line of the email. 
Medical history, concomitant medication, and AE information obtained through SAE reporting 
must also be consistently recorded in the eCRF. 
10.4.3. 
Additional Reporting Requirements for Suspected Unexpected Serious Adverse 
Reaction  
The sponsor is responsible for processing suspected unexpected serious adverse reactions 
(SUSARs). SUSARs are also referred to as alert reports, expedited safety reports, and 
investigational new drug application (IND) safety reports. 
A SUSAR is defined as any SAE that is determined to be associated with the use of study drug 
and is unexpected (not currently listed in the safety reference information or is not listed at the 
specificity or severity that been observed). The sponsor will notify all investigators currently 
conducting migalastat clinical studies of all SUSARs in accordance with applicable regulations. 
SUSARs will be reported to the relevant regulatory authorities and IRBs/IECs according to the 
rules in effect in each country where study sites are located:  
• If the SUSAR is fatal or life-threatening, regulatory authorities and ethics committees 
will be notified within 7 calendar days after Amicus learns of the event.  
• If the SUSAR is not fatal or life-threatening, regulatory authorities and ethics 
committees will be notified within 15 calendar days after Amicus learns of the event. 
These notifications will need to be filed in each site’s Study File Notebook and submitted to each 
site’s IRB/IEC in accordance with policy. 
Safety updates will be provided periodically to the regulatory authorities and IRBs/IECs 
responsible for the study according to the rules in effect in each country where study sites are 
located. These updates will include information on SUSARs and other relevant safety findings. 


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10.5. 
Other Reporting Situations 
10.5.1. 
Pregnancy 
Pregnancy information for female subjects and female partners of male subjects participating in 
the study is collected by Amicus. Pregnancy, in and of itself, is not regarded as an AE (unless 
there is a suspicion that study drug may have interfered with the effectiveness of a contraceptive 
medication).  
If a female subject becomes pregnant during the course of the study, or if the female partner of a 
male subject becomes pregnant during the subject’s participation in the study, Amicus must be 
informed within 5 working days of any knowledge of the pregnancy by study site personnel. If 
an SAE occurs in conjunction with the pregnancy, the SAE must be reported as described in 
Section 10.4.2. The sponsor will provide pregnancy report forms (initial and follow-up) and 
instructions to study site personnel regarding collection of pregnancy and outcome information 
(subject to receipt of data privacy release approvals where required under local privacy laws). 
Pregnancy report forms must be faxed (or emailed, if necessary) to the designated safety fax 
number (or email) (Table 1) to ensure appropriate dissemination and processing of the 
information.  
10.5.2. 
Medication Errors, Including Overdose and Under Dose 
Medication error refers to any unintended error in the dispensing or administration of a study 
drug.  
If a subject experiences an overdose (defined as ≥ 20% higher than the assigned dose of study 
drug for that period in the protocol) or an under dose (defined as ≥ 20% lower than the assigned 
dose of study drug for that period in the protocol) during the course of the study (whether 
symptomatic or not), the Amicus’ medical monitor must be notified within 5 working days of the 
investigator or study staff first becoming aware of the overdose.  
Medication errors, including overdose and under dose, should be captured in subjects’ source 
records and recorded in the eCRFs. Any AE or SAE that occurs as a result of a medication error 
should be reported according to AE/SAE reporting requirements (see Section 10.4). 
10.5.3. 
Reporting of Possible Study Drug Product Quality Defects 
Any defect or possible defect associated with study drug must be reported to Amicus 
(clinicalcomplaints@amicusrx.com) within 1 working day of any study site personnel knowledge 
of the possible defect. The study drug and packaging components in question, if available, 
must be segregated and stored in a secure area at the site under the specified storage conditions 
(see Section 12.3.1) until it is determined whether or not the study drug and/or packaging is 
required for investigation of the possible defect. If the possible defect is associated with an SAE, 
the SAE must be reported as described in Section 10.4.2. The SAE report must include the 
possible study drug defect complaint. 


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11. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
Details of the data handling rules and statistical calculations will be provided in the statistical 
analysis plan (SAP).  
11.1. 
Endpoints 
11.1.1. 
Safety Endpoints 
Safety endpoints are as follows: 
• incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug 
• change from baseline in clinical laboratory test results over time 
• change from baseline in vital signs over time 
• change from baseline in physical examination findings over time 
• change from baseline in body weight and height over time 
• change from baseline in ECG results over time 
• change from baseline in echocardiogram parameters over time 
• change from baseline in Tanner Stage 
11.1.2. 
Pharmacodynamic Endpoints 
The PD endpoint is the change from baseline in plasma levels of lyso-Gb3. 
11.1.3. 
Efficacy Endpoints 
Efficacy endpoints are as follows: 
• change from baseline in eGFR (Schwartz formula) 
• change from baseline in urine protein and albumin levels  
• change from baseline in LVMi  
• change from baseline in FPHPQ scores  
• change from baseline in PedsQL scores 
11.2. 
Sample Size Considerations 
Since this is a long-term extension study that will enroll subjects from Study AT1001-020, no 
formal sample size calculation was performed. 


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11.3. 
Data Analysis Considerations 
11.3.1. 
Analysis Populations 
11.3.1.1. Safety Population 
The safety population will include all subjects who receive at least 1 dose or partial dose of study 
drug. All safety and PD analyses will be performed using the safety population. 
11.3.1.2. Intent-to-treat Population 
The intent-to-treat population will include all enrolled subjects. All efficacy analyses will be 
performed using intent-to-treat population. 
11.4. 
Statistical Methods 
For the purpose of statistical analyses, baseline is generally defined as the last non missing 
measurement obtained on or before the administration of the first dose of study drug. For this 
study, the baseline value for efficacy endpoints will be obtained from the baseline visit of 
Study AT1001-020. 
Only summary statistics will be provided for data collected from this study. No missing data 
imputation method is planned to handle missing data. Data will be summarized as observed. 
Data will be summarized using descriptive statistics. Continuous variables will be summarized 
by number of subjects, mean, standard deviation, median, minimum, and maximum values. 
Discrete variables will be summarized by counts and percentages.  
In general, data will be summarized by age group at baseline, by sex, and combined across all 
subjects.  
A month will be defined as 30 days. 
No missing data imputation method is planned to handle missing data. Data will be summarized 
as observed. All data will be listed. 
Full details will be presented in the SAP. 
11.4.1. 
Interim Analysis 
No interim analyses are currently planned for this study.  
11.4.2. 
Baseline Demographic and Subject Characteristics 
Baseline demographics and subjects’ characteristics will be presented for all subjects in the 
intent-to-treat and Safety Populations. Demographics will be collected from the baseline visit of 
Study AT1001-020. Age at entry into this study will be re-calculated based on the date of birth 
recorded in the Study AT1001-020. Subject characteristics will be summarized using descriptive 
statistics. 
Subject characteristics will be updated from Study AT1001-020 and will include height, body 
weight, body mass index, number of years since diagnosis of Fabry disease, previous use of 


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enzyme replacement therapy, and previous and current use of angiotensin-converting enzyme 
inhibitors, renin inhibitors, and angiotensin receptor blockers.  
11.4.3. 
Subject Disposition 
A summary of subject disposition will include number of subjects enrolled, number of subjects 
in each analysis population, number of subjects who completed the study, and number of 
subjects who did not complete the study by reason for discontinuation. 
Protocol deviations will be listed. 
11.4.4. 
Safety Analyses 
Continuous safety data will be summarized using descriptive statistics (number, mean, standard 
deviation, median, minimum, and maximum). Categorical variables will be presented by number 
(percentage). 
11.4.4.1. Exposure 
An exposure table will be presented based on subcategories as defined in the SAP. 
11.4.4.2. Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and summarized by system organ class (SOC) and preferred term.  
The number and percentage of subjects with AEs will be summarized by SOC and preferred term 
within each SOC. Additional displays will present AEs by intensity (mild, moderate, severe), 
relationship to study treatment (Related Events: definite, probable, and possible; Unrelated 
Events: unlikely and unrelated), and by outcome of events. Moreover, the number of AEs (as 
opposed to the number and percentage of subjects) will be presented. Listings will also be 
provided for SAEs and TEAEs leading to discontinuation of study treatment. 
11.4.4.3. Laboratory Data 
Actual values and changes from baseline for clinical laboratory test results will be summarized 
using descriptive statistics (number, mean, median, minimum, and maximum). Categorical 
variables will be presented by number (percentage). Shift tables will also be provided for clinical 
laboratory tests. 
Potentially clinically significant (PCS) laboratory values will be summarized by laboratory 
parameter. The PCS criteria for laboratory values will be defined in the final SAP. The summary 
will indicate the number of subjects with PCS-low or PCS-high values at any time during 
treatment with migalastat, but will not be presented by visit. It is possible for subjects to appear 
in both categories (PCS-low and PCS-high) for any parameter. The incidence rates of PCS 
values will be presented. There will be no statistical testing. 
11.4.4.4. Vital Signs 
Descriptive statistics for vital signs will be presented for systolic blood pressure, diastolic blood 
pressure, body temperature, HR, and RR, at each visit. Change from baseline to post baseline 
visit will also be presented. Data will be attributed to visits as described in the final SAP. 


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The incidence rates of PCS vital sign changes, by parameter, will be summarized. Potentially 
clinically significant criteria for vital signs are defined in the SAP. The summary will indicate 
the number and percentage of subjects with PCS-low and PCS-high values at any time during 
migalastat treatment and will not be presented by visit. It is possible for subjects to appear in 
both categories for any parameters. 
11.4.4.5. Physical Examinations 
Physical examination results will be presented for each body system/category examined; the 
number and percent of subjects judged to be normal, abnormal, or not performed will be 
summarized. Similarly, the results of the physical examinations will be summarized for subjects 
in the Safety Population who had an examination post baseline. 
Tanner Stages will be summarized using descriptive statistics. 
11.4.4.6. Electrocardiograms 
Actual values and changes from baseline for ECG parameters will be summarized using 
descriptive statistics. 
Potentially clinically significant values for quantitative ECG data will be summarized by 
parameter. The PCS criteria for 12-lead ECGs will be defined in the SAP. The summaries will 
indicate the number and percentage of subjects with PCS-low and PCS-high values at any time 
during the study, and will not be presented by visit. It is possible for subjects to appear in both 
categories for any parameters. 
Shift tables will also be provided for clinical laboratory tests and ECG results. 
11.4.4.7. Echocardiograms  
Echocardiogram parameters (other than LVMi) will be summarized using descriptive statistics. 
11.4.4.8. Concomitant Medications 
Concomitant medications include all prescription and non-prescription medicinal treatments 
(including vitamins, supplements, and vaccines) taken during the treatment period. Medications 
that are ongoing from the Study AT1001-020 or stopped within 2 weeks of the AT1001-020 
End of Study Visit, will be recorded as concomitant medications for this study. Medications from 
Study AT1001-020 that were stopped over 2 weeks prior to the start of this study will not be 
recorded as concomitant medications. Medications starting after the last dose of study drug will 
not be considered as concomitant, but will be flagged as post medications on the listing. All 
concomitant medications will be summarized. 
Concomitant medications will be coded using the World Health Organization (WHO) Drug 
Dictionary and summarized according to the generic terms and ATC codes (Anatomical 
therapeutic chemical [classification system]). Medications will be tabulated in decreasing order 
of the total number of subjects who took each medication. In addition, the total number of 
subjects to ever take any concomitant medication will be presented. 


