A Phase 3 Open-label Extension Study to Assess the Long-term Safety and Efficacy of Intravenous ATB200 Co-administered With Oral AT2221 in Adult Subjects With Late-onset Pompe Disease (LOPD)
Phase: PHASE3
Conditions: Pompe Disease (Late-onset)
Sponsor: Amicus Therapeutics

Official Title: 
A Phase 3 Open-Label Extension Study to Assess the 
Long-Term Safety and Efficacy of Intravenous 
Infusions of ATB200 Co-Administered with Oral 
AT2221 in Adult Subjects With Late-Onset Pompe 
Disease 
 
 
NCT Number: 
NCT04138277 
 
 
Document Date:  
Amendment 3: 10 December 2024 
 

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
A PHASE 3 OPEN-LABEL EXTENSION STUDY TO ASSESS 
THE LONG-TERM SAFETY AND EFFICACY OF 
INTRAVENOUS ATB200 CO-ADMINISTERED WITH ORAL 
AT2221 IN ADULT SUBJECTS WITH LATE-ONSET POMPE 
DISEASE 
 
Protocol Number: ATB200-07 
Amendment 3: 10 December 2024 
(Supersedes Amendment 2: 26 April 2023) 
EudraCT Number: 2019-000954-67 
EU CTR # 2023-505170-15-00 
US IND Number: 127,387 
Compounds: ATB200 (cipaglucosidase alfa) and AT2221 (miglustat) 
 
Sponsor 
Amicus Therapeutics, Inc. 
47 Hulfish Street 
Princeton, NJ 08542, USA 
 
 
 
 
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. 

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DOCUMENT HISTORY 
Protocol ATB200-07 Document History 
Document Number 
Document Date 
Amendment 2 
26 April 2023 
Amendment 1 
2 October 2020 
Original Protocol 
25 March 2019 

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SUMMARY OF CHANGES TO THE PROTOCOL 
The previous version of this document (Amendment 2: 26 April 2023) was modified to create the 
current version (Amendment 3: 10 December 2024). 
Table 1: 
Summary of Changes to the Protocol 
Document History 
Version and Date of Document 
Comments 
Original Version: 25 March 2019 
 
Amendment 1: 2 October 2020 
• 
Administrative updates 
• 
Update to number of study sites 
• 
Update to study objectives 
• 
Removal of text related to new subjects in Japan 
• 
Addition of COVID-19-related changes 
• 
Clarification to inclusion criteria 
• 
Clarification to duration of treatment 
• 
Addition of efficacy endpoint (6-minute walk distance 
predicted value) 
• 
PK endpoints revised 
• 
Summary of known and potential risks and benefits 
updated following HA request 
• 
Withdrawal criteria updated 
• 
Subjects of reproductive potential updated 
• 
New physical description of miglustat added 
• 
Temperatures for study drug storage revised 
• 
Clarification for weight collection for calculation of 
miglustat dose 
• 
Schedule of assessments updated 
• 
Separate PK sampling schedule included for Japanese 
subjects 
• 
Infusion visits and home infusion visits updated 
• 
Retrospective data collection removed 
• 
Clarification for how adverse events during 
Study ATB200-03 that are still ongoing in this study will 
be recorded 
• 
Clarification to overdose/underdose included 
• 
Informed consent text revised 

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Table 1: 
Summary of Changes to the Protocol (Continued) 
Document History 
Version and Date of Document 
Comments 
Amendment 2: 26 April 2023 
• 
Administrative updates 
• 
Study end date extended 
• 
Analysis population definitions updated 
• 
Statistical methods section updated to refer to the 
statistical analysis plan 
• 
Addition of text to comply with EU clinical trial 
regulation requirements 
• 
Duration of study updated 
• 
Addition of definition of study completer 
• 
Clarification to withdrawal criteria 
• 
Update to study drug storage for temperature incursions 
• 
Cipaglucosidase alfa section updated to clarify an 
inconsistency regarding the weight entry 
• 
Miglustat section updated to clarify inconsistency 
regarding weight entry and additional dosing instructions 
• 
Prohibited medications list updated 
• 
Schedule of assessments updated 
• 
Infusion visits and home infusion visits section updated 
• 
End of study and early termination section updated 
• 
Follow-up period section updated 
• 
Text added for data privacy regulations 
• 
Clarification added to immunogenicity assessments 
section 
• 
Adverse event assessment of severity updated to align 
with the electronic case report form 
• 
Clarification of overdose/underdose definitions 
• 
Clarification to missed dose section 
• 
Addition of text for EU general data protection regulation 
requirements 

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Table 1: 
Summary of Changes to the Protocol (Continued) 
Document History 
Version and Date of Document 
Comments 
Amendment 3: 10 December 2024 
The purpose of this amendment is to continue collecting 
long-term safety and efficacy data on LOPD subjects treated 
with cipaglucosidase alfa/miglustat while decreasing some of 
the burden on those subjects taking part, and continuing to 
provide treatment where regulatory approval has not yet been 
granted or the product is not yet commercially available. 
Subjects may continue in this study until commercial 
cipaglucosidase alfa/miglustat becomes available in their 
country as a treatment for Pompe patients. 
• 
Administrative updates 
• 
Removal of COVID-19-related procedures 
• 
Duration of treatment updated 
• 
Definition of the end of study updated to include that the 
CSR will be written based on a data cutoff date of 
31 December 2024. Any data collected after the data 
cutoff date will be provided as an addendum to the final 
CSR. 
• 
Clarification to infusion visits and home infusion visits 
section 
• 
Appendix added for subjects who continue in the study 
after Amendment 3 is approved. Information includes: 
− 
Objectives to align with reducing the burden of 
participation for subjects 
− 
Reduced efficacy assessments updated to align with 
reducing the burden of participation for subjects 
− 
A new schedule of assessments for subjects who 
continue in the study 
− 
Data analysis and statistical considerations for 
subjects continuing in the study 
Abbreviations: COVID-19 = Coronavirus disease 2019; CSR = clinical study report; HA = health authority; 
LOPD = late-onset Pompe disease; PK = pharmacokinetic 
Table 2: 
Serious Adverse Event Contact Information 
Role 
Contact Information 
Reporting of serious adverse events 
Safety FAX number: +1 866-422-1278 
Email address: safetyreporting@amicusrx.com 

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2. 
DECLARATIONS OF SPONSOR AND INVESTIGATOR 
2.1. 
Declaration of Sponsor 
This clinical study protocol is subject to critical review and has been approved by Amicus 
Therapeutics (Amicus). 
The information it contains is consistent with the following: 
• the current benefit-risk evaluation of ATB200 (cipaglucosidase alfa, recombinant 
human acid α-glucosidase) co-administered with AT2221 (miglustat, 
N-butyl-deoxynojirimycin) 
• the moral, ethical, and scientific principles governing clinical research, as set out in 
the current version of Declaration of Helsinki and the principles of Good Clinical 
Practice (GCP) described in the United States (US) Code of Federal Regulations 
(CFR) 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 cipaglucosidase alfa co-administered with miglustat. 
 
 
Date: 
 
Signature: 
 
Amicus Therapeutics 
2.2. 
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 
Declaration of Helsinki and the principles of GCP described in the US CFR Parts 50, 54, 56, and 
312 and in the ICH GCP E6 guidelines. I will also work in accordance with applicable local 
requirements. 
Date: 
 
Signature: 
 
Printed Name: 
 
 
Docusign Envelope ID: 400AF9C1-1AB4-4B57-BF2F-82D3F7C17C0A
17 December 2024 | 09:03 EST

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3. 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: Amicus Therapeutics (Amicus) 
Name of Investigational Products: ATB200 (cipaglucosidase alfa) and AT2221 (miglustat) 
Name of Active Ingredients: 
Cipaglucosidase alfa: Recombinant human acid α-glucosidase (rhGAA) 
Miglustat: N-butyl-deoxynojirimycin 
Cipaglucosidase alfa/miglustat: cipaglucosidase alfa co-administered with miglustat 
Title of Study: A Phase 3 Open-label Extension Study to Assess the Long-term Safety and Efficacy of 
Intravenous ATB200 Co-administered with Oral AT2221 in Adult Subjects with Late-onset Pompe 
Disease 
Study Sites: Up to approximately 59 sites globally 
Phase of Development: 3 
Objectives: 
This amendment aims to continue collecting long-term safety and efficacy data on LOPD subjects 
treated with cipaglucosidase alfa/miglustat while reducing subject burden and providing treatment 
where regulatory approval or commercial availability is pending. The objectives for the study are 
presented here and the objectives for the amendment are provided in Appendix 1. 
Primary 
The primary objective of this study is to assess the long-term safety and tolerability of ATB200 
(cipaglucosidase alfa)/AT2221 (miglustat) co-administration. 
Secondary 
The secondary objectives of this study are as follows: 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
ambulatory function, as measured by the 6-minute walk test (6MWT) 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
pulmonary function, as measured by sitting forced vital capacity (FVC) (% predicted) 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
muscle strength 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
health-related patient-reported outcomes 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
motor function 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
overall clinical impression, as assessed by both physician and subject 
• 
to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration on 
measures of pulmonary function other than FVC (% predicted) 
• 
to assess the long-term effect of cipaglucosidase alfa/miglustat co-administration on 
biomarkers of muscle injury and disease substrate 
• 
to assess the immunogenicity of cipaglucosidase alfa/miglustat co-administration 

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• 
to characterize the pharmacokinetics (PK) of cipaglucosidase alfa and miglustat and using 
plasma total GAA protein level by signature peptide and plasma miglustat concentration 
assays in subjects at sites in Japan only 
Methodology: 
This is a multicenter, international open-label extension study of cipaglucosidase alfa/miglustat in adult 
subjects with late-onset Pompe disease (LOPD) who completed Study ATB200-03. 
The final analysis of the complete data set will be performed for the final CSR based on a data cutoff 
date of 31 December 2024. Upon approval of this amendment, any subjects continuing in the study 
will follow an updated Schedule of Assessments (Appendix 1). An addendum to the final CSR will be 
produced once the remaining subjects have completed the study. 
For subjects who participated in Study ATB200-03, the first infusion visit in this study should be 
scheduled approximately 2 weeks after the last visit in Study ATB200-03 in an effort to ensure 
continued administration of study drug on the same schedule with no gap between studies. Infusion 
visits for administration of study drug will be scheduled every 2 weeks throughout the study; 
assessments (eg, clinical laboratory tests) for monitoring of initial safety will be performed at these 
infusion visits for the first 6 weeks of the study. Subjects may be eligible for administration of study 
drug at their home after 3 months in the study if they have not had a moderate to severe 
infusion-associated reaction (IAR) during those 3 months. During the conduct of the study, the 
SARS-CoV-2 (COVID-19) pandemic emerged and impeded the conduct of site visits and laboratory 
testing due to quarantines, travel restrictions, and risk of infection. With the intention of maintaining 
regular infusions, home infusions will be allowed prior to completing Week 12 wherever possible for 
subjects who may be eligible. If infusions were missed near the scheduled assessments on Week 12, 
Week 26, or at any of the study visits scheduled every 26 weeks after Week 26, it should be 
communicated with Amicus on a case-by-case basis to determine whether catch-up infusions are 
needed and how many catch-up infusions are needed prior to the study assessments. Study visits that 
include efficacy, safety, and other assessments will be scheduled approximately every 3 months for the 
first 6 months, then every 6 months thereafter. These visits may occur over 2 days, provided all study 
assessments and procedures (with the exception of PK sample collection) are performed before 
administration of study drug. 
Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function (6MWT), 
motor function tests (Gait, Stairs, Gowers’ maneuver, and Chair [GSGC] test and Timed Up and Go 
[TUG] test), muscle strength (manual muscle testing and quantitative muscle testing), and pulmonary 
function tests (forced vital capacity [FVC], slow vital capacity [SVC], maximal inspiratory pressure 
[MIP], maximal expiratory pressure [MEP], and sniff nasal inspiratory pressure [SNIP]). 
Patient-reported outcomes include the Rasch-built Pompe-specific Activity (R-PAct) Scale, EuroQol 
5 Dimensions-5 Levels Instrument (EQ-5D-5L), Patient-reported Outcomes Measurement Information 
System (PROMIS®) instruments for physical function, fatigue, dyspnea, and upper extremity, and 
Subject’s Global Impression of Change (SGIC). The Physician’s Global Impression of Change (PGIC) 
will also be performed. Pharmacodynamic (PD) assessments include measurement of biomarkers of 
muscle injury (creatine kinase [CK]) and disease substrate (urinary hexose tetrasaccharide [Hex4]). 
Blood samples for PK assessment of total GAA protein and miglustat concentration in plasma will be 
collected from subjects at sites in Japan only. Safety assessments include monitoring of adverse events 
(AEs), including IARs, clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, 
physical examinations including weight, electrocardiograms (ECGs), and immunogenicity. 
Concomitant medications and nondrug therapies will also be recorded. 
Number of Subjects (Planned): 
The maximum sample size for this study is based on the number of subjects who complete 
Study ATB200-03, estimated to be approximately 110 subjects. 