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11.4.5. 
Pharmacodynamic Analyses 
Continuous plasma lyso-Gb3 levels will be summarized using descriptive statistics. Lyso-Gb3 
analogues and exploratory cardiac biomarkers, if analyzed, will also be summarized using 
descriptive statistics. 
11.4.6. 
Efficacy Analyses 
Actual values and changes from baseline (as applicable) in eGFR, urine levels of protein and 
albumin, LVMi, FPHPQ scores, and PedsQL scores will be summarized using descriptive 
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12. 
STUDY TREATMENTS 
12.1. 
Description of Study Drug 
Migalastat is an iminosugar that functions as a selective pharmacological chaperone. Migalastat 
will be supplied as a gelatin capsule (Table 5). Migalastat capsules must be swallowed whole and 
must not be cut, crushed, or chewed. 
Table 5: 
Investigational Product (Capsule) 
 
Investigational Product 
Product Name 
Migalastat 
Dosage Form 
Capsule 
Unit Dose 
123 mg (equivalent to 150 mg migalastat HCl) 
Excipients 
Pregelatinized starch, magnesium stearate 
Route of Administration 
Oral 
Physical Description 
White opaque/blue opaque, hard gelatin capsules (size “2”), 
printed with an identifying code "SGXXX" or “A1001” and 
supplied in blister packs 
Manufacturer 
Almac Pharma Services Limited 
Seagoe Industrial Estate 
Portadown 
Craigavon 
County Armagh 
BT63 5UA United Kingdom 
Abbreviation: HCl = hydrochloride 
12.2. 
Packaging and Labeling 
Migalastat HCl 150-mg oral capsules will be supplied by Amicus as hard gelatin capsules in 
blister packs.  
Each container will be labeled in conformance with regulatory requirements and where 
applicable, local laws. All labels will be printed with the following information at a minimum: 
study identifier, identity of drug and dosage, sponsor name and contact details (and/or details of 
a local designee contact), dosing instructions, storage information, and other applicable local law 
statements.  
12.3. 
Study Drug Accountability 
In accordance with local regulatory requirements, the investigator or designee must document 
the amount of investigational product dispensed and/or administered to study subjects, the 
amount returned by study subjects, and the amount received from and returned to Amicus 
(or designee). Product accountability records must be maintained throughout the study. 
Subjects will be instructed to return all unused, partially used, or empty study drug containers at 
each specified visit. 


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The study monitor will periodically check the supplies of study drugs held at the site to verify 
accountability of all study drugs used and to verify that the drug accountability logs are 
completed and maintained in the investigator study file. When instructed by the study monitor, 
the investigator will return all original containers of study drugs, whether empty, or containing 
used or unused study drugs to Amicus or designee for destruction. Sites may not destroy study 
drugs on site unless Amicus has provided prior written approval. 
12.3.1. 
Handling, Storage, Return, and Disposal of Study Drugs 
Sites will be instructed to store migalastat capsules at room temperature (15°C to 25°C/59°F to 
77°F) with excursions permitted to 30°C/86°F in a secure area with temperature monitoring, free 
from environmental extremes, and with restricted access.  
A temperature log must be maintained for the duration of the study, and the temperature of the 
storage room (or cabinet) in which the study drugs are stored must be recorded for each working 
day of the week that pharmacy staff (or designated study staff) is available. Temperature is 
required to be recorded using a standard Min-Max Thermometer that has calibration records 
available (details usually contained within the device leaflet) and is maintained according to 
institutions standard maintenance policy. 
The study drug is to be stored only at the site listed on the US Food and Drug Administration 
(FDA) Form 1572. Study drug is to be dispensed only to subjects from/for whom written 
informed consent/assent has been obtained, have met all entry criteria, and are assigned subject 
numbers. 
12.3.2. 
Shipment, Return, and Disposal of Investigational Product 
The investigator (or designee) will inventory and acknowledge receipt of all shipments of 
investigational product. 


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13. 
STUDY MANAGEMENT 
13.1. 
Documentation of Protocol-required Information and Study 
Findings 
For this study, eCRFs with remote electronic data capture (EDC) provided through a qualified 
third party vendor will be used. The data will be entered on the eCRFs in a timely manner on an 
ongoing basis as defined in the Data Management Plan. The investigator, or designated 
representative, should complete the eCRF pages as soon as possible after information is 
collected, preferably on the same day that the subject is seen for an examination, treatment, or 
any other study procedure. Any outstanding entries must be completed immediately after the 
final examination. All data must be documented separately in source records. An explanation 
should be given for all missing data. 
Details of eCRF completion and correction will be explained to the investigator. The investigator 
is responsible for ensuring that data are properly recorded on each subject’s eCRFs and related 
documents. If the investigator authorizes other persons to make entries onto the eCRFs, the 
names, positions, signatures, and initials of these persons must be documented in writing and 
supplied to Amicus.  
The completed eCRFs must be reviewed and electronically signed by the investigator who 
signed the study protocol signature page to ensure that the observations and findings are recorded 
on the eCRFs correctly and completely. 
At the end of the study, eCRFs (including queries and audit trails) will be retained by Amicus 
and copies will be sent to the investigator to maintain as the investigator’s copy. 
13.2. 
Data Management 
Only data specified in the protocol will be collected as part of this study. All eCRF data will be 
entered into the EDC system and managed by a contract research organization (CRO). 
Additional protocol-specified data, such as laboratory and ECG data, may be collected through 
third party vendors and integrated with eCRF data by the CRO to create complete datasets for 
analysis. All protocol-specified data will be transmitted electronically to Amicus (or the CRO). 
Management of clinical data will be performed in accordance with applicable standards and data 
cleaning procedures as defined in the Data Management Plan to ensure the integrity of the data 
(eg, determining errors and inconsistencies in the data, and ensuring data are corrected by study 
site personnel or designees).  
After database lock, each site will receive their site-specific eCRF data as entered into the EDC 
system for the study in a secure electronic format, including full discrepancy and audit history. 
Additionally, an electronic copy of all data from the study collected at that study center will be 
retained by Amicus (or designee) for storage. 
13.3. 
Study Monitoring, Source Data Verification, and Onsite Audits 
Monitoring and auditing procedures developed or endorsed by Amicus will be followed, in 
compliance with Good Clinical Practice (GCP). Direct access to the onsite study documentation 
and source documents must be ensured by the investigator. 


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Monitoring will be performed by personal visits from a sponsor representative (ie, study 
monitor) who will check the eCRFs for completeness and clarity, and crosscheck them with 
source documents (see essential documents, Section 13.5). In addition to the monitoring visits, 
frequent communications (eg, letter, e-mail, telephone, and fax) by the study monitor will ensure 
that the study is conducted according to the protocol design and regulatory requirements. 
Domestic and foreign regulatory authorities, the IRB/IEC, and/or an auditor authorized by 
Amicus may request access to all source documents, eCRFs, and other study-related 
documentations for onsite audit or inspection. Direct access to these documents must be 
guaranteed by the investigator, who must provide support at all times for these activities. 
Medical records and other study documents may be copied during audit or inspection provided 
that subject names, family member names, telephone numbers, and addresses are obliterated on 
the copies to ensure confidentiality. 
The investigator should contact Amicus immediately if contacted by a regulatory authority 
regarding an inspection or audit. 
13.4. 
Study Site Closure 
Upon completion or termination of the study, the study monitor will conduct site closure 
activities with the investigator or site staff (as appropriate), in accordance with applicable 
regulations, GCP, and Amicus or its designee’s Standard Operating Procedures. Amicus or the 
investigator has the right to close any study site at any time. The reason(s) for closure will be 
documented in writing. To the extent possible, premature closure would occur after mutual 
consultation. Completion or premature termination of the study will be reported by Amicus to 
the regulatory agency and by Amicus or investigator to the IRB/IEC as required by the IRB/IEC 
or by local regulation. Study materials must be returned, disposed of, or retained as directed by 
Amicus 
13.5. 
Records Retention 
The investigator must obtain approval in writing from Amicus before destruction of any records. 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or at least 2 years have elapsed since the formal discontinuation of 
clinical development of migalastat. However, because of international regulatory requirements or 
country-specific requirements, Amicus may request retention for a longer period. 
Prior to any decision regarding the disposal or destruction of study documents, the investigator 
should contact Amicus. The sponsor may request that the site take alternative actions other than 
disposal or destruction of study documents. 
Essential documents include the following: 
• Signed informed consent/assent documents for all subjects, including all informed 
consent forms completed following any protocol amendment 


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• Subject identification code list and enrollment log 
Note: European Union (EU) legislation requires this list to be maintained for a 
minimum of 15 years. 
• Composition of the IEC/IRB and record of all communications between the 
investigator and IEC/IRB as well as between the investigator and Amicus or CRO 
• A list of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study and their signatures 
• Copies of eCRFs/diaries and documentation of corrections for all subjects 
• Investigational product accountability records 
• Record of any body fluids or tissue samples retained 
• All other source documents (eg, subject medical records, hospital records, laboratory 
records, etc) 
• All other documents as listed in Section 8 of the ICH GCP E6 guidelines 
(ie, Essential Documents for the Conduct of a Clinical Trial) 
Normally, these records will be held in the investigator’s archives. If investigators are unable to 
meet this obligation, they must ask Amicus for permission to make alternative arrangements. 
Details of these arrangements must be documented in writing. 
13.6. 
Use of Study Findings 
All information concerning migalastat as well as any matter concerning the operation of Amicus, 
such as clinical indications for migalastat, its formula, methods of manufacture, and other 
scientific data relating to it, that has been provided by Amicus and are unpublished, are 
confidential and must remain the sole property of sponsor. The investigator will agree to use the 
information only for the purposes of carrying out this study and for no other purpose unless prior 
written permission from Amicus is obtained. 
Amicus has full ownership of the data collected as part of the study. 
By signing the clinical study protocol and the confidentiality agreement, the investigator agrees 
that the results of the study may be used for the purposes of national and international 
registration, publication, and information for medical and pharmaceutical professionals. 
Regulatory authorities will be notified of the investigator’s name, address, qualifications, and 
extent of involvement. 
Amicus will ensure that a final report on the study is prepared with study findings are reported in 
a manner that complies with applicable requirements for reporting clinical study results. 
As required by local regulation or by the IEC/IRB, a summary of the study will be submitted by 
Amicus to the regulatory authorities and by the investigator to the IEC/IRB. 


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14. 
STUDY CONDUCT CONSIDERATIONS 
This global study will include both IND (US) and non-IND (foreign) sites. All investigators will 
be required to certify their compliance with both ICH E6 GCP and their respective country’s 
applicable laws and regulations. Both IND and non-IND sites will be operating under a single 
protocol (ie, there will not be a separate protocol for non-IND sites). The sponsor will ensure that 
the conduct, monitoring, auditing, recording, analysis, and reporting of clinical trial results are in 
accordance with ICH GCP, providing assurance that the data and reported results are credible 
and accurate and that the rights, safety, and well-being of trial subjects are protected. 
14.1. 
Regulatory and Ethical Considerations 
This study is to be conducted according to globally accepted standards of GCP (as defined in the 
ICH GCP E6 guidelines), in agreement with the ethical principles outlined in the current version 
of Declaration of Helsinki, and in keeping with local country-specific regulations, including, but 
not limited to: 
• IRB/IEC review and favorable opinion/approval of study protocol and any subsequent 
amendments 
• Subject informed consent 
• Investigator reporting requirements 
14.1.1. 
Independent Ethics Committees/Institutional Review Boards/Research Ethics 
Boards Approval and Study Compliance 
Prior to initiation of a study site, Amicus will obtain appropriate favorable opinions/approvals to 
conduct the study in accordance with ICH GCP and applicable country-specific regulatory 
requirements. 
14.1.2. 
Informed Consent/Assent Information 
Signed written informed consent/assent is to be obtained for each subject prior to enrollment into 
the study and any study-related assessments being performed. If the subject is under the legal age 
of consent, the consent form must be signed by the subject’s parent or legally-authorized 
representative in accordance with the relevant country and local regulatory requirements. The 
document must be in a language understandable to the subject and/or the subject’s parent or 
legally-authorized representative and must specify who informed the subject and/or the subject’s 
parent or legally authorized representative. Where required by local law, the person who informs 
the subject must be a physician. 
The subject and/or subject’s parent or legally-authorized representative must be provided the 
opportunity to read the informed consent/assent document and have all their questions and 
concerns addressed before giving consent/assent in writing. If the subject and/or subject’s parent 
or legally-authorized representative is unable to read, oral presentation and explanation of the 
written informed consent/assent form and information to be supplied to the subject must take 
place in the presence of an impartial witness. Details about why oral presentation was used, how 
the information was presented, and how the subject provided consent must be described in the 
source documentation. 


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The subject’s consent/assent must be confirmed at the time of consent/assent by the personally 
dated signature (or thumbprint or mark) of the subject and parent or subject’s legally-authorized 
representative and by the personally dated signature of the person conducting the informed 
consent discussions. A copy of the signed informed consent/assent form will be given to the 
subject and the original will be retained by the site. An entry must be made in the subject’s dated 
source documents to confirm that informed consent/assent was obtained prior to any 
study-related procedures and that the subject received a copy of the signed informed 
consent/assent. 
The witness and the person conducting the informed consent/assent discussions must also sign 
and personally date the consent/assent document. Until a signed written consent/assent has been 
obtained, the investigator will not perform any measures specifically required for this study. 
The investigator must inform the subject’s primary physician about the subject’s participation in 
the study if the subject has a primary physician and if the subject agrees to the primary physician 
being informed. 
14.1.3. 
Ongoing Information for Independent Ethics Committee/Institutional Review 
Board  
The information listed below must be submitted to IECs/IRBs according to timelines specified 
by individual IEC/IRB documented submission policies and procedures, or by local law. 
Submissions may be made by Amicus (or designee) or by the investigator. The parties 
responsible for submissions will be identified and documented prior to shipment of 
investigational product. 
• Information on AEs and SAEs 
• Expedited safety reports 
• Periodic reports on the progress of the study 
• Revised informed consent forms 
• Amendments to the protocol 
• Updated Investigator’s Brochure 
14.1.4. 
Posting of Information on Publicly Available Clinical Trial Registers 
The sponsor will be responsible for registering this study in a public registry that meets the 
requirements specified by the International Council of Medical Journal Editors, such as 
ClinicalTrials.gov and Eudra CT for publication of study results. Investigators contact 
information will be included in the study listing. 
14.1.5. 
Quality Control 
In accordance with applicable regulations, GCP, and sponsor procedures, Amicus or its designee 
will contact the site prior to the start of the study to review with the study site personnel the 
protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and 
Amicus’s or its designee’s requirements. When reviewing data collection procedures, the 


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discussion will include identification, agreement, and documentation of data items that will be 
recorded in the eCRF and requirements for source documentation. 
The sponsor or its designee will monitor the study to ensure the following: 
• data are authentic, accurate, and complete 
• safety and rights of subjects are being protected 
• study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements 
The investigator and the head of the medical institution (where applicable) agrees to allow the 
monitor direct access to all relevant documents. 
14.1.6. 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, Amicus may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
authorities may conduct a regulatory inspection at any time during or after completion of the 
study. In the event of an assessment, audit or inspection, the investigator (and medical 
institution) must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the conduct of 
the study, any findings/relevant issues and to implement any corrective, and/or preventative 
actions to address any findings/issues identified during the regulatory audit or inspection. 
14.1.7. 
Confidentiality 
Subject names (and the names of family members, telephone numbers, and addresses) will not be 
supplied to Amicus. A unique subject number will be recorded in the eCRF, and if the subject 
name appears on any other document (eg, laboratory report), it must be obliterated on the copy of 
the document to be supplied to Amicus. Study findings stored on a computer will be stored in 
accordance with local data protection laws (eg, EU Directive 95/46/EC, EU Directive 94/45/EC, 
and the General Data Protection Regulation (EU) 2016/679). The subject and the subject’s parent 
or legally-authorized representative will be informed that representatives of Amicus, IEC/IRB, or 
regulatory authorities may inspect their medical records to verify the information collected, and 
that all personal information made available for inspection will be handled in strictest confidence 
and in accordance with local data protection laws. 
The investigator will maintain a personal subject identification list (subject numbers with the 
corresponding subject names) to enable records to be identified. 
14.1.8. 
Protocols Amendments and Deviations 
Any non-administrative changes to the protocol, initiated either by Amicus or by the 
investigator, will require a formal amendment procedure. Approval of all amendments must be 
obtained from Amicus, relevant IEC/IRB, and regulatory authorities (in accordance with local 
requirements) prior to implementation.  
If a clarification on a procedure or an error is found in the protocol, a protocol clarification 
memo may be sent to all sites and the IRB/IEC before an amendment is issued. 


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Changes to the administrative aspects of the study will not require formal protocol amendments 
or IEC/IRB approval, but can be treated as administrative amendments. However, the IEC/IRB 
should be kept informed of such changes. Changes in study staffing or contact information are 
examples of administrative changes not requiring formal protocol amendments. 
Protocol deviations to eligibility criteria, addition or deletion of tests, dosing, duration of 
treatment, and/or any other aspect of the study design that may significantly impact subject 
safety or scientific integrity, are not permitted under GCP or by Amicus, unless necessary to 
eliminate an immediate hazard to the subject(s). Where Amicus and/or investigator must take 
urgent safety measures to protect the subjects from an immediate hazard, a protocol deviation 
may be allowed prior to obtaining approval from the relevant IEC/IRB (and/or regulatory 
authorities) according to the US CFR Title 21 Part 312.30(b)(2). In such cases, Amicus and the 
IEC/IRB must be notified within 1 business day. 
Amicus and the relevant IEC/IRB, where required by local law, must be informed of all protocol 
deviations and violations and the investigators will document such protocol deviations and 
violations in subject source documents and eCRFs. 
14.1.9. 
Delegation of Investigator Duties 
The investigator must ensure that all persons assisting with this study are adequately qualified 
and informed about their study-related duties and functions, the protocol and any amendments to 
the protocol, and the study treatment. 
Investigators must maintain a list of sub-investigators and other appropriately qualified persons 
to whom they delegate significant study-related duties. 
Should the investigator delegate the supervision of the administration of the study drugs to a 
designated person, the designee should have the appropriate medical qualifications to effectively 
conduct or supervise any potential resuscitation procedures. 
14.2. 
Legal and Financial Aspects 
14.2.1. 
Liability and Insurance 
Liability and insurance provisions for this study are given in separate agreements. 
14.2.2. 
Financial Disclosure 
Before the start of the study, the investigator will disclose to Amicus any proprietary or financial 
interests he or she might hold in the investigational products, migalastat, or Amicus as required 
by CFR Title 21 Part 54 and outlined in the financial disclosure form provided by Amicus. The 
investigator agrees to update this information in case of significant changes during the study and 
within 1 year of its completion. The investigator also agrees that, where required by law or 
regulation, Amicus may submit this financial information to domestic or foreign regulatory 
authorities in applications for marketing authorizations. 
Where required by regulation:  
• The investigator will disclose his/her financial interests to the subjects in the informed 
consent information. 


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• The investigator or Amicus, on behalf of the investigator, will submit the financial 
arrangements for the study to the regulatory authorities or to the IRB/IEC.  
Financial disclosures will also be provided by each sub-investigator to whom the investigator 
delegates significant study-related responsibilities. 