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Diagnosis and Main Criteria for Inclusion: 
Subjects Who Participated in Study ATB200-03 
Inclusion Criteria 
1. Subject must provide signed informed consent prior to any study-related procedures being 
performed. If the subject is under 20 years of age, the subject must provide written informed 
consent. In Japan, the subject’s parental guardian (or legal representative) must also sign the 
informed consent form. 
2. Subject must have completed Study ATB200-03. 
Note: Subjects who were forced to withdraw from Study ATB200-03 for a logistical reason not 
related to the efficacy or safety of cipaglucosidase alfa/miglustat (eg, hospitalization for a car 
accident, COVID-19 pandemic, or emergency surgery) and which resulted in several 
consecutive missed doses may be eligible to participate in this study upon approval by the 
Amicus medical monitor. 
3. Female subjects of childbearing potential and male subjects must agree to use medically 
accepted methods of contraception during the study and for 90 days after the last dose of study 
drug. 
Exclusion Criteria 
1. Subject plans to receive gene therapy or participate in another interventional study for Pompe 
disease. 
2. Subject has a hypersensitivity to any of the excipients in cipaglucosidase alfa or miglustat, or 
has a medical condition or any other extenuating circumstance that may, in the opinion of the 
investigator or medical monitor, pose an undue safety risk to the subject or may compromise 
his/her ability to comply with or adversely impact protocol requirements. This includes clinical 
depression (as diagnosed by a psychiatrist or other mental health professional) with 
uncontrolled or poorly controlled symptoms. 
3. Subject, if female, is pregnant or breastfeeding. 
4. Subject, whether male or female, is planning to conceive a child during the study. 
Investigational Product, Dosage, and Mode of Administration: 
Cipaglucosidase alfa/miglustat will be co-administered as follows: miglustat 260 mg (4 × 65-mg oral 
capsules) for subjects weighing ≥ 50 kg and 195 mg (3 × 65-mg oral capsules) for subjects weighing 
≥ 40 kg to < 50 kg, followed approximately 1 hour later by cipaglucosidase 20 mg/kg (reconstituted 
lyophilized drug product, 105 mg/vial), administered over a 4-hour intravenous [IV] infusion. The 
cipaglucosidase alfa/miglustat combination regimen will be administered every 2 weeks. 
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of miglustat. 
Duration of Treatment: 
Treatment with open-label cipaglucosidase alfa/miglustat will be administered within this study 
protocol until one of the following conditions apply: 
• 
the product is approved and commercialized for use in the investigational study 
population, or 
• 
cipaglucosidase alfa/miglustat is rejected by the regulatory authority in the subject’s local 
country as an approved treatment for Pompe disease, or 
• 
the sponsor decides to continue to provide cipaglucosidase alfa/miglustat via a post-trial 
access mechanism, or 

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• 
the subject is withdrawn or withdraws consent, or 
• 
the sponsor decides to end the study. 
Reference Therapy, Dosage, and Mode of Administration: 
None. 
Criteria for Evaluation: 
The long-term safety profile of cipaglucosidase alfa/miglustat will be characterized using incidence of 
treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to 
discontinuation of study drug, frequency and severity of immediate and late IARs, and any 
abnormalities noted in other safety assessments (eg, clinical laboratory tests, ECGs, vital signs). 
Immunogenicity to cipaglucosidase alfa will also be described. 
Efficacy endpoints are as follows: 
• 
change from baseline 6-minute walk distance (6MWD) 
• 
change from baseline in 6MWD (% predicted) 
• 
change from baseline in sitting FVC (% predicted) 
• 
change from baseline in the manual muscle test score for the lower extremities 
• 
change from baseline in the total score for the PROMIS – physical function 
• 
change from baseline in the total score for the PROMIS – fatigue 
• 
change from baseline in the following variables related to motor function: 
− 
GSGC total score 
− 
time to complete the 10-meter walk (ie, assessment of gait) of the GSGC test 
− 
time to complete the 4-stair climb of the GSGC test 
− 
time to complete the Gowers’ maneuver of the GSGC test 
− 
time to arise from a chair as part of the GSGC test 
− 
change from baseline in the time to complete the TUG test 
• 
change from baseline in the following variables related to muscle strength: 
− 
manual muscle test score for the upper extremities 
− 
manual muscle test total score (upper and lower extremities combined) 
− 
quantitative muscle test value (kg) for the upper extremities 
− 
quantitative muscle test value (kg) for the lower extremities 
− 
quantitative muscle test total value (kg) (upper and lower extremities combined) 
• 
change from baseline in the following variables from patient-reported outcome measures: 
− 
total score for the PROMIS – dyspnea 
− 
total score for the PROMIS – upper extremity 
− 
R-PAct Scale total score 
− 
EQ-5D-5L health status 
• 
actual value of the subject’s functional status (improving, stable, or declining) pertaining 
to the effects of study drug in the following areas of life, as measured by the SGIC: 
− 
overall physical well-being 
− 
effort of breathing 

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− 
muscle strength 
− 
muscle function 
− 
ability to move around 
− 
activities of daily living 
− 
energy level 
− 
level of muscular pain 
• 
actual value of the subject’s functional status (improving, stable, or declining), as 
measured by the PGIC 
• 
change from baseline in the following measures of pulmonary function, as follows: 
− 
sitting SVC (% predicted) 
− 
MIP (cmH2O) 
− 
MIP (% predicted) 
− 
MEP (cmH2O) 
− 
MEP (% predicted) 
− 
SNIP (cmH2O) 
Pharmacodynamic endpoints are as follows: 
• 
change from baseline in serum CK level 
• 
change from baseline in urinary Hex4 level 
Pharmacokinetic endpoints (applicable for subjects at sites in Japan only): 
• 
sparse blood sampling for determination of total GAA protein levels and miglustat 
concentrations in plasma for a population PK analysis 
Pharmacokinetic endpoints derived from a population PK analysis of total GAA protein and miglustat 
concentrations will be provided in a separate modeling and simulation plan. 
Statistical Methods: 
Analysis Populations 
The open-label extension enrolled subjects (OLE-ES) is a subset of the ATB200-03 intent-to-treat 
(ITT) population, and it includes all subjects who satisfied the eligibility requirements (based on the 
inclusion and exclusion criteria) and entered Study ATB200-07. This population will be used for the 
analyses of all efficacy and pharmacodynamic endpoints involving Studies ATB200-03 and 
ATB200-07 integrated data. 
The open-label extension full analysis set (OLE-FAS) includes all subjects who entered the OLE 
Study ATB200-07 who had both a valid baseline and at least one post-baseline assessment for at least 
1 of these efficacy endpoints (6MWD, sitting % predicted FVC, MMT-lower extremities, 
PROMIS – physical function, PROMIS – fatigue, and GSGC). This analysis set will be used for the 
analyses of the main efficacy and pharmacodynamic endpoints involving Study ATB200-07 
stand-alone data. 
The open-label extension safety population includes all subjects who took at least 1 dose of 
cipaglucosidase alfa/miglustat co-administration in Study ATB200-07. This population will be used for 
the summaries of medical history, drug exposure, and any other specific safety-related summaries for 
Study ATB200-07 stand-alone data. 
The safety population consists of all subjects who took at least 1 dose of study drug in either 
Study ATB200-03 or Study ATB200-07. This population will be analyzed per the actual treatment 
received and will be used for all integrated safety summaries. 

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The treatment switched population is defined as subjects who were randomized to and received 
alglucosidase alfa/placebo in Study ATB200-03 and subsequently received cipaglucosidase 
alfa/miglustat in Study ATB200-07. This population will be used for specific analyses involving these 
treatment-switched subjects. 
Treatment Groups 
Appropriate reporting treatment groups will be defined in the statistical analysis plan for all analyses 
involving ATB200-07 stand-alone data as well as ATB200-03 and ATB200-07 integrated data. 
Efficacy Analyses 
In general, continuous data will be summarized using descriptive statistics, and categorical data will be 
summarized using counts and percentages. Specific analysis details and display format will be 
described in the statistical analysis plan. 
Ambulatory Function, Motor Function, Pulmonary Function, and Muscle Strength Endpoints 
The OLE-FAS and OLE-ES populations will be used for the analysis of 6MWD, FVC % predicted, 
GSGC total score, other manual muscle tests, quantitative muscle tests, and other pulmonary function 
tests. The % predicted 6MWD will also be summarized, where the predicted value will be calculated 
using the reference equations from Enright and Sherill (Enright and Sherill 1998). These continuous 
endpoints will be summarized by treatment group and visit. The change from baseline will be similarly 
summarized by treatment group and visit, and the 95% confidence intervals for the mean change will 
be provided for each treatment group. In addition, these analyses will be conducted on the treatment 
switched population (where applicable) for 6MWD and FVC % predicted. 
Patient-reported Outcomes and Physician’s Global Impression of Change 
The OLE-FAS and OLE-ES populations will be used for patient-reported outcome analyses. Summary 
of each item as well as total score (raw total score and change from baseline in total score) for the 
R-PAct Scale, EQ-5D-5L (domain scores are to be analyzed as both categorical and continuous 
variables), and PROMIS instruments will be summarized by treatment group and visit. The change 
from baseline in the total scores will be summarized by treatment group and visit, and the 
95% confidence intervals for the mean change will be provided for each treatment group. 
Each item/domain of the SGIC will be summarized by treatment group and visit. The scores will be 
analyzed as both categorical and continuous variables. Additionally, the response scale for each item 
will be divided into 3 categories (improving, stable, or declining) which reflect the functional status, 
and these will be summarized by treatment group. 
Summary of response score for actual values for PGIC will be summarized by treatment group and 
visit. 
Biomarker Analyses 
The OLE-ES population will be used for biomarker analyses involving serum CK and urinary Hex4. 
These continuous endpoints will be summarized by treatment group and visit. Changes from baseline 
will be similarly summarized by treatment group and visit, and the 95% confidence intervals for the 
mean and/or median change will be provided for each treatment group. 
Pharmacokinetic Analyses 
Pharmacokinetic endpoints from a population PK analysis of total GAA protein and miglustat 
concentrations will be provided in a separate modeling and simulation plan. 

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Safety Analyses 
Safety analyses will be based on the safety population (for ATB200-03 and ATB200-07 integrated 
data) as well as the open-label extension safety population (for ATB200-07 stand-alone data). 
Safety data will be summarized using descriptive statistics for continuous data and using counts and 
percentages for categorical data. 
The effect of immunogenicity results on efficacy and safety will be explored. Analysis of 
immunogenicity data will be described separately. 

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4. 
TABLE OF CONTENTS 
1. 
TITLE PAGE ........................................................................................................... 1 
DOCUMENT HISTORY ............................................................................................................ 2 
SUMMARY OF CHANGES TO THE PROTOCOL ................................................................... 3 
2. 
DECLARATIONS OF SPONSOR AND INVESTIGATOR ..................................... 6 
2.1. 
Declaration of Sponsor ............................................................................................. 6 
2.2. 
Declaration of Investigator........................................................................................ 6 
3. 
PROTOCOL SYNOPSIS.......................................................................................... 7 
4. 
TABLE OF CONTENTS ........................................................................................ 14 
5. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................. 19 
6. 
INTRODUCTION .................................................................................................. 21 
6.1. 
Pompe Disease ....................................................................................................... 21 
6.2. 
Cipaglucosidase Alfa/Miglustat .............................................................................. 22 
6.2.1. 
Cipaglucosidase Alfa .............................................................................................. 22 
6.2.2. 
Miglustat ................................................................................................................ 22 
6.3. 
Human Dosing Rationale ........................................................................................ 23 
6.3.1. 
Cipaglucosidase Alfa .............................................................................................. 23 
6.3.2. 
Miglustat ................................................................................................................ 24 
6.4. 
Nonclinical Studies ................................................................................................. 24 
6.5. 
Clinical Studies....................................................................................................... 25 
6.6. 
Summary of Known and Potential Risks and Benefits ............................................. 25 
6.7. 
Study Population .................................................................................................... 26 
7. 
STUDY OBJECTIVES........................................................................................... 27 
7.1. 
Primary Objective ................................................................................................... 27 
7.2. 
Secondary Objectives ............................................................................................. 27 
8. 
INVESTIGATIONAL PLAN ................................................................................. 28 
8.1. 
Study Design .......................................................................................................... 28 
8.2. 
Duration of Study ................................................................................................... 29 
8.3. 
Criteria for Termination of the Study ...................................................................... 29 
8.4. 
Definition of the End of Study ................................................................................ 29 
8.5. 
Definition of Study Completer ................................................................................ 29 
8.6. 
Discussion of Study Design, Including Choice of Control Groups........................... 30 

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9. 
SUBJECT SELECTION AND WITHDRAWAL CRITERIA ................................. 31 
9.1. 
Number of Subjects ................................................................................................ 31 
9.2. 
Eligibility Criteria ................................................................................................... 31 
9.2.1. 
Subjects Who Participated in Study ATB200-03 ..................................................... 31 
9.2.1.1. 
Inclusion Criteria .................................................................................................... 31 
9.2.1.2. 
Exclusion Criteria ................................................................................................... 31 
9.3. 
Withdrawal Criteria ................................................................................................ 32 
9.4. 
Subjects of Reproductive Potential ......................................................................... 32 
10. 
TREATMENT OF SUBJECTS .............................................................................. 34 
11. 
STUDY DRUG MATERIALS AND MANAGEMENT ......................................... 35 
11.1. 
Study Drug ............................................................................................................. 35 
11.2. 
Study Drug Packaging and Labeling ....................................................................... 35 
11.3. 
Study Drug Storage ................................................................................................ 36 
11.4. 
Study Drug Preparation .......................................................................................... 36 
11.5. 
Administration ........................................................................................................ 36 
11.5.1. 
Cipaglucosidase Alfa .............................................................................................. 36 
11.5.2. 
Miglustat ................................................................................................................ 37 
11.6. 
Randomization and Blinding................................................................................... 37 
11.7. 
Study Drug Accountability ..................................................................................... 37 
11.8. 
Study Drug Handling and Disposal ......................................................................... 38 
11.9. 
Prohibited Medications ........................................................................................... 38 
12. 
STUDY PARAMETERS AND PROCEDURES..................................................... 39 
12.1. 
Schedule of Assessments ........................................................................................ 39 
12.2. 
Additional Details on Study Visits .......................................................................... 45 
12.2.1. 
Day 1 for Subjects who Participated in Study ATB200-03 ...................................... 45 
12.2.2. 
Infusion Visits and Home Infusion Visits ................................................................ 45 
12.2.3. 
Post-baseline Assessment Visits ............................................................................. 47 
12.2.4. 
Unscheduled Visits ................................................................................................. 47 
12.2.5. 
End of Study/Early Termination ............................................................................. 47 
12.2.6. 
Follow-up Period .................................................................................................... 47 
12.3. 
Description of Study Assessments .......................................................................... 47 
12.3.1. 
Demographic Data Collection ................................................................................. 48 
12.3.2. 
Medical History ...................................................................................................... 48 

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12.3.3. 
Prior/Current Medications....................................................................................... 48 
12.3.4. 
Physical Examination ............................................................................................. 48 
12.3.5. 
Body Weight and Height ........................................................................................ 48 
12.3.6. 
Vital Signs .............................................................................................................. 49 
12.3.7. 
Adverse Events ....................................................................................................... 49 
12.3.8. 
Patient-reported Outcomes ...................................................................................... 49 
12.3.9. 
Physician’s Global Impression of Change ............................................................... 50 
12.3.10. 
Electrocardiogram .................................................................................................. 50 
12.3.11. 
Clinical Laboratory Tests ........................................................................................ 50 
12.3.11.1. Chemistry, Hematology, and Urinalysis .................................................................. 50 
12.3.11.2. Pregnancy Tests ...................................................................................................... 51 
12.3.12. 
Immunogenicity Assessments ................................................................................. 51 
12.3.13. 
Sample Collection for Pharmacokinetic Assessments (Sites in Japan Only) ............ 52 
12.3.14. 
Creatine Kinase and Urinary Hexose Tetrasaccharide ............................................. 52 
12.3.15. 
Biological Specimens ............................................................................................. 52 
12.3.16. 
Pulmonary Function Tests ...................................................................................... 53 
12.3.17. 
Motor Function Tests .............................................................................................. 53 
12.3.18. 
6-Minute Walk Test ................................................................................................ 53 
12.3.19. 
Muscle Strength Testing ......................................................................................... 54 
13. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ................................. 55 
13.1. 
Definitions .............................................................................................................. 55 
13.1.1. 
Adverse Events ....................................................................................................... 55 
13.1.2. 
Serious Adverse Events .......................................................................................... 55 
13.1.3. 
Infusion-associated Reactions ................................................................................. 57 
13.1.4. 
Relationship to Study Drug ..................................................................................... 59 
13.1.5. 
Assessment of Severity ........................................................................................... 60 
13.2. 
Reporting of Adverse Events .................................................................................. 60 
13.3. 
Reporting Requirements for Serious Adverse Events .............................................. 61 
13.3.1. 
Additional Reporting Requirements for Suspected Unexpected Serious 
Adverse Reaction.................................................................................................... 62 
13.3.2. 
Overdose/Underdose............................................................................................... 62 
13.3.3. 
Missed Dose ........................................................................................................... 63 
13.4. 
Reporting of Pregnancy .......................................................................................... 63 

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14. 
DATA MANAGEMENT ........................................................................................ 65 
15. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ........................... 66 
15.1. 
Endpoints ............................................................................................................... 66 
15.1.1. 
Safety Endpoints ..................................................................................................... 66 
15.1.2. 
Efficacy Endpoints ................................................................................................. 66 
15.1.3. 
Pharmacodynamic Endpoints .................................................................................. 67 
15.1.4. 
Pharmacokinetic Endpoints (in Subjects at Sites in Japan Only) .............................. 68 
15.2. 
Sample Size Considerations .................................................................................... 68 
15.3. 
Data Analysis Considerations ................................................................................. 68 
15.3.1. 
Analysis Populations .............................................................................................. 68 
15.3.2. 
Treatment Groups ................................................................................................... 69 
15.3.3. 
Statistical Methods ................................................................................................. 69 
15.3.3.1. 
Interim Analyses ..................................................................................................... 69 
15.3.3.2. 
Adjustment for Multiple Comparisons/Multiplicity ................................................. 69 
15.3.3.3. 
Missing Data Handling ........................................................................................... 69 
15.3.3.4. 
Windowing Conventions ........................................................................................ 69 
15.3.3.5. 
Statistical Tests ....................................................................................................... 69 
15.3.3.6. 
Common Calculations ............................................................................................ 69 
15.3.4. 
Analyses ................................................................................................................. 70 
15.3.4.1. 
Efficacy Analyses ................................................................................................... 70 
15.3.4.2. 
Biomarker Analyses ............................................................................................... 70 
15.3.4.3. 
Pharmacokinetic Analyses (Data from Sites in Japan Only) .................................... 70 
15.3.4.4. 
Safety Analyses ...................................................................................................... 71 
15.3.4.5. 
Immunogenicity Analyses....................................................................................... 71 
16. 
STUDY CONDUCT CONSIDERATIONS ............................................................ 72 
16.1. 
Posting of Information on Publicly Available Clinical Trial Registers ..................... 72 
16.2. 
Regulatory and Ethical Considerations.................................................................... 72 
16.2.1. 
Ethical Conduct of the Study .................................................................................. 72 
16.2.2. 
Independent Ethics Committees/Institutional Review Boards Approval and 
Study Compliance .................................................................................................. 72 
16.2.3. 
Ongoing Information for Independent Ethics Committees/Institutional 
Review Boards ....................................................................................................... 72 
16.2.4. 
Subject Information and Informed Consent ............................................................. 73 

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16.3. 
Quality Control (Study Monitoring) ........................................................................ 73 
16.3.1. 
Quality Assurance .................................................................................................. 74 
16.3.2. 
Confidentiality ........................................................................................................ 74 
16.3.3. 
Data Protection ....................................................................................................... 74 
16.3.4. 
Protocol Amendments and Deviations .................................................................... 75 
16.3.5. 
Delegation of Investigator Duties ............................................................................ 75 
16.3.6. 
Study and Site Closure ............................................................................................ 76 
16.4. 
Legal and Financial Aspects ................................................................................... 76 
16.4.1. 
Liability and Insurance ........................................................................................... 76 
16.4.2. 
Financial Disclosure ............................................................................................... 76 
16.5. 
Records Retention .................................................................................................. 77 
16.6. 
Use of Study Findings ............................................................................................ 77 
17. 
REFERENCES ....................................................................................................... 78 
APPENDIX 1. NEW UPDATED STUDY DESIGN FOR AMENDMENT 3 ......................... 80 
APPENDIX 2. SAMPSON CRITERIA FOR ANAPHYLAXIS ............................................. 88 
APPENDIX 3. POTENTIALLY CLINICALLY SIGNIFICANT GUIDELINES.................... 89 
 
LIST OF TABLES 
Table 1: 
Summary of Changes to the Protocol ........................................................................ 3 
Table 2: 
Serious Adverse Event Contact Information.............................................................. 5 
Table 3: 
Investigational Products .......................................................................................... 35 
Table 4: 
Schedule of Assessments for Subjects Who Participated in 
Study ATB200-03 .................................................................................................. 40 
Table 5: 
Schedule of PK Assessments for Subjects at Sites in Japan ..................................... 44 
Table 6: 
Serum Chemistry Parameters .................................................................................. 50 
Table 7: 
Hematology Parameters .......................................................................................... 51 
Table 8: 
Urinalysis Parameters ............................................................................................. 51 
Table 9: 
Guidelines for Management of Early Infusion-associated Reactions ....................... 58 
Table 10: Schedule of Assessments for Subjects Who Continue Under Protocol 
Amendment 3 ......................................................................................................... 82 
 

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5. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or Specialist Term 
Definition of Term 
6MWD 
6-minute walk distance 
6MWT 
6-minute walk test 
AE 
adverse event 
AT2221 
N-butyl-deoxynojirimycin (miglustat) 
ATB200 
recombinant human acid α-glucosidase (rhGAA) 
(cipaglucosidase alfa) 
ATB200/AT2221 
cipaglucosidase alfa co-administered with miglustat 
CK 
creatine kinase 
COVID-19 
Coronavirus disease 2019 caused by the SARS-CoV-2 virus 
CSR 
clinical study report 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EQ-5D-5L 
EuroQol 5 Dimensions-5 Levels Instrument 
ERT 
enzyme replacement therapy 
FSH 
follicle stimulating hormone 
FVC 
forced vital capacity 
Gaa 
gene encoding acid α-glucosidase (mouse protein) 
GAA 
human acid α-glucosidase 
GAA 
gene encoding human acid α-glucosidase 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GSGC 
Gait, Stairs, Gowers’ maneuver, and Chair test 
Hex4 
hexose tetrasaccharide 
IAR 
infusion-associated reaction 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgE 
immunoglobulin E 
IND 
Investigational New Drug 
IRB 
institutional review board 