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15. 
REFERENCES 
Beck MJ, Padgett EL, Bowman CJ, Wilson DT, Kaufman LE, Varsho BJ, et al. (2006). 
Nonclinical juvenile toxicity testing. In Hood RD, ed. Developmental and Reproductive 
Toxicology, CRC Press. 
Benjamin ER, Flanagan JJ, Schilling A, Chang HH, Agarwal L, Katz E et al. (2009). The 
pharmacological chaperone 1-deoxygalactonojirimycin increases α-galactosidase A levels in 
Fabry patient cell lines. Journal of Inherited Metabolic Disease. 32:424-440. 
Benjamin, ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, et al. (2017). The validation of 
pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genetics 
in Medicine. 19(4): 430-438. 
Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. (1967). Enzymatic 
defect in Fabry’s disease: ceramidetrihexosidase deficiency. New England Journal of Medicine. 
276:1163-1167. 
Desnick RJ, Ioannou YA, Eng CM. (2001). α-Galactosidase A deficiency: Fabry disease. In 
Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited 
Disease. New York: McGraw-Hill. 
Desnick RJ, Schindler D. (2001). α-N-aceytylgalactosaminidase deficiency: Schindler disease. 
McGraw-Hill. Accessed May 9, 2006. www.ommbid.com. 
Eurordis. (2005). ECRD Report 2005. In European Conference on Rare Diseases. Luxemborg: 
Eurordis. 
Fan JQ, Ishii S, Asano N, Suzuki Y. (1999). Accelerated transport and maturation of lysosomal 
α-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nature Medicine. 5:112-115. 
Filoni C, Caciotti A, Carraresi L, Cavicchi C, Parini R, Antuzzi D et al. (2010). Functional 
studies of new GLA gene mutations leading to conformational Fabry disease. Biochimica et 
Biophysica Acta. 1802:247-252. 
Gal A, Schäfer E, Rohard I. (2006). The genetic basis of Fabry disease. In Mehta A, Beck M, 
Sunder-Plassmann G, eds. Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford 
PharmaGenesis. 
Germain DP. (2010). Fabry disease. Orphanet Journal of Rare Diseases. 5:30. 
Germain DP, Shabbeer J, Cotigny S, Desnick RJ. (2002). Fabry disease: twenty novel 
α-galactosidase A mutations and genotype-phenotype correlations in classical and variant 
phenotypes. Molecular Medicine. 8:306-312. 
Hopkin RJ, Bissler J, Banikazemi M, Clarke L, Eng CM, Germain DP, Lemay R, 
Tylki-Szymanska A, Wilcox WR. (2008). Characterization of Fabry disease in 352 pediatric 
patients in the Fabry registry. Pediatric Research. 64:550-555. 
Hopkin RJ, Jefferies JL, Laney DA, Lawson VH, Mauer M, Taylor MR, Wilcox WR, on behalf 
of the Fabry Pediatric Expert Panel. (2016). The management and treatment of children with 
Fabry disease: a United States-based perspective. Molecular Genetics and Metabolism. 
117:104-113. 


Amicus Therapeutics 
 
Protocol AT1001-036 
Amendment 2 
19 August 2021 
Page 57 of 60 
Confidential 
Ishii S, Chang HH, Kawasaki K, Yasuda K, Wu HL, Garman SC, Fan JQ. (2007). Mutant 
α-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: 
biochemical characterization and restoration of normal intracellular processing by 
1-deoxygalactonojirimycin. Biochemical Journal. 406:285-295. 
Johnson FK, Mudd PN Jr, Janmohamed SG. (2015). Relative bioavailability and the effect of 
meal type and timing on the pharmacokinetics of migalastat in healthy volunteers. Clinical 
Pharmacology in Drug Development. 4(3):193-202. 
Mechtler TP, Stary S, Metz TF, De Jesús VR, Greber-Platzer S, Pollak A et al. (2012). Neonatal 
screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in 
Austria. The Lancet. 379:335-341. 
Meikle PJ, Hopwood JJ, Clague AE, Carey WF. (1999). Prevalence of lysosomal storage 
disorders. Journal of the American Medical Association. 281:249-254. 
Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, 
Widmer U, Beck M, on behalf of the FOS European Investigators. (2006). Clinical 
manifestations of Fabry disease in children: data from the Fabry Outcome Survey. 
Acta Pædiatrica. 95:86-92. 
Shabbeer J, Yasuda M, Benson SD, Desnick RJ. (2006). Fabry disease: identification of 50 novel 
α-galactosidase A mutations causing the classic phenotype and three-dimensional structural 
analysis of 29 missense mutations. Human Genomics. 2:297-309. 
Shabbeer J, Yasuda M, Luca E, Desnick RJ. (2002). Fabry disease: 45 novel mutations in the 
α-galactosidase A gene causing the classical phenotype. Molecular Genetics and Metabolism. 
76:23-30. 
Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H et al. (2006). High 
incidence of later-onset Fabry disease revealed by newborn screening. American Journal of 
Human Genetics. 79:31-40. 
Topaloglu AK, Ashley GA, Tong B, Shabbeer J, Astrin KH, Eng CM et al. (1999). Twenty novel 
mutations in the α-galactosidase A gene causing Fabry disease. Molecular Medicine. 5:806-811. 
Yam GH, Bosshard N, Zuber C, Steinmann B, Roth J. (2006). Pharmacological chaperone 
corrects lysosomal storage in Fabry disease caused by trafficking-incompetent variants. 
American Journal of Physiology - Cell Physiology. 290:C1076-1082. 
Yam GH, Zuber C, Roth J. (2005). A synthetic chaperone corrects the trafficking defect and 
disease phenotype in a protein misfolding disorder. FASEB Journal. 19:12-18. 
Zavesca Package Insert (2017). miglustat capsules, 100mg. South San Francisco, CA, Actelion 
Pharmaceuticals US Inc. 


Amicus Therapeutics 
 
Protocol AT1001-036 
Amendment 2 
19 August 2021 
Page 58 of 60 
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16. 
APPENDICES 
APPENDIX A. TANNER STAGING 
Provided by Endotext 
Beccuti G and Ghizzoni L. Normal and Abnormal Puberty. In: De Groot LJ, Chrousos G, 
Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, 
New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth 
(MA): MDText.com, Inc.; 2000- 2015 Aug 8. PMID: 25905253 


Amicus Therapeutics 
 
Protocol AT1001-036 
Amendment 2 
19 August 2021 
Page 59 of 60 
Confidential 
 
Figure 1. (Left) Stages of breast fB) development. B-1: pre-pubertal; B -2: breast bud; B-3: 
enlargement of beast and areola Wth no separation of the contours; B-4: projection of 
areola and papilla to form a secondary mound above the level of the breast; B-5: recession 
of the areola to the general contour of the breast \11.oith projection of the papilla only. (Right) 
Stagesofpubic hairfPhJ development in females. Ph-1: pre-pubertal; Ph-2: sparse groWh 
of long slightly pigmented hair usually slightly rurlymainlyalong the labia; Ph-3: the hair is 
darker, coarser, and curlier and spreads over the junction of the pubes; Ph-4: the hair 
spreads covering the pubes; Ph-5: the hair extends to them edial surface of the thighs and 
is distributed as an inverse triangle. 


Amicus Therapeutics 
 
Protocol AT1001-036 
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Confidential 
 
fi~re 2. Stages of genital fG) and pubic hair (Ph) development in the male. G-1, Ph-1: 
pre-pubertal; G-2: the testis and scrotum enlarge, and the skin of the scrotum shovvssome 
reddening and change in the texture. Sparse gro\11.th of pigmented hair usually slightly a.u1y, 
mainly at the base of the penis(Ph-2); G-3: Testis and scrotum enlarge further, the penis 
gro....vs mainly in length but also in breadth. The hair is darker, coarser and rurlier and 
spreads overt he junction of the pubes (Ph-3); G-4: Scrotum, testis, and penis grow further 
\J\tth development of the glans, and further darkening of the scrotal skin. The hair spreads 
covering the pubes; G-5: adult stage Wth spreading of the hair to the medial surlace of the 
thighs (P h-5). 

SAP_001.pdf: 
Official Title: 
Statistical Analysis Plan: A Long-Term, Open-Label 
Study to Evaluate the Safety, Pharmacodynamics, and 
Efficacy of Migalastat In Subjects > 12 Years of Age 
with Fabry Disease and Amenable GLA Variants 
 
 
NCT Number: 
NCT04049760 
 
 
Document Date:  
06 October 2021 
 


Statistical Analysis Plan for Interventional Studies 
Sponsor: Amicus Therapeutics; Protocol No.: AT1001-036 
 
This document is confidential. 
SAP Version: Final 1.0 
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Statistical Analysis Plan 
 
Study Drug: 
Migalastat Hydrochloride 
 
Protocol Number: AT1001-036 
 
Study Title:  
A Long-term, Open-label Study to Evaluate the Safety, Pharmacodynamics, and Efficacy of Migalastat in 
Subjects > 12 Years of Age With Fabry Disease and Amenable GLA Variants 
 
Version: 1.0 
 
Date: 06Oct2021 
 
Based on: Protocol Amendment 2 (19Aug2021)  
 
 
Sponsor:   
Amicus Therapeutics, Inc. 
 
 
3675 Market Street 
Philadelphia, PA 19104 
Phone: +1-609-662-2000 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notice of Confidential and Proprietary Information: 
The information in this document is the property of Amicus Therapeutics and is strictly confidential. 
Neither the document nor the information contained herein may be reproduced or disclosed outside of 
Amicus Therapeutics without the prior written consent of the company, except to the extent required 
under applicable laws or regulations. 


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SAP Version: Final 1.0 
Controlled Document ID: 3903A.00, Effective Date 30Apr2018 
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Revision History 
Version # 
Date (DDMmmYYYY) 
Document Owner 
Revision Summary 
1.0 
06oct2021 
 
Initial Release Version 
 
PPD


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I confirm that I have reviewed this document and agree with the content.
Approvals
Syneos Health Approval
Name, Title
Lead Biostatistician
Signature
Date (DD-Mmm-
YYYY)
Name, Title
Senior Reviewer
Signature
Date (DD-Mmm-
YYYY)
Amicus Therapeutics Approval
Name, Title
Sponsor Contact
Signature
Date (DD-Mmm-
YYYY)
PPD
PPD
PPD


Statistical Analysis Plan for Interventional Studies
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Table of Contents
Revision History..........................................................................................................................2
Approvals ..................................................................................................................................3
Glossary of Abbreviations...................................................................................................7
Introduction ........................................................................................................................9
Study Objectives and Endpoints.......................................................................................10
Study Design....................................................................................................................12
Analysis Population..........................................................................................................15
General Aspects for Statistical Analysis ...........................................................................16


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Demographic, Other Baseline Characteristics and Medication .........................................20
Efficacy ............................................................................................................................22
Analysis of Pharmacodynamics........................................................................................24
Safety...............................................................................................................................25


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Reference List..................................................................................................................29
Interim Analyses...............................................................................................................30
Changes from Analysis Planned in Protocol.....................................................................31
Programming Considerations ...........................................................................................32
Quality Control .................................................................................................................37


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Glossary of Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
AE
Adverse Event
ATC
Anatomical Therapeutic Chemical
BMI
Body Mass Index
CDISC
Clinical Data Interchange Standards Consortium
cm
Centimeters
CSR
Clinical Study Report
ECG
Electrocardiogram
ECHO
Echocardiogram
eCRF
Electronic Case Report Form
eGFR
Estimated Glomerular Filtration Rate
ERT
Enzyme Replacement Therapy
EOT
End of Treatment
ET
Early Termination
FPHPQ
Fabry-Specific Pediatric Health and Pain Questionnaire
GLA
-Galactosidase A
HEENT
Head, Eyes, Ears, Neck and Throat
ICF
Informed Consent
ICH
International Conference on Harmonisation
LVMI
Left Ventricular Mass Index
lyso-Gb3
Globotriaosylsphingosine
MedDRA
Medical Dictionary for Regulatory Activities
PCS
Potentially Clinically Significant
PD
Pharmacodynamics
PR
PR Interval
PT
Preferred Term
QOD
Every other day
QRS
QRS Complex
QT
QT Interval