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Abbreviation or Specialist Term 
Definition of Term 
IRT 
interactive response technology 
ITT 
intent-to-treat 
IV 
intravenous(ly) 
KO 
knockout 
LOPD 
late-onset Pompe disease 
MEP 
maximal expiratory pressure 
MIP 
maximal inspiratory pressure 
PD 
pharmacodynamic 
PGIC 
Physician’s Global Impression of Change 
PK 
pharmacokinetic 
PROMIS® 
Patient-reported Outcomes Measurement Information System 
REB 
research ethics board 
rhGAA 
recombinant human acid α-glucosidase 
R-PAct 
Rasch-built Pompe-specific Activity 
SAE 
serious adverse event 
SGIC 
Subject’s Global Impression of Change 
SNIP 
sniff nasal inspiratory pressure 
SUSAR 
suspected unexpected serious adverse reaction 
SVC 
slow vital capacity 
TEAE 
treatment-emergent adverse event 
TUG 
timed up and go 

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6. 
INTRODUCTION 
6.1. 
Pompe Disease 
Pompe disease (Online Mendelian Inheritance in Man #232300, also known as acid maltase 
deficiency or glycogen storage disease type II) is an autosomal recessive genetic disorder caused 
by mutations in the gene encoding human acid α-glucosidase (GAA). These mutations may result 
in complete absence or partial loss of endogenous human acid α-glucosidase (GAA) activity, 
which is responsible for the breakdown of lysosomal glycogen. The enzyme deficiency results in 
accumulation of intracellular glycogen leading to progressive disruption of cellular function, 
particularly in the heart, skeletal muscles, and diaphragm. The age at onset of clinical 
manifestations, rate of progression, and severity, including degree of organ and/or muscular 
(skeletal, respiratory, and cardiac) involvement, largely depends on the severity of the mutations 
and consequently on the residual enzyme activity (Hirschhorn and Reuser 2001; Raben, Plotz 
et al. 2002). Lower enzyme activity is generally associated with a more severe clinical course of 
the disease (Kishnani, Steiner et al. 2006). 
Pompe disease may be categorized into 2 classes: infantile-onset Pompe disease (classic and 
nonclassic) and late-onset Pompe disease (LOPD) (Leslie and Bailey 2017). 
Late-onset Pompe disease can present at any age greater than 12 months and does not present 
with clinically apparent cardiac involvement (Leslie and Bailey 2017). Late-onset Pompe disease 
is often referred to as juvenile-onset Pompe disease when occurring in the pediatric 
subpopulation of the LOPD category. Late-onset Pompe disease has a slower rate of progression 
compared with infantile-onset Pompe disease, with most patients experiencing progressive 
limb-girdle weakness and respiratory failure due to involvement of muscles in the proximal 
lower and upper limbs, paraspinal muscles, and diaphragm. Clinical manifestations include 
difficulty walking, climbing stairs, and progressive limitations of motor activities of daily living 
with progression to a need for ambulatory support followed by wheelchair dependence 
(Hirschhorn and Reuser 2001). Clinical manifestations of the disease are compounded by 
respiratory involvement, initially as sleep-disordered breathing and orthopnea (shortness of 
breath in supine position). The progressive nature of Pompe disease generally results in the use 
of invasive mechanically assisted ventilation. Biochemical abnormalities include increased level 
of serum creatine kinase (CK), a biomarker of muscle injury, and urinary hexose tetrasaccharide 
(Hex4), a biomarker of disease substrate. Life expectancy for patients with LOPD can range 
from early childhood to late adulthood, depending on the age of onset, rate of disease 
progression, the extent of respiratory muscle involvement, and the presence of co-morbidities 
(Hagemans, Janssens et al. 2004). 
Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA), 
alglucosidase alfa, became available for all patients in Europe and the US in 2006. While 
alglucosidase alfa provides initial benefit to many patients, the magnitude and duration of 
therapeutic response with continuing therapy vary among individual patients (van der Ploeg, 
Clemens et al. 2010; Schoser, Stewart et al. 2017). The current ERT, at best, may offer 
improvement in measures of muscle function, strength and respiratory function for a finite 
duration followed by slow decline in these parameters (Toscano and Schoser 2013; Wyatt, 
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The most serious tolerability issue with alglucosidase alfa is the occurrence of 
infusion-associated reactions (IARs), which, in some instances can include life-threatening 
anaphylaxis or other severe allergic responses (Lumizyme® Prescribing Information, 
August 2014; Myozyme® Summary of Product Characteristics, December 2018). Management of 
these events include dose reduction, reduced infusion rates and prolonged infusion times, and 
dose interruption or discontinuation. Premedication with antihistamines and steroids (prior to 
infusion) is also regularly used to prevent and reduce the occurrence and severity of IARs and 
hypersensitivities related to alglucosidase alfa infusion. Despite these measures, patients with 
Pompe disease may still experience IARs, and some cannot tolerate regular infusions of the 
currently approved ERT. 
Co-administration of ATB200 (rhGAA, cipaglucosidase alfa) with AT2221 (miglustat; 
N-butyl-deoxynojirimycin) (cipaglucosidase alfa/miglustat) is designed to address the limitations 
of alglucosidase alfa relating to duration of effect and tolerability issues with regard to IARs. 
Cipaglucosidase alfa has been approved in combination with miglustat in the EU, Great Britain, 
and other countries around the world for treatment of adults with LOPD, and in the US for the 
treatment of adults with LOPD who are not improving on their current ERT. 
6.2. 
Cipaglucosidase Alfa/Miglustat 
Cipaglucosidase alfa/miglustat is a novel first-in-class co-administered product approach for the 
treatment of adult and pediatric patients with LOPD. Cipaglucosidase alfa/miglustat is being 
developed for co-administration for which (1) cipaglucosidase alfa is the main active substance 
(enzyme) that is engineered for optimal targeting to lysosomes, the site of glycogen catabolism 
in affected tissues, and (2) miglustat is a co-administered enzyme stabilizer that stabilizes 
cipaglucosidase alfa from denaturation in systemic circulation, which enhances the delivery of 
the active component cipaglucosidase alfa to lysosomes. 
6.2.1. 
Cipaglucosidase Alfa 
Cipaglucosidase alfa is a next-generation rhGAA enzyme. Cipaglucosidase alfa differs 
structurally from currently approved rhGAA (alglucosidase alfa) enzyme. Based on the 
published literature, cipaglucosidase alfa matches the sequence for human alpha glucosidase but 
has important differences on its post-translational glycan structures that enable more rapid 
cellular uptake and lysosomal targeting of the enzyme. 
6.2.2. 
Miglustat 
Miglustat is an iminosugar that functions as an enzyme stabilizer of cipaglucosidase alfa. 
Because cipaglucosidase alfa is a recombinant lysosomal enzyme, it is most stable at lysosomal 
acidic pH and thus is susceptible to denaturation and enzyme inactivation at neutral blood pH 
when administered intravenously (IV). Miglustat binds to cipaglucosidase alfa and protects 
cipaglucosidase alfa from denaturation in blood. This interaction of miglustat with 
cipaglucosidase alfa results in stabilization of the cipaglucosidase alfa enzyme in the blood and 
enhancement of the pharmacokinetics of the cipaglucosidase alfa leading to a more efficient 
percentage of active enzyme being delivered to key disease-relevant tissue (ie, muscles). 
Miglustat capsules contain the same active ingredient, N-butyl-deoxynojirimycin (miglustat), as 
that in Zavesca® (Actelion Pharmaceuticals US Inc.), which is approved for the treatment of 

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adults with type I Gaucher disease (in the US and EU) and for treatment of adult and pediatric 
patients with Niemann Pick-C disease (in EU and Japan). Miglustat is administered at a lesser 
frequency (1 dose every 2 weeks) in contrast to dosing with miglustat for Gaucher disease and 
Niemann Pick-C disease (3 times daily) (see Section 11.5 for dosing for this study). 
6.3. 
Human Dosing Rationale 
The doses and regimen selected for evaluation in this study, 20 mg/kg cipaglucosidase alfa 
+ 260 mg miglustat for subjects weighing ≥ 50 kg or 195 mg miglustat for subjects weighing 
≥ 40 kg to < 50 kg every 2 weeks, is the same as that evaluated in Study ATB200-03, the study 
preceding this study. Dose selection was based on a body of evidence that includes in vitro data 
demonstrating the stabilizing effects of miglustat on the cipaglucosidase alfa enzyme, nonclinical 
pharmacokinetic (PK)/pharmacodynamic (PD) data from studies conducted in the murine gene 
encoding acid α-glucosidase (mouse protein) (ie, Gaa) knockout (KO) model, and clinical 
PK/PD, efficacy, and safety data from Phase 1/2 Study ATB200-02. 
6.3.1. 
Cipaglucosidase Alfa 
Dose selection of cipaglucosidase alfa 20 mg/kg was based on providing a comparable total 
protein dose for cipaglucosidase alfa as that approved for alglucosidase alfa, as determined by 
spectrophotometric analysis (ultraviolet absorbance 280 nm, A280), which showed comparable 
specific activity (GAA enzyme activity/mg protein/hour). Despite similar specific activities, an 
equivalent dose of 20 mg/kg administered to Gaa KO mice showed a PK profile of 
cipaglucosidase alfa distinct from alglucosidase alfa, as indicated by lower exposures. These 
lower exposures were due to faster clearance of cipaglucosidase alfa from plasma, which resulted 
in more efficient targeting and delivery of cipaglucosidase alfa into the disease-relevant muscles. 
At 20 mg/kg cipaglucosidase alfa, glycogen reduction was most effective and significantly 
improved compared with 20 mg/kg alglucosidase alfa in Gaa KO mice and was thus chosen as 
the dose to be tested in patients with Pompe disease. 
Cipaglucosidase alfa is the primary active agent with an enzymatic mechanism of action that 
specifically reduces intramuscular glycogen, the primary lysosomal storage material in LOPD. 
Cipaglucosidase alfa differs structurally from the currently approved rhGAA (alglucosidase alfa) 
based on both its amino acid sequence and post-translational glycan structures and 
phosphorylation. One of the key features that distinguishes cipaglucosidase alfa from 
alglucosidase alfa is that substantially more (~95%) of the initial cipaglucosidase alfa dose binds 
cation-independent mannose 6-phosphate receptor (CI-MPR) compared with only ~27% of 
alglucosidase alfa at equivalent enzyme concentrations. The substantially higher binding of 
cipaglucosidase alfa to the CI-MPR receptor is due to the greater bis-M6P content of 
cipaglucosidase alfa compared with alglucosidase alfa, which has 10 times higher affinity to bind 
to the receptor compared with M6P. As a result, a significantly greater amount of 
cipaglucosidase alfa is internalized into the disease-relevant muscles compared with 
alglucosidase alfa and therefore, the former is more potent. In vitro studies have demonstrated 
this by improved uptake of cipaglucosidase alfa into muscle cells as well as by substantially 
greater glycogen reduction in disease-relevant muscles of Gaa KO mice with 20 mg/kg 
cipaglucosidase alfa compared with 20 mg/kg alglucosidase alfa. In addition, in vivo studies 
have indicated that the co-administration of miglustat with cipaglucosidase alfa shows even 
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alglucosidase alfa. Therefore, a 20 mg/kg dose of cipaglucosidase alfa with miglustat is expected 
to provide improved uptake into muscle tissue than even higher doses at 40 mg/kg of 
alglucosidase alfa. 
6.3.2. 
Miglustat 
Dose selection for miglustat 260 mg was based on in vitro stability studies showing that 
miglustat at 17 µM preserves cipaglucosidase alfa catalytic activity in blood of neutral pH at 
37°C. In Gaa KO mice, oral co-administration of a dose approximating 17 µM concentration 
(10 mg/kg) administered 30 minutes before IV administration of 20 mg/kg cipaglucosidase alfa 
showed most effective glycogen reduction in skeletal muscles compared with either 
cipaglucosidase alfa alone or alglucosidase alfa. Notably, miglustat at a concentration of 17 µM 
approximates the resultant plasma concentration after oral dosing of 260 mg miglustat in the 
ongoing clinical study, ATB200-02, being conducted in patients with LOPD. Importantly, 
260 mg miglustat provided maximal duration of binding and stabilization in plasma for up to 
18 hours, with minimal duration of inhibition for up to only 4 hours in tissues (Modeling and 
Simulations to Support Dosing of cipaglucosidase alfa and miglustat for a First-In-Human Study 
in Patients with Late-Onset Pompe Disease, AMIC-PCS-102, September 2015). 
For patients who weigh ≥ 40 kg to < 50 kg, miglustat dose modification is necessary. Patients in 
this body weight category will receive 195 mg miglustat (3 × 65-mg capsules). 
Exposure-matching modeling and simulations for body weights of ≥ 40 kg to < 50 kg for the 
195 mg dose were similar to body weights of 70 kg at the 260 mg dose (ATB200 and AT2221 
Population Pharmacokinetic Simulations and Exposure Matching for Pediatric Subjects, 
February 2019). Patients who have a baseline body weight of < 50 kg, but gain weight during the 
study and reach a weight of 55 kg, will have the dose of miglustat increased to 260 mg 
(4 × 65-mg capsules). If their body weight subsequently decreases and returns to a level below 
50 kg, then the miglustat dose would be reduced to 195 mg (3 × 65-mg capsules). 
Additional information is provided in the Investigator’s Brochure. 
6.4. 
Nonclinical Studies 
Nonclinical single-dose gross tolerance and toxicokinetic studies and repeat-dose toxicology and 
toxicokinetic studies in rats and nonhuman primates with cipaglucosidase alfa alone, miglustat 
alone, and co-administered cipaglucosidase alfa/miglustat did not reveal any significant or 
adverse treatment-related changes in a variety of parameters including body weight, food 
consumption, hematology, clinical chemistry, central nervous system (rats), cardiovascular 
(nonhuman primates), and electrocardiogram (ECG) evaluation. In addition, no treatment-related 
microscopic findings were detected on histologic evaluation. Notably, in the single-dose gross 
tolerance and toxicokinetic study of miglustat in nonhuman primates, emesis was observed 
following treatment at the mid and high doses of 250 and 1000 mg/kg, but was not observed at 
the low dose of 25 mg/kg, and food consumption was not affected. In the 13-week 
co-administration toxicity study of cipaglucosidase alfa/miglustat in nonhuman primates, no 
treatment-related emesis was observed at any dose of miglustat, including the highest tested dose 
of 175 mg/kg. No other overt signs of toxicity were noted in any of the single- or repeat-dose 
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6.5. 
Clinical Studies 
Study ATB200-02 is an ongoing Phase 1/2 first-in-human study of safety, tolerability, PK, PD, 
and efficacy of cipaglucosidase alfa/miglustat in subjects with LOPD. The study is being 
conducted in 4 stages: single-ascending doses of cipaglucosidase alfa (Stage 1, 6 weeks), 
multiple-ascending doses of miglustat co-administered with cipaglucosidase alfa (Stage 2, 
12 weeks), extended treatment at the selected doses (Stage 3, 2 years), and long-term extension 
(Stage 4, until approval). 
Refer to the current Investigator’s Brochure (IB) for updated clinical information. 
6.6. 
Summary of Known and Potential Risks and Benefits 
Based on efficacy and safety information in the Investigator’s Brochure, the benefit-risk balance 
of cipaglucosidase alfa/miglustat remains positive overall. Cipaglucosidase alfa/miglustat has 
demonstrated clinically significant benefits in the treatment of Pompe disease, and no important 
risks have been identified that would preclude the use of cipaglucosidase alfa/miglustat. Mild to 
moderate IARs have been identified in ongoing clinical studies and are manageable with 
reduction or temporary stopping of infusion and premedication with corticosteroids, 
antihistamines, and acetaminophen. No life-threatening or fatal IARs have been observed in 
clinical studies to date. As with any investigational new drug (IND) or research study procedure, 
there are risks that are not known that may be serious and may even cause death. The most up to 
date information regarding efficacy, safety, and benefit-risk assessment for cipaglucosidase 
alfa/miglustat can be found in the current Investigator’s Brochure. 
Cipaglucosidase alfa/miglustat has proven overall to be generally safe and relatively well 
tolerated. Alternative treatments provide initial benefit to patients with Pompe disease. The 
magnitude and duration of therapeutic response with continuing therapy varies among individual 
subjects and, at best, may offer improvement in measures of muscle function, strength, and 
respiratory function for a finite duration, ie, 2 to 3 years in most subjects, followed by a slow 
decline in these parameters. These alternative treatments may themselves be associated with 
significant risks. A monthly review for safety signals is part of routine pharmacovigilance. 
The strength of the current benefit-risk analysis is based on the safety pool of data from a variety 
of sources (clinical study, literature, and independent registries) and in various geographies 
(eg, EU, Australia, and US) while the mean duration of treatment is approaching 36 months. 
Weakness of the data is primarily based on the small number of subjects in the clinical study 
described. There are no specific studies that target specific subpopulations of patients such as 
elderly, or subpopulations. Uncertainties exist over the long-term safety profile. 
Study participants may not experience any benefit from participating in this study. However, 
potential benefits include stabilization or improvement in the signs and symptoms of Pompe 
disease and the positive health effects of regular surveillance by a physician. In addition, study 
participation provides the opportunity to contribute data relevant and necessary for continued 
advancement in the treatment of Pompe disease. In light of the progressive nature of Pompe 
disease and the benefits observed in adults with LOPD to date, the potential benefits justify the 
risks and inconveniences of clinical trial participation. The sponsor acknowledges that these 
inconveniences include frequent travel to the study site with associated impact on attendance at 
work and/or school; the discomfort of study procedures, such as blood draws; and the need to 

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follow other study requirements, such as adequate birth control for females of child‑bearing 
potential. However, the sponsor has made efforts to limit this impact by allowing for at‑home 
administration of study medication (if permitted locally and deemed clinically appropriate based 
on criteria outlined in the protocol) and minimizing the number of visits with full study 
assessments. Finally, study participants are informed at the time of consent that if at any time 
they do not wish to continue with the study, eg if the risks or inconveniences become too 
onerous, they may withdraw without any adverse impact on their ongoing care by their 
physician. 
Refer to the current IB for updated information. 
6.7. 
Study Population 
This is an open-label extension study for adult subjects with LOPD who completed 
Study ATB200-03. For this amendment, subjects may continue in this study until commercial 
cipaglucosidase alfa/miglustat becomes available in their country as a treatment for Pompe 
patients. 

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7. 
STUDY OBJECTIVES 
The final analysis will be performed for the final CSR based on a data cutoff date of 
31 December 2024 with the study objectives below. The study objectives upon approval of this 
amendment are presented in Appendix 1, Section 7. 
7.1. 
Primary Objective 
The primary objective of this study is to assess the long-term safety and tolerability of 
cipaglucosidase alfa/miglustat co-administration. 
7.2. 
Secondary Objectives 
The secondary objectives of this study are as follows: 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on ambulatory function, as measured by the 6-minute walk test (6MWT) 
• to assess the long-term efficacy cipaglucosidase alfa/miglustat co-administration on 
pulmonary function, as measured by sitting forced vital capacity (FVC) (% predicted) 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on muscle strength 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on health-related patient-reported outcomes 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on motor function 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on overall clinical impression, as assessed by both physician and subject 
• to assess the long-term efficacy of cipaglucosidase alfa/miglustat co-administration 
on measures of pulmonary function other than FVC (% predicted) 
• to assess the long-term effect of cipaglucosidase alfa/miglustat co-administration on 
biomarkers of muscle injury and disease substrate 
• to assess the immunogenicity of cipaglucosidase alfa/miglustat co-administration 
• to characterize the pharmacokinetics of cipaglucosidase alfa and miglustat using 
plasma total GAA protein level by signature peptide and plasma miglustat 
concentration assays in subjects at sites in Japan only 

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8. 
INVESTIGATIONAL PLAN 
8.1. 
Study Design 
This is a multicenter, international, open-label extension study of cipaglucosidase alfa/miglustat 
in adult subjects with LOPD who completed Study ATB200-03. 
The purpose of this amendment is to continue collecting long-term safety and efficacy data on 
LOPD subjects treated with cipaglucosidase alfa/miglustat while decreasing some of the burden 
on those subjects taking part, and continuing to provide treatment where regulatory approval has 
not yet been granted or the product is not yet commercially available. Subjects may continue in 
this study until commercial cipaglucosidase alfa/miglustat becomes available in their country as 
a treatment for Pompe patients. The final analysis will be performed for the final CSR based on a 
data cutoff date of 31 December 2024. Upon approval of this amendment, any subjects 
continuing in the study will follow the updated Schedule of Assessments in Table 10. 
For subjects who participated in Study ATB200-03, the first infusion visit in this study should be 
scheduled approximately 2 weeks after the last visit in Study ATB200-03 in an effort to ensure 
continued administration of study drug on the same schedule with no gap between studies. 
Infusion visits for administration of study drug will be scheduled every 2 weeks throughout the 
study; assessments (eg, clinical laboratory tests) for monitoring of initial safety will be 
performed at these infusion visits for the first 6 weeks of the study. During the conduct of the 
study, the SARS-CoV-2 (COVID-19) pandemic emerged and impeded the conduct of site visits 
and laboratory testing due to quarantines, travel restrictions, and risk of infection. With the 
intention of maintaining regular infusions, home infusions will be allowed prior to completing 
Week 12 wherever possible for subjects who may be eligible (see Section 12.2.2). Study visits 
that include efficacy, safety, and other assessments will be scheduled approximately every 
3 months for the first 6 months, then every 6 months thereafter. These visits may occur over 
2 days, provided all study assessments and procedures (with the exception of PK sample 
collection) are performed before administration of study drug. If a visit was missed due to 
COVID-19-related quarantines, travel restrictions, and risk of infection, it should be recorded as 
such in the Interactive Response Technology (IRT) system and electronic data capture (EDC) 
system. A reason for the missed visit should be entered into the EDC as COVID-19 related. The 
relevant institutional review boards (IRBs), independent ethics committees (IECs), and REBs 
should be notified of any deviations from the protocol. If infusions were missed near the 
scheduled assessments at Week 12, Week 26, or at any of the study visits scheduled every 
26 weeks after Week 26, it should be communicated with Amicus on a case-by-case basis to 
determine whether catch-up infusions are needed and how many catch-up infusions are needed 
prior to the study assessments. 
Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function 
(6MWT), motor function tests (Gait, Stairs, Gowers’ maneuver, and Chair [GSGC] test and 
timed up and go [TUG] test), muscle strength (manual muscle testing and quantitative muscle 
testing), and pulmonary function tests (FVC, slow vital capacity [SVC], maximal inspiratory 
pressure [MIP], maximal expiratory pressure [MEP], and sniff nasal inspiratory pressure 
[SNIP]). Patient-reported outcomes include Rasch-built Pompe-specific Activity (R-PAct) Scale, 
EuroQol 5 Dimensions-5 Levels Instrument (EQ-5D-5L), Patient-reported Outcomes 
Measurement Information System (PROMIS®) instruments for physical function, fatigue, 

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dyspnea, and upper extremity, and Subject’s Global Impression of Change (SGIC). The 
Physician’s Global Impression of Change (PGIC) will also be performed. Pharmacodynamic 
assessments include measurement of biomarkers of muscle injury (CK) and disease substrate 
(urinary Hex4). Blood samples for PK assessment of total GAA protein and miglustat 
concentration in plasma will be collected from subjects at sites in Japan only. Safety assessments 
include monitoring of AEs, including IARs, clinical laboratory tests (chemistry, hematology, and 
urinalysis), vital signs, physical examinations including weight, ECGs, and immunogenicity. 
Concomitant medications and nondrug therapies will also be recorded. 
For subjects continuing in the study after approval of this amendment, updated efficacy and 
safety assessments are provided in Appendix 1, Section 8.1. 
8.2. 
Duration of Study 
The study will consist of a treatment period that lasts until one of the following conditions apply: 
• the product is approved and commercialized for use in the investigational study 
population, or 
• cipaglucosidase alfa/miglustat is rejected by the regulatory authority in the subject’s 
local country as an approved treatment for Pompe disease, or 
• the sponsor decides to continue to provide cipaglucosidase alfa/miglustat via a 
post-trial access mechanism, or 
• the subject is withdrawn or withdraws consent, or 
• the sponsor decides to end the study. 
8.3. 
Criteria for Termination of the Study 
The study may be terminated by the sponsor if there is evidence suggesting that safety risks 
associated with cipaglucosidase alfa/miglustat treatment outweigh the potential benefits. 
8.4. 
Definition of the End of Study 
End of study is defined as the date of the last subject’s last visit. The final analysis will be 
performed for the final CSR based on a data cutoff date of 31 December 2024. Any data 
collected after this date will be provided as an addendum to the final CSR when all subjects have 
completed the study or have been withdrawn from the study. Upon approval of this amendment, 
subjects who remain in the study will follow the Schedule of Assessments in Appendix 1 
(Table 10). 
8.5. 
Definition of Study Completer 
A study completer is defined as a subject who has fulfilled both of the following requirements: 
• completion of study treatment, defined as continuing to receive treatment as a 
participant in the ATB200-07 study until the study ends or until the subject transitions 
to locally approved and commercially available cipaglucosidase alfa/miglustat or 
another post-trial access mechanism 

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8.6. 
Discussion of Study Design, Including Choice of Control Groups 
This is an open-label extension study to assess the long-term safety of cipaglucosidase 
alfa/miglustat and has no control group. Although efficacy will be assessed, it is not a primary 
objective. 