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Abbreviation 
Description 
QTc 
Corrected QT Interval 
QTcB 
Corrected QT Interval with Bazett's Formula 
QTcF 
Corrected QT Interval with Fridericia's Formula 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS® 
Statistical Analysis System 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SI 
Système International 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-Emergent Adverse Event 
TLF 
Tables, Listings and Figures 
WHO-DD 
World Health Organization Drug Dictionary (WHO Drug Enhanced + 
Herbal B3 March 2018 or latest available version) 
 


Statistical Analysis Plan for Interventional Studies
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Introduction
The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary tables and 
figures which will be produced, and the statistical methodologies that will be used, are complete and 
appropriate to allow valid conclusions regarding the study objectives.
This SAP is created based on Protocol AT1001-036, Amendment 2, 19Aug2021. The purpose of this SAP
is to outline the planned analyses by Syneos Health to support the completion of the Clinical Study 
Report (CSR). This SAP describes in detail the statistical methodology and the statistical analyses to be 
conducted for the above-mentioned protocol. The planned analyses identified in this SAP are following 
the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (ICH) guidelines E9 (R1) Statistical Principles for Clinical Trials. They will be included in regulatory 
submissions and/or future manuscripts.
Responsibilities
Syneos Health will perform the statistical analyses and is responsible for the production and quality 
control of all SDTMs, derived datasets, and tables, listings, and figures (TLFs). 
Timing of Analyses
The primary analysis of safety and efficacy and/or pharmacodynamics is planned after all subjects 
complete the final study visit or terminate early from the study. Unless otherwise specified, the analysis 
includes all data collected in the database through the time of the database lock.


Statistical Analysis Plan for Interventional Studies
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Study Objectives and Endpoints
Study Objectives
Primary Objective
The primary objective of this study is as follows:
to assess the long-term safety of migalastat treatment in pediatric subjects diagnosed with Fabry 
-Galactosidase A (GLA) amenable to 
treatment with migalastat
Secondary Objectives
The secondary objectives of this study are as follows:
to characterize the pharmacodynamics (PD) of migalastat in pediatric subjects diagnosed with 
Fabry disease and who have GLA variants amenable to treatment with migalastat 
to assess the efficacy of migalastat in pediatric subjects diagnosed with Fabry disease and who 
have GLA variants amenable to treatment with migalastat.
Study Endpoints
Efficacy Endpoints
The efficacy endpoints of this study are as follows:
change from baseline in estimated glomerular filtration rate (eGFR; Schwartz formula)
change from baseline in urine protein and albumin levels
change from baseline in left ventricular mass index (LVMi)
change from baseline in Fabry-Specific Pediatric Health and Pain Questionnaire (FPHPQ) scores
TM)
Pharmacodynamic Endpoints
The PD endpoint of this study is the change from baseline in plasma levels of Globotriaosylsphingosine 
(lyso-Gb3).
Safety Endpoints
The safety endpoints of this study are as follows:
incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and 
adverse events (AEs) leading to discontinuation of study drug
change from baseline in clinical laboratory test results over time 
change from baseline in vital signs over time
change from baseline in physical examination findings over time
change from baseline in body weight and height over time
change from baseline in electrocardiogram (ECG) results over time


Statistical Analysis Plan for Interventional Studies 
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change from baseline in echocardiogram (ECHO) parameters from baseline to Month 12/ET 
 
change from baseline in Tanner stage 


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Study Design
Summary of Study Design
This is a long-term, open-label, uncontrolled, multicenter study to evaluate the safety, PD, and efficacy of 
migalastat treatment in subjects over 12 years of age with Fabry disease and with amenable GLA
variants. Subjects will enroll in this study following completion of migalastat Study AT1001-020. 
Enrollment in this study should immediately follow completion of Study AT1001-020 in order to maintain 
the continuity of treatment. As appropriate, assessments performed at the End of Treatment visit for 
Study AT1001-020 will be utilized for Visit 1 (baseline) assessments for this study. 
In order to monitor safety, subsequent visits for this study were initially scheduled every 3 months with 
monthly interim telephone contacts. Following Amendment 2, the visit schedule was changed to every 6 
months, with phone contacts at intervening 3-month intervals.
Subjects will remain on the same dose of migalastat that they were receiving in Study AT1001-020. If a 
or
Subject Selection
Inclusion and exclusion criteria for this study can be found in Section 8.2 of the study protocol. Waivers of 
inclusion/exclusion criteria will not be granted.
Determination of Sample Size
As this study is an open-label extension of Study AT1001-020, no sample size calculation was performed.
Treatment Assignment and Blinding
As this study is an open-label extension of Study AT1001-020 and all subjects receive migalastat, no 
treatment assignment is conducted, and no blinding process is used for this study.
Administration of Study Medication
Migalastat will be supplied as 150-mg capsules. Migalastat capsules contain 123 mg migalastat free 
base, which is equivalent to 150 mg migalastat HCl. Migalastat will be administered every other day 
(QOD) during the treatment period. Capsules are to be taken with water at the same time of day during 
the QOD dosing schedule. Subjects will be instructed not to eat for at least 2 hours before and for 2 hours 
after administration of study drug. Water can be consumed during this period.
Study drug should not be taken on 2 consecutive days. If a dose is missed entirely for the day, the subject 
should take the missed dose of study drug only if it is within 12 hours of the time the dose normally is 
taken. If more than 12 hours have passed, the subject should resume taking study drug at the next 
planned dosing day and time according to the every-other-day dosing schedule.
Study Procedures and Flowchart
Table 1 details the schedule of assessments:


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Table 1. Schedule of Assessments 
Assessments 
Baselinea 
Treatment Period 
EOT/ ET 
Follow-
up 
Visit Interval  
  
Day 1 
Month 3 
(TC) 
Month 6 
Month 9 
(TC) 
Month 12 Month 15 
(TC) 
Month 18 
Month 21 
(TC) 
Month 24 
-- 
30-Day 
Safety 
Visit Window (days)  
  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
Informed 
consent/assent  
X  
  
  
  
  
  
  
  
  
  
  
Inclusion/exclusion 
criteria  
X  
  
  
  
  
  
  
  
  
  
  
Medical history  
X  
  
  
  
  
  
  
  
  
  
  
Concomitant 
medications  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Dosing diaryb  
X  
  
  
  
  
  
  
  
X 
 
 
FPHPQ questionnaire  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
PedsQL  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Complete physical 
examination  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Adverse events  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Vital signs (BP, HR, 
RR, Temp)  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Body weight  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Height  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Tanner Staging  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
12-lead ECG  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  


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Table 1. Schedule of Assessments (Continued) 
Assessments 
Baselinea 
Treatment Period 
EOT/ ET 
Follow-up 
Visit Interval  
  
Day 1 
Month 3 
(TC) 
Month 6 
Month 9 
(TC) 
Month 12 
Month 15 
(TC) 
Month 18 
Month 21 
(TC) 
Month 24 
-- 
30-Day 
Safety 
Visit Window (days)  
  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
±6  
+6  
Chemistry (including 
eGFR using Schwartz 
formula)  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Hematology  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Plasma lyso-Gb3, 
analogs, and 
exploratory PD 
biomarkers  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Urinalysis (urine 
protein, albumin and 
microalbumin levels)  
X  
 
X 
 
X  
 
X  
  
X 
 X 
  
Urine pregnancy test 
or date of LMP (as 
applicable)c  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Echocardiogram (LVMi 
and additional 
parameters)  
X  
  
  
  
 X 
  
  
  
X  
X  
  
Study treatment 
supply/resupply/ return  
X  
  
X  
  
 X 
 
 X 
  
X  
Xd  
  
Abbreviations: BP = blood pressure; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EOT = end of treatment; ET = early termination; FPHPQ = Fabry-Specific 
Pediatric Health and Pain Questionnaire; HR = heart rate; LMP = last menstrual period; LVMi = left ventricular mass index; lyso-Gb3 = Globotriaosylsphingosine; PD = 
pharmacodynamic; PedsQL = Pediatric Quality of Life Inventory; RR = respiration rate; TC = telephone call; Temp = body temperature  
Note: Following Month 24, visits will continue every 6 months with interim telephone contacts at 3-month intervals. The assessment schedule will repeat starting from Month 3.  
Note: For the purposes of this study, a month is considered to be 30 days.  
a End of study assessments from Study AT1001-020 will be used as baseline assessments for Study AT1001-036. 
b A dosing diary will be completed throughout the treatment period.  
c Female subjects only; urine pregnancy tests will be conducted at each site visit. For menstruating females, date of LMP will be elicited during telephone contacts.  
d Return of study drug only  


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Analysis Population
Enrolled Population 
The enrolled population will include all enrolled subjects. All safety, PD, and efficacy analyses will be 
performed using the enrolled population.
Protocol Deviations
Protocol deviations are defined as instances in which subjects or investigational site study personnel fail 
to adhere to the protocol requirements (e.g., eligibility criteria, addition or deletion of tests, dosing, 
duration of treatment, and/or any other aspect of the study design). Deviations are collected on the 
electronic Case Report Forms (eCRF). Deviations related to the COVID-19 pandemic are indicated by 
-
A list of protocol and site deviations will be provided with the date the deviation occurs, the category (eg, 
inclusion/exclusion criteria, informed consent (ICF)/subject privacy, etc.), and the description of the 
deviation. 