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9. 
SUBJECT SELECTION AND WITHDRAWAL CRITERIA 
9.1. 
Number of Subjects 
The maximum sample size for this study is based on the number of subjects who complete 
Study ATB200-03, estimated to be approximately 110 subjects at up to approximately 59 sites 
globally. 
9.2. 
Eligibility Criteria 
9.2.1. 
Subjects Who Participated in Study ATB200-03 
Subjects who participated in Study ATB200-03 must meet all of the inclusion criteria and none 
of the exclusion criteria to be eligible to participate in the study. 
9.2.1.1. 
Inclusion Criteria 
1. Subject must provide signed informed consent prior to any study-related procedures 
being performed. If the subject is under 20 years of age, the subject must provide written 
informed consent. In Japan, the subject’s parental guardian (or legal representative) must 
also sign the informed consent form. 
2. Subjects must have completed Study ATB200-03. 
Note: Subjects who were forced to withdraw from Study ATB200-03 for a logistical 
reason not related to the efficacy or safety of cipaglucosidase alfa/miglustat 
(eg, hospitalization for a car accident, COVID-19 pandemic, or emergency surgery) and 
which resulted in several consecutive missed doses may be eligible to participate in this 
study upon approval by the Amicus medical monitor. 
3. Female subjects of childbearing potential and male subjects must agree to use medically 
accepted methods of contraception during the study and for 90 days after the last dose of 
study drug. 
9.2.1.2. 
Exclusion Criteria 
1. Subject plans to receive gene therapy or participate in another interventional study for 
Pompe disease. 
2. Subject has a hypersensitivity to any of the excipients in cipaglucosidase alfa or 
miglustat, or has a medical condition or any other extenuating circumstance that may, in 
the opinion of the investigator or medical monitor, pose an undue safety risk to the 
subject or may compromise his/her ability to comply with or adversely impact protocol 
requirements. This includes clinical depression (as diagnosed by a psychiatrist or other 
mental health professional) with uncontrolled or poorly controlled symptoms. 
3. Subject, if female, is pregnant or breastfeeding. 
4. Subject, whether male or female, is planning to conceive a child during the study. 

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9.3. 
Withdrawal Criteria 
Subjects may withdraw or be withdrawn from the study for any reason, including, but not limited 
to, the following: 
• at their own request 
• if, in the investigator’s opinion, continuation in the study would be detrimental to the 
subject’s well-being 
Note: Subjects with serious adverse events (SAEs) of anaphylaxis to cipaglucosidase 
alfa must be withdrawn from the study. 
• if, in the investigator’s opinion, there is a lack of efficacy for the subject 
• persistent noncompliance with study requirements, such as failure to comply with the 
study visit schedule, in the judgment of the investigator and/or medical monitor 
• persistent noncompliance with study drug or failure to return to the study site for 
infusion visits, in the judgment of the investigator and/or medical monitor 
• inability to contact subject (ie, subject is lost to follow-up) 
• pregnancy (female subjects) 
• planning to conceive a child (male or female subjects) 
• sponsor decision to terminate the study 
In all cases, the reason for withdrawal and the date of withdrawal must be recorded in the 
electronic case report form (eCRF) and in the subject’s medical records. 
Subjects who withdraw will be requested to complete the Early Termination Visit. The 
investigator will make every effort to contact withdrawing subjects and schedule the early 
termination assessments. Upon study completion or subject discontinuation, subjects who are 
confirmed positive for anti-rhGAA antibodies will complete follow-up immunological testing for 
up to 12 months after the last dose of study drug (ie, at 6 months and 12 months) or until they 
begin treatment with an investigational therapy or an ERT that is approved by the local health 
authority and is commercially available (see 12.2.6). 
9.4. 
Subjects of Reproductive Potential 
Subjects must be willing to apply highly effective contraception during the study and through the 
duration as defined below and for 90 days after the final dose of study treatment. 
The allowed methods of contraception described in the following text are only effective when 
used consistently, correctly, and in accordance with the product label. For Japanese subjects, 
only approved contraceptive measures in Japan are considered as effective measures. The 
investigator is responsible for ensuring subjects understand how to properly use these methods of 
contraception. A highly effective birth control is defined as one that results in a low failure rate 
(ie, < 1% per year) when used consistently and correctly. 

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Women of child-bearing potential are defined as all women physiologically capable of becoming 
pregnant, ie, fertile, following menarche and until becoming post-menopausal unless 
permanently sterile. Highly effective methods of contraception include the following: 
• combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: oral, intravaginal*, transdermal* 
• progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable*, implantable* 
• intrauterine device 
• intrauterine hormone-releasing system 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
Note: * Indicates products not approved in Japan. 
Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. 
Note: Women are considered post-menopausal and not of child-bearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age 
appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with a 
serum FSH level > 40 mIU/mL and estradiol < 20 pg/mL, or have had surgical bilateral 
oophorectomy, only when the reproductive status of the woman has been confirmed by 
follow-up hormone level assessment and she is considered not of child-bearing potential. 
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Male subjects and their partners must use highly effective methods of contraception (ie, condom 
in male subjects and highly effective contraception, as listed previously in this section, in their 
female partners) for the entire duration of the study and continue to use contraception and refrain 
from fathering a child for 90 days following the study treatment. 
In the event of pregnancy in a female subject, study drug must be discontinued. Pregnancies 
occurring during study participation (female subject or a female partner of a male subject) must 
be reported to Amicus and followed as described in Section 13.4. 

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10. 
TREATMENT OF SUBJECTS 
Subjects will receive cipaglucosidase alfa/miglustat as follows: miglustat 260 mg (4 × 65-mg 
oral capsules) for subjects weighing ≥ 50 kg or miglustat 195 mg (3 × 65-mg oral capsules) for 
subjects weighting ≥ 40 kg to < 50 kg, followed approximately 1 hour later by cipaglucosidase 
alfa 20 mg/kg (reconstituted lyophilized drug product, 105 mg/vial), administered over a 4-hour 
IV infusion. The cipaglucosidase alfa/miglustat combination regimen will be administered every 
2 weeks. Subjects are required to fast at least 2 hours before and 2 hours after administration of 
miglustat. 
Study drug will be administered every 2 weeks at the study site. After 3 months in the study 
without any moderate to severe IARs, subjects may be eligible for administration of study drug 
at their home (see Section 12.2.2). In countries or at sites where the administration of 
alglucosidase alfa is reserved for hospital use, however, all study drug will be administered in a 
hospital setting. 
Cipaglucosidase alfa and miglustat will be administered under the supervision of study site 
personnel; therefore, treatment compliance will be calculated using study drug administration 
records. 

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11. 
STUDY DRUG MATERIALS AND MANAGEMENT 
11.1. 
Study Drug 
Study drug is defined in this protocol as cipaglucosidase alfa/miglustat, cipaglucosidase 
alfa/miglustat, and a combination of these. 
Cipaglucosidase alfa (rhGAA) functions as ERT. Miglustat (N-butyl-deoxynojirimycin) is an 
iminosugar that functions as an enzyme stabilizer of rhGAA. Table 3 provides details on the 
investigational products. 
Table 3: 
Investigational Products 
Product Name 
Cipaglucosidase Alfa 
Miglustat 
Dosage Form 
Lyophilized powder for IV infusion 
Hard gelatin capsule 
Unit Dose 
15 mg/mL 
65 mg 
Route of Administration 
IV infusion 
Oral 
Physical Description 
Sterile, nonpyrogenic, white to 
off-white lyophilized cake or powder 
supplied in single-use, clear 20-mL 
(cc) glass vials 
White, size 2, hard gelatin 
capsules supplied in 40-cc HDPE 
bottles or size 2, hard gelatin 
capsules with a gray opaque cap, 
white opaque body, printed with 
“AT2221” in black ink on the 
body, supplied in 40-cc HDPE 
bottles 
Excipients 
Sodium citrate dihydrate,  
citric acid monohydrate,  
mannitol,  
polysorbate-80 
Microcrystalline cellulose, 
pregelatinized starch,  
sucralose, 
magnesium stearate,  
colloidal silicon dioxide 
Manufacturer 
WuXi Biologics Co., Ltd 
108 Meiliang Rd 
Mashan, Binhu District, 
WuXi, China 
Alcami 
1726 N 23rd St 
Wilmington, NC 28405 
USA 
Abbreviations: HDPE = high density polyethylene; IV = intravenous; USA = United States of America 
11.2. 
Study Drug Packaging and Labeling 
Miglustat (65 mg oral capsule) will be supplied by Amicus to sites or the central pharmacy used 
for the home infusion program as hard gelatin capsules in high density polyethylene bottles and 
will be administered orally. 
Cipaglucosidase alfa (105 mg/vial) will be supplied by Amicus to sites or the central pharmacy 
used for the home infusion program as a lyophilized powder in glass vials and will be 
administered by IV infusion upon reconstitution with sterile water for injection and followed by 
dilution with 0.9% sodium chloride for injection prior to administration. Sterile water for 
injection and 0.9% sodium chloride for injection will be supplied by the study sites or central 
pharmacy used for the home infusion program. 

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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. All labels will comply with legal requirements of each country. 
11.3. 
Study Drug Storage 
Sites and the central pharmacy used for the home infusion program will be instructed to store 
miglustat 65-mg oral capsules according to the conditions identified on the labels of each study 
drug, at room temperature (15°C to 25°C or 59°F to 77°F), with excursions permitted down to 
2°C or 36°F and up to 40°C or 104°F for up to 20 days in a secure area, free from environmental 
extremes, and with restricted access. 
Sites and the central pharmacy used for the home infusion program will be instructed to store 
cipaglucosidase alfa lyophilized powder vials according to the conditions identified on the study 
drug label, at cold temperature (2°C to 8°C or 36°F to 46°F), with excursions of up to 7 days 
permitted down to -20°C or -4°F and up to 25°C or 77°F in a secure area, free from 
environmental extremes, and with restricted access. 
Temperature logs must be maintained for the duration of the study. The temperature of the 
refrigerator where cipaglucosidase alfa is stored and the temperature of the storage room (or 
cabinet) where the miglustat are stored must be recorded for each working day of the week the 
pharmacy personnel (or designated study personnel) 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 the institution’s 
standard maintenance policy. 
The study drugs are to be stored only at the site(s) listed on Form FDA 1572 or Statement of 
Foreign Investigator form for non-US sites. Study drug is to be dispensed only to subjects who 
have provided written informed consent and have met all entry criteria. 
11.4. 
Study Drug Preparation 
Instructions for preparation of oral product and infusion as well as the volume and rate of 
infusion will be provided in the pharmacy manual. 
11.5. 
Administration 
11.5.1. 
Cipaglucosidase Alfa 
The dose of cipaglucosidase alfa, 20 mg/kg, is based on body weight and will be based on the 
last available body weight value in the IRT system. Weight will be entered into the IRT system 
at the Baseline Visit, Week 12, Week 26, and every 26 weeks thereafter for calculation of 
cipaglucosidase alfa dose. 
Cipaglucosidase alfa does not contain any preservatives. Vials are single-use only. Reconstituted 
vials should be retained at the site or the central pharmacy for the home infusion program until 
the monitor checks accountability. 

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Cipaglucosidase alfa is to be administered every 2 weeks as an approximate 4-hour IV infusion. 
Changes in any premedications, dose, rate, or duration of infusion due to safety or tolerability 
issues will be documented. The total volume of infusion is determined by the subject’s body 
weight. Instructions for preparation for infusion and the volume and rate of infusions will be 
provided in the pharmacy manual. Reconstitution of cipaglucosidase alfa should be performed by 
qualified study personnel (eg, pharmacist or pharmacy technician or nurse under physician 
supervision). Intravenous administration of cipaglucosidase alfa should be performed by 
qualified study personnel. Subjects should be carefully monitored during and after the first 
3 infusions (Section 12.2.2). Any delegation of this responsibility must follow Section 16.3.5. 
Rate and duration of infusion must be constant for each infusion. 
11.5.2. 
Miglustat 
The dose of miglustat is 260 mg (4 × 65-mg oral capsules) for subjects weighing ≥ 50 kg and 
195 mg (3 × 65-mg oral capsules) for subjects weighing ≥ 40 kg to < 50 kg. 
Miglustat is administered orally, approximately 1 hour before cipaglucosidase alfa infusion. 
Subjects will take 3 or 4 capsules of miglustat, depending on their body weight. Subjects should 
fast for at least 2 hours before and 2 hours after administration of miglustat. Fasting is defined as 
nothing by mouth except water; this includes prescription or over-the-counter medications, 
vitamins, or herbal supplements other than premedications for administration of cipaglucosidase 
alfa. If a medication is considered necessary for the health of the subject, approval must be 
obtained from the medical monitor unless in case of emergency. Therefore, subjects should 
arrive at the clinic at least 1 hour prior to the start of the cipaglucosidase alfa infusion to receive 
miglustat. 
If a subject has received miglustat on a dosing day but then is unable to receive the infusion of 
cipaglucosidase alfa, the subject may be re-dosed with miglustat at least 24 hours later, prior to 
their rescheduled infusion of cipaglucosidase alfa. 
11.6. 
Randomization and Blinding 
This is an open-label study with no randomization. However, treatment assignment from 
Study ATB200-03 must remain blinded until that study is complete and treatment assignments 
are unblinded for analysis. Therefore, an unblinded monitor will be employed to review select 
laboratory results that could potentially unblind a subject’s treatment assignment. 
11.7. 
Study Drug Accountability 
In accordance with local regulatory requirements, the investigator, designated site personnel, 
head of the medical institution (where applicable), or certified mobile research nurse for home 
infusions must document the amount of study drug dispensed and/or administered to study 
subjects, and the amount received from and returned to Amicus (or designee), where applicable. 
Product accountability records must be maintained throughout the course of the study. 

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11.8. 
Study Drug Handling and Disposal 
The investigator must keep an accurate record/log of the quantities of study drug dispensed and 
administered to each subject. The monitor will periodically check the supplies of study drugs 
held at the site or central pharmacy used for the home infusion program to verify accountability 
of all study drugs used and to verify the drug accountability logs are completed and maintained 
in the investigator study file. The monitor will return all original containers of study drugs, 
whether empty or containing used or unused study drugs, to Amicus or their designee for 
destruction. Sites and certified mobile research nurses for home infusions may not destroy study 
drugs on site unless Amicus has provided prior written approval. 
11.9. 
Prohibited Medications 
Use of the following medications is prohibited during treatment with study drug: 
• miglitol (eg, Glyset®) 
• nonstudy miglustat (eg, Zavesca) 
• approved ERT (eg, alglucosidase alfa or avalglucosidase alfa) after treatment with 
cipaglucosidase alfa/miglustat has begun 
• acarbose (eg, Precose® or Glucobay®) 
• voglibose (eg, Volix®, Vocarb®, or Volibo®) 
• oral anabolic steroid or derivative 
• any investigational/experimental drug 
Subjects who are taking β2-receptor agonists or nonselective β-blockers (eg, propranolol, 
nadalol, carvedilol) before Day 1 must maintain the same dose as was received during 
Study ATB200-03 for the duration of this study. Use of inhaled β-2 agonists and/or single uses 
of epinephrine (eg, for treatment of an infusion-associated reaction) are permitted. 

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12. 
STUDY PARAMETERS AND PROCEDURES 
12.1. 
Schedule of Assessments 
A Schedule of Assessments showing each study assessment and procedure along with the 
scheduled time of occurrence is provided for subjects who participated in Study ATB200-03 
(Table 4). 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. 
For subjects continuing in the study after approval of this amendment, an updated Schedule of 
Assessments is provided in Appendix 1 (Table 10). 
Visits may occur over 2 days; if assessments are not able to be completed in 2 days, an additional 
day may be scheduled. Once established, every effort should be made to maintain the order of 
procedures, approximately at the same time of day, at each study visit throughout the study, 
regardless of the number of days that are used for the visit. 

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Table 4: 
Schedule of Assessments for Subjects Who Participated in Study ATB200-03 
 
 
Treatment 
Follow-up 
Study Visit 
Baselinea 
Day 1b 
Infusion Visits 
(Every 2 Weeks 
Through 
EOS/ET) 
Weeks 
2, 4, 6 
Weeks 12, 26, 
and then 
Every 26 Weeksc 
EOS/ 
ET 
≥ 30 Days 
After Last 
Dose 
Visit Window (Days) 
— 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Administrative 
Informed consent (12.2.1) 
X 
 
 
 
 
 
 
Eligibility criteria (9.2.1) 
X 
X 
 
 
 
 
 
Demographics (12.3.1) 
X 
 
 
 
 
 
 
Schedule next visit 
X 
X 
X 
X 
X 
X 
 
Clinical Assessment 
Medical history (12.3.2) 
X 
 
 
 
 
 
 
Prior/concomitant medications and nondrug 
therapies (12.3.3) 
X 
X 
X 
X 
X 
X 
X 
Complete PE (12.3.4) 
X 
 
 
 
 
X 
 
Brief PE (12.3.4) 
 
 
 
X 
X 
 
 
Vital signs (12.3.6) 
X 
X 
X 
X 
X 
X 
 
Weightd (12.3.5) 
X 
 
 
 
X 
X 
 
Height (12.3.5) 
X 
 
 
 
 
 
 
AEs/SAEs, including IARs (13) 
X 
X 
X 
X 
X 
X 
X 

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Table 4: 
Schedule of Assessments for Subjects Who Participated in Study ATB200-03 (Continued) 
 
 
Treatment 
Follow-up 
Study Visit 
Baselinea 
Day 1b 
Infusion Visits 
(Every 2 Weeks 
Through 
EOS/ET) 
Weeks 
2, 4, 6 
Weeks 12, 26, 
and then 
Every 26 Weeksc 
EOS/ 
ET 
≥ 30 Days 
After Last 
Dose 
Visit Window (Days) 
— 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Subject/Physician-reported Outcomese 
R-PAct Scale (12.3.8) 
X 
 
 
 
X 
X 
 
PROMIS instruments for physical function, 
fatigue, dyspnea, upper extremity (12.3.8) 
X 
 
 
 
X 
X 
 
EQ-5D-5L (12.3.8) 
X 
 
 
 
X 
X 
 
PGIC (12.3.9) 
 
 
 
 
X 
X 
 
SGIC (12.3.8) 
 
 
 
 
X 
X 
 
Laboratory Assessments 
12-lead ECG (12.3.10) 
X 
 
 
 
X 
X 
 
Serum chemistry, hematology (12.3.11.1) 
X 
 
 
X 
X 
X 
 
Anti-rhGAA antibodies (total and 
neutralizing) (12.3.12) 
X 
 
 
X 
X 
X 
 
IgE (12.3.12) 
X 
 
See Section 12.3.12. 
Urine pregnancy testf (12.3.11.2) 
X 
X 
X 
X 
X 
X 
 
Urinary Hex4 (12.3.14) 
X 
 
 
X 
X 
X 
 
Urinalysis (12.3.11.1) 
X 
 
 
X 
X 
X 
 

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Table 4: 
Schedule of Assessments for Subjects Who Participated in Study ATB200-03 (Continued) 
 
 
Treatment 
Follow-up 
Study Visit 
Baselinea 
Day 1b 
Infusion Visits 
(Every 2 Weeks 
Through 
EOS/ET) 
Weeks 
2, 4, 6 
Weeks 12, 26, 
and then 
Every 26 Weeksc 
EOS/ 
ET 
≥ 30 Days 
After Last 
Dose 
Visit Window (Days) 
— 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Pulmonary Function Tests 
MIP, MEP, SNIP (12.3.16) 
X 
 
 
 
X 
X 
 
FVC, SVC (sitting, supine) (12.3.16) 
X 
 
 
 
X 
X 
 
Motor Function Assessments 
TUG (12.3.17) 
X 
 
 
 
X 
X 
 
GSGC (12.3.17) 
X 
 
 
 
X 
X 
 
6MWT (12.3.18) 
X 
 
 
 
X 
X 
 
Muscle Strength 
Manual muscle strength (MRC) (12.3.19) 
X 
 
 
 
X 
X 
 
Quantitative muscle strength (hand-held 
dynamometer) (12.3.19) 
X 
 
 
 
X 
X 
 

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Table 4: 
Schedule of Assessments for Subjects Who Participated in Study ATB200-03 (Continued) 
 
 
Treatment 
Follow-up 
Study Visit 
Baselinea 
Day 1b 
Infusion Visits 
(Every 2 Weeks 
Through 
EOS/ET) 
Weeks 
2, 4, 6 
Weeks 12, 26, 
and then 
Every 26 Weeksc 
EOS/ 
ET 
≥ 30 Days 
After Last 
Dose 
Visit Window (Days) 
— 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Study Drug Administration 
Miglustat (10) 
 
Every 2 weeks 1 hour before infusion of cipaglucosidase alfa 
 
Cipaglucosidase alfa (10) 
 
Every 2 weeks 
 
Abbreviations: 6MWT = 6-minute walk test; AE = adverse event; ECG = electrocardiogram; EOS = end of study; EQ-5D-5L = EuroQol 5 Levels-5 Dimensions 
Instrument; ERT = enzyme replacement therapy; ET = early termination; FVC = forced vital capacity; GAA = human acid α-glucosidase; GSGC = Gait, Stairs, 
Gowers’ maneuver, and Chair test; Hex4 = hexose tetrasaccharide; IAR = infusion-associated reaction; IgE = immunoglobulin E; IRT = interactive response 
technology; MEP = maximal expiratory pressure; MIP = maximum inspiratory pressure; MRC = Medical Research Council; PE = physical examination; 
PGIC = Physician’s Global Impression of Change; PK = pharmacokinetic; PROMIS = Patient-reported Outcomes Measurement Information System; 
rhGAA = recombinant human acid α-glucosidase; R-PAct = Rasch-built Pompe-specific Activity; SAE = serious adverse event; SGIC = Subject’s Global 
Impression of Change; SNIP = sniff nasal inspiratory pressure; SVC = slow vital capacity; TUG = timed up and go 
a Baseline Visit is for subjects who did not complete Week 52 in Study ATB200-03. 
b Day 1 Visit is to be scheduled approximately 2 weeks after the last administration of study drug in Study ATB200-03. Except for study drug administration and 
scheduling the next visit, all study procedures/assessments at the Day 1 Visit are to be performed only if results are not available from the last study visit in 
Study ATB200-03. If a subject has a change in the use of an assistive device that was used to perform the 6MWT during Study ATB200-03, then the 6MWT 
must be repeated at the Visit. 
c After Week 26, study visits will be scheduled every 26 weeks until 31 December 2027 or until study termination by the sponsor. 
d Weight will be entered into the IRT system at the Baseline Visit, Week 12, Week 26, and every 26 weeks thereafter for calculation of cipaglucosidase alfa 
dose. 
e Subjects are to complete patient-reported outcome questionnaires before any other study assessment, if the questionnaires are available in that subject’s 
language. 
f Urine pregnancy tests are performed only for female subjects of childbearing potential. If the urine pregnancy test has a positive result, study drug will not be 
administered and a confirmatory serum pregnancy test will be performed. 