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General Aspects for Statistical Analysis
This section addresses the definitions, algorithms, imputations, and conventions that apply to the analysis 
and handling of the data.
General Summary Table and Individual Subject Data Listing Considerations
Summary tables and listings will have text (eg, headers or footers) providing explanatory notes that cover, 
as appropriate: date of data extraction, date of output generation, Statistical Analysis System (SAS®) 
program name, and any other output-specific details that require further elaboration. 
The descriptive summary statistics will be prepared for baseline, each visit, and change from baseline to 
each visit (if appropriate). 
Row entries in post text tables are made only if data exist for at least one subject (eg, a row with all 
zeroes will not appear). The only exception to this rule applies to tables that summarize the study 
termination status of subjects (eg, reasons for not completing the study). In this case, zeroes will appear 
for study termination reasons that no subject satisfied. The summary tables will clearly indicate the 
number of subjects to which the data apply and data that is unknown or not performed will be 
distinguished from missing data. All data collected will be reported in data listings.
Missing dates will be imputed as described in Section 5.7. Missing AE severity and relationship will be 
imputed as described in Section 5.7.2. No other missing data imputation will be performed. When imputed 
or derived data are included in the individual subject data listings, they will be flagged.
General Post Text Summary Table and Individual Subject Data Listing Format 
Considerations 
The convention will be to number tables and listings using a decimal system to reflect main levels of 
unique tables and listings and sub-levels of replicate tables and listings. The first level number will be 
consistent with the corresponding CSR appendix in which the tables or listings will appear. Thus, all post 
text tables will have a main number level 14 and listings will have a main number level 16.
Subject accounting and final disposition, analysis populations, protocol deviations and/or violations, 
demographics and baseline profile will appear as the second level number (Table 14.1 series). Efficacy 
tables will come next (Table 14.2 series). Safety tables will be at the end (Table 14.3 series). Similar 
conventions will be applied to the subject data listings and figures/graphs. 
For tables, the last line of the title will provide the analysis group being summarized (eg, Enrolled 
Population). Whether in the title or body of a table or listing, units will always be specified for all 
appropriate data. Metric system units will be used (eg, degrees Celsius [°C] for temperature, kg for body 
weight, and centimeters [cm] for height).
In general, the listings will be sorted and presented by investigational site and subject number. From left 
to right, the columns will include the subject number, visit number, visit name, visit date, treatment, and 
days relative to first dose in the study.
Data management
Datasets will be created according to Clinical Data Interchange Standards Consortium (CDISC) 
standards. The most current or latest version of the Study Data Tabulation Model (SDTM) datasets will be 
used. All statistical and data analyses, SDTMs and Analysis Data Model (ADaM) datasets will be created 


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using SAS®
created.
Data Presentation Conventions
Descriptive Statistics
Data will be summarized with descriptive statistics and/or response frequencies. For numerical data, 
descriptive statistics will include number of subjects with non-missing data (n), mean, standard deviation 
(SD), median, minimum, and maximum. For categorical data, descriptive statistics will be categorized by 
frequency counts and proportions (or percentages) of the number of subjects used in the analysis. The 
ded as appropriate, but 
the percentages will not be provided.
Rounding
In general, the minimum and maximum will be reported to the same number of decimal places as the 
data. The mean, median, and confidence intervals will be rounded to one more decimal place than the 
data. The SD will be rounded to two more decimal places than the data. Proportions will be reported as 
percentages rounded to one decimal place.
p-values
Not applicable.
Dictionaries
The Medical Dictionary for Regulatory Activities (MedDRA, version 21.0 or later version) will be used to 
code AEs and medical history into system organ class (SOC) and preferred term (PT) within SOC. The 
enhanced version of the World Health Organization Drug Dictionary (WHO-DD, WHO Drug Enhanced + 
Herbal B3 March 2018, or latest available version) will be used to code all medications (prior and 
concomitant) to anatomical therapeutic chemical (ATC) class and preferred drug names.
Baseline Definition
For all safety, PD, and efficacy data, the baseline value is defined as the last non-missing measurement 
obtained on or before the administration of the first dose of study drug in Study AT1001-036 (Day 1). 
Derived and Transformed Data
Calculations Using Dates
5.6.1.1.
Baseline Age
Age for enrolled subjects will be calculated as the truncated difference (eg, fractional part ignored) 
study- date of birth + 1 day) / 365.25]).
5.6.1.2.
Study Day
Study Day 1 denotes the day of the first dose of study drug in Study AT1001-036 and is the reference 
start date for all analyses in this study. Study days (or visit days) are defined relative to Day 1 unless 
otherwise specified. Days prior to Day 1 are negative and days after Day 1 are positive. There is no 
Day 0. That is,


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Relative Day = (Date of Assessment) 
(Date of First Dose of Study Drug) + 1, if assessment is 
on or after the date of first dose of study drug;
Relative Day = (Date of Assessment) 
(Date of First Dose of Study Drug), if assessment is 
before the date of first dose of study drug.
5.6.1.3.
Other Calculations Using Dates
Total duration of treatment will be calculated as the difference between the dates of last and first dose of 
study drug plus 1 day, regardless of any study drug interruption.
All other calculations of duration for enrolled subjects (eg, time since the primary diagnosis or age of first 
diagnosis) will be performed relative to the first dose of study drug and will follow the algorithm: 
Duration = (Target Date 
First Dose Date + 1).
5.6.1.4.
Change from Baseline
For any parameter at a specific visit, change from baseline is calculated as the value of the parameter at 
the specific visit minus the baseline value of that parameter, as defined above.
5.6.1.5.
Visit Windows
There will be no derivation for visit windows in terms of summary assessments. Nominal visits will be 
used for by-visit tables. For data with repeated observations at a given visit (eg, laboratory assessments), 
the earliest of the available non-missing values at a visit should be used in summary tables. Other 
observations will be considered as unscheduled visits.
5.6.1.6.
Multiple Assessments
If multiple assessments are associated with a nominal visit post-baseline, the first assessment will be 
used.
Handling of Missing Data
Missing Start and Stop Dates for Adverse Events
For AEs, partially missing start dates will be imputed for the purpose of determining treatment emergence 
only.
Partially missing start dates will be imputed as follows:
For a missing day,
If the month and year are equal to the month and year of the date of the first dose of study drug, 
then the date of the first dose of study drug will be used.
Otherwise, the first day of the month will be used.
For a missing day and month or just missing month,
If the year is equal to the year of the first dose of study drug, then the date of the first dose of 
study drug will be used.
Otherwise, the first day of the month and the first month of the year will be used.


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If the stop date is not missing and the imputed start date is after the stop date, then the stop date will be 
used.
If the start date is completely missing and the stop date is on or after the date of first dose of study drug, 
the AE will be considered a TEAE.
If both the start date and stop date are missing, the AE will be considered a TEAE.
Missing stop dates for AEs will not be imputed.
These imputations will be applied only to the AE summary tables. Listings will show the data as collected.
Missing Adverse Event Severity, Relationship, and Seriousness
If an AE is missing the severity or relationship to study drug, the AE will be classified under the maximum 
severity (ie, severe) or the maximum relationship (ie, definite), respectively. If the serious status is missing 
for an AE, the event will be assumed to be serious.
Missing Start and Stop Dates for Prior and Concomitant Medications
Partially missing medication start dates will be imputed in a similar manner as described in Section 5.7.1
for imputing missing AE start dates. Missing stop dates for medications will not be imputed. If when using 
these rules, the imputed start date is after the stop date, then the start date will be left as missing and the 
medication will be considered a concomitant medication for the purpose of the analysis.
Missing Exposure Dates
non-missing date of study drug dosing. 
If the month and day is missing, and the year is the same as the ICF date, the month and days 
will be imputed as the same date of ICF. Otherwise, January will be imputed for missing months 
and the 1st of the month will be imputed for missing days. 
If the days are missing and the month and year is the same as the ICF date, the days will be 
imputed as the same date of ICF. Otherwise, the first of the month will be used. 
If the end date of the last dose is missing, the last dose date will be imputed by adding 2 
multiplied by the number of doses dispensed from the last non-missing dispensation date.
Missing Baseline and Demographic Data
If partial dates are present for demographic or baseline data, the following general method will be used to 
handle them. 
For any missing days or months, the first day of the month or the first month of the year will be 
used. If the imputed dates are prior to the ICF date, they will be set as the same date of ICF.
If a year is missing and no other information is available, the date should be set to missing. (Note 
that missing year of the date of birth is not allowed in the study.)
For date of diagnosis of Fabry disease, no imputation will be done.


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Demographic, Other Baseline Characteristics and Medication
Subject Disposition and Withdrawals
Frequency counts and percentages of all subjects who are enrolled but do not take study drug, and 
subjects who are enrolled and complete the study drug/study or discontinue study drug/study early will be 
presented. All subjects who discontinue from the study will be identified, and their reason for 
discontinuation in the study will be reported. The denominators for the percentage calculations will be the 
number of subjects in the enrolled population. 
The following frequencies (number and percentage) will be displayed:
Subjects in the enrolled population
Subjects who completed the study
Subjects who discontinued early overall and by reason
A listing of all study subjects, whether they discontinued the study or not, and the reasons for study 
discontinuations will be provided for the enrolled population.
Demographic and Other Baseline Characteristics
Demographic and baseline data will be summarized by means of descriptive statistics: continuous 
variables as mean, SD, median, minimum, and maximum, and categorical variables as frequencies and 
percentages, based on the enrolled population. Demographic data will include age, sex, race, ethnicity, 
reproductive potential, height, body weight, and body mass index (BMI). Baseline characteristics will 
include number of years since diagnosis of Fabry disease, previous use of enzyme replacement therapy 
(ERT), and previous and current use of angiotensin-converting enzyme inhibitors, renin inhibitors, and 
angiotensin receptor blockers. The following calculations will be utilized: 
Age = (ICF date - date of birth + 1) / 365.25 and truncated to complete years. Age at entry into 
this study will be re-calculated based on the date of birth recorded in Study AT1001-020
Weight (in kg) = weight (in pounds) *0.4536
Height (in cm) = height (in inches) * 2.54
BMI (kg/m2) = weight(kg)/[(height(cm)/100)2], where m=meters.
Number of years since diagnosis of Fabry disease = (ICF date of this study - date of diagnosis of 
Fabry disease + 1) / 365.25 and rounded to 1 decimal.
For any missing days or months, years will be used for the calculation: Number of years since 
diagnosis of Fabry disease = (year of ICF date of this study 
year of date of diagnosis of Fabry 
disease)
For missing years, number of years will be missing.
A month will be defined as 30 days
ERT status is defined as ERT naïve at baseline and ERT experienced; ERT status is determined 
tus in Study AT1001-020.
All demographic and baseline characteristic data will also be listed.


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Medical History
A summary table of the number and percentage of subjects for medical history by SOC and PT will be 
produced for subjects in the enrolled population. Medical history will be sorted alphabetically by SOC and 
PT within the same SOC using the MedDRA coding dictionary, version 21.0, or later version. For the 
summary tables, a subject may appear more than once if he/she has more than one medical history 
coded under different SOC or PT categories. However, the subject will be counted only once in the 
overall category. A by-subject listing with coded SOC and PT along with eCRF term will also be provided. 
Concomitant Medications
Medications will be classified as prior (started prior to the first dose of study treatment in the 036 study) 
and concomitant (continued past or started on or after the first dose of study treatment in the 036 study). 
Medications starting after the last dose of study drug will not be considered as concomitant but will be 
flagged as post medications on the listing. All concomitant medications will be summarized.
All prior and concomitant medications will be classified using the ATC classification coded terms and 
preferred drug names from the WHO-DD. 
Summaries of prior and concomitant medications will be presented separately in tabular form using the 
level 4 ATC term as an upper classification level and the preferred drug name as a lower classification 
level. All medications will be summarized and sorted alphabetically by level 4 ATC term and preferred 
drug name within a given level 4 ATC term. The summary will consist of the frequency and percentage of 
subjects in the enrolled population who used the medication at least once. 
For each subject, the medication will be counted only once within a level 4 ATC term and only once under 
a given preferred drug name. A subject may appear more than once if he/she has more than one 
concomitant medication coded under different ATC terms or preferred drug names; however, the subject 
will be counted only once in the overall category. 
A by-subject listing with coded terms will also be provided along with calculated study day. 


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Efficacy
Observed values and changes from baseline for each efficacy endpoint in Section 3.2.1 will be 
summarized by subgroup, ie, sex (male, female), ERT status (ERT naïve, ERT experienced), with 
descriptive statistics at each scheduled time point based on the enrolled population. Mean plots including 
standard error bars at each visit for the numerical observed values and changes from baseline of the 
indicated laboratory assessments, ECHO results and subject questionnaires will be provided by sex 
(male, female), ERT status (ERT naïve, ERT experienced), and overall, if feasible.
Laboratory Assessments
Efficacy analyses will include summaries of observed and change from baseline values for eGFR, urine 
protein, and urine albumin for scheduled visits by subgroup, ie, sex (male, female), ERT status (ERT 
naïve, ERT experienced), indicated in Section 4.6. By-visit summary will also include the last post-
baseline values.
The eGFR will be calculated using the 2009 Schwartz formula for creatinine clearance.
A by-subject listing will be presented for each laboratory test.
Echocardiography 
A summary table of observed and change from baseline values in numerical ECHO results will be 
provided at each scheduled visit by subgroup, ie, sex (male, female), ERT status (ERT naïve, ERT 
experienced). By-visit summary will also include the last post-baseline values.
A by-subject listing will be presented for each ECHO parameter, including LVMi measurement, and other 
cardiac parameters, such as ejection fraction, fractional shortening, left ventricular internal diameter end 
diastole and end systole, midwall fractional shortening, and wall thickness.
Subject Questionnaires
Fabry-Specific Pediatric Health and Pain Questionnaire
The FPHPQ includes questions about Fabry disease-specific symptoms (eg, sweating, pain, dizziness 
and tiredness, heat and cold intolerance, swollen eyelids, gastrointestinal symptoms, feeling thirsty, 
difficulty hearing, ringing, or buzzing noise in the ears, and ability and enjoyment to participate in sports). 
The frequency of these symptoms will be rated using a 5-point Likert scale (1=Always, 2=Often, 
3=Sometimes, 4=Seldom, 5=Never). Pain severity is measured on an 11-point scale, numeric responses 
are given for onset of pain and school days missed, and yes/no questions are posed about difficulty 
hearing and other problems not specifically mentioned. 
Descriptive summaries will be provided for the FPHPQ observed and change from baseline scores by 
visit and subgroup ie, sex (male, female), ERT status (ERT naïve, ERT 6+ months ago), and overall if 
feasible. Unscheduled visits will not be included. By-visit summary will also include the last post-baseline 
values.
A by-subject listing of FPHPQ scores will be provided.
Pediatric Quality of Life Inventory
-related quality of life in healthy children and 
adolescents and those with acute and chronic health conditions. It consists of 23 items and includes 


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questions about physical functioning (8 items), emotional functioning (5 items), social functioning (5 
items), and school functioning (5 items) relative to the prior 7 days, using a 5-point scale (0=Never, 
1=Seldom, 2=Sometimes, 3=Often, 4=Always). Both parents or legally-authorized representatives and 
subjects complete the appropriate version of the PedsQLTM independently of one another. Parents or 
legally-authorized representatives and subjects may self-administer the questions after introductory 
instructions are given by study site personnel.  
PedsQLTM scoring procedure is as listed below: 
Step 1: Transform Score: 
Item scores are reversed and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 
4=0. 
Step 2: Calculate Scores: 
Score by Dimensions: 
 
If more than 50% of the items in the scale are missing, the scores should not be computed. 
 
Mean score = Sum of the items over the number of items answered. 
 
Psychosocial Health Summary Score = Sum of the items over the number of items answered in 
the Emotional, Social, and School Functioning Scales; 
 
Physical Health Summary Score = Physical Functioning Score; 
 
Total Score: Sum of all the items over the number of items answered on all the scales. 
Descriptive summary tables will be provided for the PedsQLTM observed and change from baseline of 
psychosocial, physical, and total scores by visit and subgroup, ie, sex (male, female), ERT status (ERT 
naïve, ERT experienced), and overall if feasible. By-visit summary will also include the last post-baseline 
values. 
For both the teen report and the parent of teen report, a by-subject listing of PedsQLTM scores for each 
single question as well as psychosocial, physical, and total scores will be provided. 


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Analysis of Pharmacodynamics
Primary PD Endpoint and Analysis
The PD endpoint is change in plasma levels of lyso-Gb3. Descriptive summaries will be provided for the 
observed and change from baseline values to Month 6, and Month 12 by sex (male and female), ERT 
status (ERT naïve, ERT experienced), and overall based on the enrolled population. 
A by-subject listing will also be provided.


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Safety
The analysis population used for safety analyses will be the enrolled population. Safety will be assessed 
on the basis of extent of exposure, incidence of TEAEs, SAEs and AEs leading to discontinuation, clinical 
laboratory data, vital signs including body weight and height, ECG parameters, physical examinations, 
and Tanner stage. 
Extent of Exposure and Drug Compliance
The duration of study drug exposure (in both days and months) and the number of doses of study drug 
exposure will be summarized for the enrolled population.
Duration of Exposure = end date of last dosing administration 
start date of first dosing 
administration + 1Average Dose QOD = [Total dose received/ (Duration of exposure + 1)] * 2.
Drug Compliance (%) = Average Dose QOD/Planned Dose QOD (ie, 150 mg)
Drug Compliance will be summarized using descriptive summaries. The number and percentage of 
A detailed listing of exposure to study drug and drug compliance will be presented.
Adverse Events
A TEAE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment and that begins on or after the date of the first dose of study drug in the 036 study.
Treatment-related TEAEs are defined as TEAEs that have an Investigator-defined relationship to 
-defined relationship of 
-
gs 
An overall summary of TEAEs, will be tabulated, including the number and percentage of subjects 
reporting, by sex and overall:
TEAEs
Treatment-related TEAEs
SAEs
TEAEs leading to discontinuation of study drug
TEAEs leading to death  
The number of events and incidence rates will also be provided in the overall summary table. Incidence 
rate is calculated as: total events divided by the total patient years of exposure. Total patient years of 
exposure are the sum of the duration of exposure in years for all subjects.
Further, the following TEAE summaries will be provided by sex and overall:


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Any TEAEs by SOC and PT
Any TEAEs by PT
Treatment-related TEAEs by SOC and PT
TEAEs by severity, by SOC and PT
Serious TEAEs by SOC and PT
Any non-serious TEAE by PT 
When presenting summaries by SOC and PT, subjects are counted only once within each SOC and PT. 
TEAEs will be presented alphabetically by SOC and PT.
When presenting summaries by PT, subjects are counted only once in each PT. TEAEs will be presented 
in the order of descending frequency in the overall group. 
When presenting summaries by severity, if a subject has more than one event within a given SOC or PT 
at different severities, the maximum severity will be tabulated. For example, if a subject had two events 
with the same PT, but one was moderate and the other severe, the severe TEAE will be included in the 
tabulation.
Subject listings will be provided for all AEs, TEAEs leading to discontinuation of study drug, TEAEs with 
an outcome of death, and SAEs.
Laboratory Evaluations
Clinical laboratory test values (hematology, serum chemistry, and urinalysis) and changes from baseline 
will be summarized by each visit and subgroup, ie, sex (male, female), ERT status (ERT naïve, ERT 
experienced), and overall if feasible for the enrolled population. By-visit summary will also include the last 
post-baseline values.
In addition, the following clinical summaries will be presented: 
Tables summarizing the frequencies and percentages of potential clinically significant (PCS; see 
Table 2) abnormalities at any time. The summary will indicate the number of subjects with PCS-
low or PCS-high values at any time during treatment with migalastat but will not be presented by 
visit. PCS abnormalities will be determined both by investigator assessment and derivation from 
lab alert ranges provided by Amicus. PCS abnormalities that occur at unscheduled visits will be 
included.
Tables displaying shifts from baseline to each assessment time-point, including the last post-
baseline assessment, in laboratory test values from normal to high or low using normal range 
including eGFR, urine protein, and albumin. 
Unscheduled visits will be included in PCS summaries and when determining the worst post-baseline 
assessment. 
By-subject safety laboratory listings will be generated incorporating information and assessment results 
obtained from the designated laboratory which provided normal range and reported out of range flags. All 
sented in data listings. Tests will be listed 
in alphabetical order within their respective panels (hematology, serum chemistry, and urinalysis). 
Abnormal values will be flagged.


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Table 2. Laboratory Potentially Clinically Significant Values
Chemistry
Hematology
Alkaline Phosphatase
3 x Upper Limit Normal
Hemoglobin
AST
3 x Upper Limit Normal
ALT
3 x Upper Limit Normal
Hematocrit
BUN
30 mg/dL
Creatinine
2.0 mg/dL 
RBC count (absolute)
<3.8 106/uL or > 5. 5 106/uL
CPK
White blood cells
<4.5 103/uL or >13.5 103/uL
Gamma glutamyl transferase
Neutrophils
15%
Lactate dehydrogenase 
Eosinophils
>0.7 103/uL
Glucose
Platelet count
3
3/uL
-fasting)
Urinalysis Parameter 
Chloride
< 95 mmol/L or > 110 mmol/L
Protein
Increase of 
2 units
Calcium
Albumin or microalbumin
Increase of 
2 units
Magnesium 
<1.4 mg/dL or > 2.7 mg/dL
Glucose
Increase of 
2 units
Phosphorous
<2 mg/dL or >6 mg/dL
Potassium
<3 mmol or > 6 mmol
Protein, total
<5 g/dL or > 9 g/dL
Sodium
< 130 mmol/L or > 150 mmol/L
Uric Acid 
10.5 mg/dL (male)
8.5 mg/dL (female)
Vital Signs, Body Weight and Height 
Vital signs (blood pressure, pulse rate, respiratory rate, and body temperature), height, and weight will be 
assessed at the scheduled visits specified in Section 4.6.
A summary table of observed and change from baseline values will be provided at each scheduled visit 
for the enrolled population, from baseline at Month 3, Month 6, Month 9, and Month 12 and by each 
subgroup, ie, sex (male, female), ERT status (ERT naïve, ERT experienced), and overall if feasible for the 
enrolled population. By-visit summary will also include the last post-baseline values.
The incidence rates of PCS vital sign values and changes from baseline (Table 3), by parameter, will be 
summarized. The summary will indicate the number and percentage of subjects with PCS-low and PCS-
high values at any time during treatment and will not be presented by visit.
A by-subject listing will be provided for each vital sign parameter.


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Table 3. Vital Signs Potentially Clinically Significant Values
Parameter
Baseline PCS Criterion
Post-Baseline PCS Criterion
Heart Rate
-15 (low)
Diastolic Blood Pressure
(high)
-15 (low)
Systolic Blood Pressure
-20 (low)
Weight
NA
-7% (low)
*CFB = change from baseline
Electrocardiogram Results
A summary table of observed and change from baseline values in ECG results will be provided at each 
scheduled visit for the enrolled population. A summary table displaying shifts in interpretation from 
baseline to each assessment time-point, including the last post-baseline assessment, will be provided by 
sex (male, female), ERT status (ERT naïve, ERT experienced), and overall if feasible. By-visit summary 
will also include the last post-baseline values.
A by-subject listing will be provided, including each ECG parameter: heart rate (beats per minute [bpm]), 
PR interval [msec], QRS interval [msec], QT interval mean [msec], QTc (QTcF or QTcB) [msec] and 
QTcB
Physical Examination
Complete physical examination, including HEENT (Head, Eyes, Ears, Neck and Throat), Respiratory, 
Cardiovascular, Dermatological, Lymph Nodes, Gastrointestinal, Neurological, Thyroid, Musculoskeletal 
and other assessments, will be conducted at baseline and each scheduled visit. A categorical summary 
table will be provided of the physical examination findings at each scheduled visit for the enrolled 
population by sex (male, female), ERT status (ERT naïve, ERT experienced), and overall if feasible. By-
visit summary will also include the last post-baseline values.
A by-subject listing will be presented for each body system.
Tanner Stage
A summary table of assessment results in Tanner stage will be provided at each scheduled visit by sex 
(male, female), ERT status (ERT naïve, ERT experienced), and overall if feasible for the enrolled 
population. By-visit summary will also include the last post-baseline values.
A by-subject listing will be presented for each Tanner stage parameter, including pubic hair development, 
breast development, and genital development.


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Reference List
Online source for PedsQLTM scoring:
http://www.lsebn.nhs.uk/website/X13911/files/20%20scoring_PedsQL_v13[1].pdf


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Interim Analyses
No interim analyses are planned.


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Changes from Analysis Planned in Protocol
As the subjects who receive at least 1 dose or partial dose of study drug will coincide with enrolled 
subjects in this study, the safety and intent-to-treat population have been removed and replaced with a 
ll PD and safety analyses will be conducted on the enrolled population.
No other changes are planned from the analyses described in the protocol amendment 1 (24JUN2019),


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Programming Considerations
All TLFs and statistical analyses will be generated using SAS® for Windows, Release 9.4 (SAS® Institute 
Inc., Cary, NC, USA). Computer-generated table, listing and figure output will adhere to the following 
specifications.  
General Considerations
One SAS® program can create several outputs.
Each output will be stored in a separate file.
Output files will be delivered in Word format or portable document format (pdf).
Numbering of TLFs will follow ICH E3 guidance 
Table, Listing, and Figure Format
General
All TLFs will be produced in landscape format on A4/American letter size, unless otherwise 
specified.
All TLFs will be produced using the Courier New font, size 8.
The data displays for all TLFs will have a minimum 1-inch blank margin on all 4 sides.
Headers and footers for figures will be in Courier New font, size 8.
Legends will be used for all figures with more than 1 variable, group, or item displayed.
TLFs will be in black and white (no color), unless otherwise specified.
Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text, will not be used in the TLFs, unless otherwise specified. On some occasions, 
superscripts 1, 2, or 3 may be used.
Only standard keyboard characters will be used in the TLFs. Special characters, such as non-
printable control characters, printer-specific, or font-specific characters, will not be used. 
Hexadecimal-derived characters will be used, where possible, if they are appropriate to help 
2, Cmax) will be 
employed on a case-by-case basis.
Mixed case will be used for all titles, footnotes, column headers, and programmer-supplied formats, 
as appropriate.
Headers
All output should have the following header at the top left of each page:
Amicus Therapeutics
Protocol: AT1001-020 
All output should have the Data Cut-off Date at the top right of each page.


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All output should have Page n of N at the top or bottom right corner of each page. TLFs are 
internally paginated in relation to the total length (i.e., the page number should appear sequentially 
as page n of N, where N is the total number of pages in the table).
The date output was generated should appear along with the program name as a footer on each 
page. Each table should have the relevant listing number containing the raw data as a footer.
Display Titles
Each TLF are identified by the designation and a numeral. (i.e., Table 14.1.1). ICH E3 numbering 
convention will be followed. A decimal system (x.y and x.y.z) are used to identify TLFs with related 
contents. The title is centered. The analysis population is identified on the line immediately 
following the title. The title and table designation are single spaced. A solid line spanning the 
margins will separate the display titles from the
Column headers. There will be 1 blank line between the last title and the solid line.
Table x.y.z
First Line of Title
Second Line of Title if Needed
(Enrolled Population)
Column Headers
Column headings are displayed immediately below the solid line described above in initial upper-
case characters. 
In the case of efficacy tables, the variable (or characteristic) column will be on the far left followed 
by the total column.
Analysis population sizes will be presented for each column heading as (N=xx) (or in the row 
the number of subjects in the analysis population.
Body of the Data Display
13.2.5.1.
General Conventions
Data in columns of a table or listing are formatted as follows:
Alphanumeric values are left-justified;
Whole numbers (e.g., counts) are right-justified; and
Numbers containing fractional portions are decimal aligned.
13.2.5.2.
Table Conventions
The summary tables will clearly indicate the number of subjects to which the data apply and 
unknown or not performed are distinguished from missing data.


Statistical Analysis Plan for Interventional Studies 
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SAP Version: Final 1.0 
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 Units will be included where available 
 If the categories of a parameter are ordered, then all categories between the maximum and 
minimum category are presented in the table, even if n=0 in a given category that is between the 
minimum and maximum level for that parameter. For example, the frequency distribution for 
symptom severity would appear as: 
Severity 
Rating 
N 
severe 
0 
moderate 
8 
mild 
3 
 
Where percentages are presented in these tables, zero percentages will not be presented and so counts 
of 0 will be presented as 0 and not as 0 (0%). 
 If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation from the 
Study, etc.), then only those categories for which there is at least 1 subject represented in 1 or 
more groups are included. 
 An Unknown or Missing category are added to each parameter for which information is not 
available for 1 or more subjects.  
 Unless otherwise specified, the estimated mean and median for a set of values are printed out to 1 
more significant digit than the original values, and SD are printed out to 2 more significant digits 
than the original values. The minimum and maximum should report the same significant digits as 
the original values. For example, for systolic blood pressure: 
n 
  XX 
Mean 
XXX.X 
SD 
     X.XX 
Median 
XXX.X 
Minimum 
XXX 
Maximum 
XXX 
 
 P-values are output in the 
-
values less than 0.001 will be presented as <0.001. If a p-value is less than 0.0001, then present 
as <0.0001. If the p-value is returned as >0.999, then present as >0.999. 
 Percentage values are printed to one decimal place, in parentheses with no spaces, one space 
after the count (e.g., 7 (12.8%), 13 (5.4%)). Unless otherwise noted, for all percentages, the 
number of subjects in the analysis population who have an observation will be the denominator. 
Percentages equating to 100% are presented as 100%, without decimal places.  
 Tabular display of data for medical history, prior/concomitant medications, and all tabular displays 
of AE data are presented by the body system, treatment class, or SOC, PT, assuming all terms are 
coded. If incidence for more than 1 term is identical, they should then be sorted alphabetically. 
Missing descriptive statistics or p-
-  


Statistical Analysis Plan for Interventional Studies
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This document is confidential.
SAP Version: Final 1.0
Controlled Document ID: 3903A.00, Effective Date 30Apr2018
Page 35 of 37
The percentage of subjects is normally calculated as a proportion of the number of subjects 
assessed for the analysis population presented. However, careful consideration is required in many 
instances due to the complicated nature of selecting the denominator, usually the appropriate 
number of subjects. Describe details of this in footnotes or programming notes.
For categorical summaries (number and percentage of subjects) where a subject can be included 
in more than one category, describe in a footnote or programming note if the subject is included in 
the summary statistics for all relevant categories or just 1 category and the criteria for selecting the 
criteria.
Where a category with a subheading (such as system organ class) has to be split over more than 
one page, output the subheading f
overall summary statistics for the subheading should only be output on the first relevant page.
13.2.5.3.
Listing Conventions
Listings will include days relative to the initiation of treatment as applicable.
Listings will be sorted for presentation in order of subject number, visit/collection day, and 
visit/collection time.
-
-
whichever is appropriate.
Dates are printed in SAS®
are represented on subject listings as dashes (--JUL2000). Dates that are missing because they 
All observed time values are to be presented using a 24-hour clock HH:MM or HH:MM:SS format 
(e.g., 11:26:45, or 11:26). Time will only be reported if it was measured as part of the study.
Units will be included where available
13.2.5.4.
Figure Conventions
Unless otherwise specified, for all figures, study visits will be displayed on the X-axis and endpoint 
(e.g., treatment mean change from Baseline) values will be displayed on the Y-axis.
Footnotes
A solid line spanning the margins will separate the body of the data display from the footnotes. 
All footnotes will be left justified with single-line spacing immediately below the solid line 
underneath the data display.
reference footnote. Each new footnote should start on a new line, where possible.
Subject specific footnotes are avoided, where possible.


Statistical Analysis Plan for Interventional Studies 
Sponsor: Amicus Therapeutics; Protocol No.: AT1001-036 
 
This document is confidential. 
SAP Version: Final 1.0 
Controlled Document ID: 3903A.00, Effective Date 30Apr2018 
Page 36 of 37 
 Footnotes will be used sparingly and add value to the table, figure, or data listing. If more than six 
lines of footnotes are planned, then a cover page may be used to display footnotes, and only those 
essential to comprehension of the data will be repeated on each page.  
 The last line of the footnote section will be a standard source line that indicates the name of the 
program used to produce the data display, date the program was run, and the listing source (ie, 
Program: 
 


Statistical Analysis Plan for Interventional Studies
Sponsor: Amicus Therapeutics; Protocol No.: AT1001-036
This document is confidential.
SAP Version: Final 1.0
Controlled Document ID: 3903A.00, Effective Date 30Apr2018
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Quality Control
SAS® programs are developed to produce output such as analysis data sets, summary tables, data 
listings, figures, or statistical analyses. An overview of the development of programs is detailed in Syneos 
Health Standard Operating Procedure (SOP) Developing Statistical Programs (3907).
Syneos Health SOPs Developing Statistical Programs (3907) and Quality Deliveries (SDTM, ADaM, TLF)
(3908) describes the quality control procedures that are performed for all SAS® programs and output. 
Quality control is defined here as the operational techniques and activities undertaken to verify that the 
SAS® programs produce the output by checking for their logic, efficiency and commenting and by review 
of the produced output.