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Table 5: 
Schedule of PK Assessments for Subjects at Sites in Japan 
Abbreviations: EOS = end of study; ET = early termination; GAA = human acid α-glucosidase; PK = pharmacokinetic 
a Baseline efficacy assessments will be performed during screening, and baseline safety assessments will be performed on Day 1. 
b For ERT-experienced subjects, Day –15 of the Screening Visit will be scheduled 1 to 2 days before the subject’s next alglucosidase alfa infusion. For 
ERT-naïve subjects, the Screening Visit may be scheduled anytime between Day –30 and Day –15. 
c After Week 52, study visits will be scheduled every 26 weeks until 31 December 2027 or until study termination by the sponsor. 
d PK samples will be collected only in subjects at Japanese sites at either Week 2, 4, or 6 and at Week 52 only. Sparse blood samples will be collected for PK 
analysis at the time points specified in Section 12.3.13. 
 
Screening/Baseline 
(Day –30 to Day –1)a 
Treatment 
Follow-up 
Study Visit 
Day  
–15b 
Day  
–14 
Day  
1 
Infusion Visits 
(Every 2 Weeks 
Through Week 52) 
Weeks 
2, 4, 6 
Weeks 12, 26, 
52, and then 
Every 26 Weeksc 
EOS/ 
ET 
≥ 30 Days 
After Last 
Dose 
Visit Window (Days) 
— 
— 
— 
± 3 
± 3 
± 3 
± 3 
± 3 
PK Assessments 
PK blood sampling (total GAA protein, 
miglustat)d (Section 12.3.13) 
 
 
 
 
X 
X 
 
 

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12.2. 
Additional Details on Study Visits 
For subjects continuing in the study after approval of this amendment, please refer to Appendix 1 
for additional details on study visits. 
12.2.1. 
Day 1 for Subjects who Participated in Study ATB200-03 
For subjects who participated in Study ATB200-03, the Day 1 Visit should be scheduled 
approximately 2 weeks after the last visit in Study ATB200-03 in an effort to ensure continued 
administration of study drug on the same schedule with no gap between studies and may occur 
over 2 days. 
Administration of informed consent and confirmation of eligibility criteria will occur at the final 
visit in Study ATB200-03. Study personnel must confirm that these procedures were performed 
before any other study assessments are performed. 
Subjects will also be registered using an IRT system at the last study visit in Study ATB200-03 
to allow sufficient lead time for the first drug shipment. All subsequent shipments will be sent 
automatically through IRT system. Refer and comply with detailed guidelines in the IRT manual. 
Any subjects who participated in Study ATB200-03, signed informed consent for this study, but 
did not receive at least 1 dose of study drug will have the following information entered into the 
electronic data capture system: reason for not being started on study drug, demographic 
information, informed consent, and inclusion/exclusion pages. 
Day 1 is the first day of open-label study drug administration. Results from the last visit in 
Study ATB200-03 will serve as baseline values for this study. If a result from Study ATB200-03 
is missing, that assessment will be performed at the Baseline Visit before open-label study drug 
is administered. 
Japanese subjects who have undergone PK sample collection at the Week 52 visit in 
Study ATB200-03 will have their initial PK sample in this study collected at any of the Week 2, 
4, or 6 visits. 
12.2.2. 
Infusion Visits and Home Infusion Visits 
Infusion visits will be scheduled every 2 weeks for administration of open-label study drug, with 
the option to have infusions administered at the home of the subject after 3 months if they have 
not had a moderate to severe IAR during those 3 months. Changes in the protocol-prescribed 
duration of study drug infusion due to safety or tolerability issues will be documented in the 
eCRF. In addition to the assessments noted in Table 4 (subjects who participated in 
Study ATB200-03), the site should follow their facility guidelines for performing infusions to 
monitor vital signs or other safety procedures that may be in place. 
At each visit through Week 6, additional safety assessments (eg, clinical laboratory tests) will be 
performed for monitoring of initial safety. In addition, subjects will be monitored for 3 hours 
after the end of the first 3 infusions (ie, Day 1 and Weeks 2 and 4) by study personnel who are 
trained in diagnosing and treating acute hypersensitivity reactions and who have immediate 
access to medication and equipment to treat such reactions. Any additional monitoring according 
to standards at individual sites should also be performed. Any signs or symptoms noted during or 

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after the infusion should be reported as an AE. All assessments will be performed before infusion 
of study drug. No efficacy assessments will be performed at these visits. 
If consistent with local laws and regulations, subjects may be considered eligible for 
administration of cipaglucosidase alfa/miglustat at their home. Eligible subjects may request 
participation in the home infusion program with requests granted on a case-by-case basis 
following discussion between the Amicus medical monitor and investigator with prior approvals 
from the relevant IRBs, IECs, or REBs, and regulatory authorities. 
Home infusions of cipaglucosidase alfa will be performed by a certified mobile research nurse 
provided by an Amicus-designated home infusion service provider. Certified mobile research 
nurses will be trained to recognize and manage subjects in the event of an IAR (see 
Section 13.1.3) and will be equipped with emergency medicines and devices to treat subjects 
who have an IAR. Details regarding the infusion (eg, dose, flow rate) and observations will be 
documented by the certified mobile research nurse and promptly communicated to the 
investigator. 
All subjects participating in the home infusion program will be required to complete all 
functional assessments at the protocol-specified site visits. 
Subjects who participate in the home infusion program must meet all of the following inclusion 
criteria and none of the following exclusion criteria. 
Inclusion criteria for home infusion program: 
• Subject resides in a country where it is permissible to administer alglucosidase alfa 
outside of a hospital setting. 
• Home site meets the following requirements regarding feasibility for ERT infusion: 
− Availability of sufficient space to prepare and administer cipaglucosidase alfa 
infusion 
− Availability of utilities and equipment required for storage of study drug upon 
receipt 
− Accessibility for delivery of study drug and associated supplies 
− Accessibility of trained certified mobile research nurse for 
preparation/administration 
− Ability to prepare cipaglucosidase alfa lyophilized drug product for reconstitution 
− Sufficient space to administer cipaglucosidase alfa infusion 
− Ability to properly dispose of waste and discard used medical supplies 
• Amicus/designee deems the home site to be appropriate for home infusion following 
home assessment. 
• Investigator agrees to collaborate with the home infusion agency/certified mobile 
research nurse with respect to providing advice and support as needed by the certified 
mobile research nurse. 

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Exclusion criteria for home infusion program: 
• Subject experiences a moderate or severe IAR, or a mild IAR that is not controlled 
with medication after receiving study drug during this study, or with a history of a 
recurrent severe or life-threatening IAR including anaphylaxis at any time. 
12.2.3. 
Post-baseline Assessment Visits 
Assessments may occur over 2 days for each post-baseline visit, provided all assessments are 
performed before administration of study drug. 
If infusions were missed close to the scheduled assessments, it should be communicated with the 
Amicus Medical Monitor to determine on a case-by-case basis whether catch-up infusions are 
needed and how many catch-up infusions are needed prior to the study assessments. 
12.2.4. 
Unscheduled Visits 
Unscheduled visits may be conducted at any time at the investigator’s discretion for medical 
reasons (eg, evaluation of AEs, local laboratory tests for safety, other safety assessments). 
12.2.5. 
End of Study/Early Termination 
Subjects who complete the study or discontinue study drug for any reason will be asked to return 
for the End of Study/Early Termination Visit. The End of Study visit is performed as the final 
full assessment visit for a subject who has completed the study as defined in Section 8.5. The 
Early Termination visit is performed as the final full assessment visit for a subject who ends 
treatment with the study drugs prior to completing study treatment. 
If infusions were missed close to the scheduled assessments on the last week of the study, it 
should be communicated with Amicus to determine on a case-by-case basis whether catch-up 
infusions are needed and how many catch-up infusions are needed prior to the study assessments. 
12.2.6. 
Follow-up Period 
A 30-day safety follow-up visit for monitoring of any AEs that were ongoing at end of study 
should be conducted. 
12.3. 
Description of Study Assessments 
All assessments will occur according to the Schedule of Assessments displayed in Table 4 for 
subjects who participated in Study ATB200-03. 
For subjects continuing in the study after approval of this amendment, please refer to Appendix 1 
for the updated Schedule of Assessments (Table 10). 
Any study procedures that involve supine positions may be deferred if the subject is unable to 
complete them in a supine position. 
If a subject is ill or injured at a scheduled visit, functional assessments (ie, 6MWT, motor 
function tests, muscle strength tests, and pulmonary function tests) may be deferred to an 
unscheduled visit when the subject’s condition has improved, in consultation with the medical 
monitor. 

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Significant findings for vital signs, physical examinations, clinical laboratory tests, or ECGs that 
were not present prior to start of treatment and meet the definition of an AE must be recorded on 
the AE eCRF page. 
12.3.1. 
Demographic Data Collection 
Demographics (date of birth, sex, and race) will be recorded for any subject who signs informed 
consent to participate in this study. This information is required for interpretation of key efficacy 
(eg, % predicted FVC) and safety (laboratory parameters with age/gender-specific normal 
ranges) outcomes. 
12.3.2. 
Medical History 
For subjects who participated in Study ATB200-03, medical history findings reported for 
Study ATB200-03 will also be recorded for this study. 
12.3.3. 
Prior/Current Medications 
For subjects who participated in Study ATB200-03, any concomitant medications reported 
during Study ATB200-03 that have not been stopped before the Baseline Visit for this study will 
be recorded as prior medications. 
All subjects will be asked to report any medications (including, to the extent possible, dosage, 
frequency, start dates, and stop dates) that they are currently taking. All prescription and 
nonprescription medications will be recorded. In addition, any nondrug therapies (including 
physiotherapy and occupational therapy) that a subject is undergoing are to be recorded. Details 
regarding use of ambulatory aids such as a cane or walker as well as respiratory support such as 
continuous positive airway pressure or bi-level positive airway pressure should also be recorded. 
Medications/procedures will be reviewed at each study visit in order to capture any changes that 
occurred during the study period. 
Concomitant medications and nondrug therapies (eg, procedures, surgery, physical therapy, or 
assistive devices) specifically associated with an AE or IAR should be entered into the 
corresponding eCRFs. 
12.3.4. 
Physical Examination 
Complete physical examinations will include assessment of head, ears, eyes, nose, throat 
(HEENT), respiratory, cardiovascular, lymphatic, gastrointestinal, and neurologic systems. 
Brief examinations will be targeted towards any abnormal findings noted at the previous visit 
and/or review of ongoing AEs. 
All body systems with no abnormal findings must be noted so in the source documents. 
12.3.5. 
Body Weight and Height 
Body weight will be entered into the IRT system for calculation of dose. Calibration or 
standardization of the scale used to measure body weight should be performed on a monthly 
basis or according to scale specifications. 

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For subjects who participated in Study ATB200-03, height will be measured at the Baseline Visit 
only if height is not available in the records for that study. 
12.3.6. 
Vital Signs 
Vital signs include blood pressure (systolic and diastolic), respiration rate, heart rate, and 
temperature. Blood pressure measurements should be obtained using the same arm. 
Measurements will be taken with the subject in sitting position after having rested for a 5-minute 
period. The same position should be used at all visits. 
12.3.7. 
Adverse Events  
Reporting of AEs begins after the first dose of open-label study drug in this study. As required 
by their institutions, investigators will be responsible for reporting AE information to their IRB, 
IEC, or REB (see Section 13). If the start date of an AE is before the first dose of open-label 
study drug, it should be captured as medical history. 
12.3.8. 
Patient-reported Outcomes 
Patient-reported outcomes include the R-PAct Scale, EQ-5D-5L, PROMIS instruments for 
physical function, fatigue, dyspnea, and upper extremity, and SGIC, as available. 
The R-PAct scale is an 18-item questionnaire to measure limitations in activities and restriction 
in social participation. Possible responses to questions are as follows: unable to perform, able to 
perform, but with difficulty, and able to perform without difficulty. A raw score ranging from 
0 to 36 points is generated. 
The EQ-5D-5L comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate 
problems, severe problems, and extreme problems. Subjects are asked to indicate their health 
state by ticking the box next to the most appropriate statement in each of the 5 dimensions. The 
subject’s self-rated health is also recorded on a vertical visual analogue scale, where the 
endpoints are labeled “The best health you can imagine” and “The worst health you can 
imagine.” 
Short forms for the PROMIS instruments for physical function (20 items) and upper extremity 
(7 items) measure signs and symptoms using general questions without a temporal reference. 
Short forms for the PROMIS instruments for fatigue (8 items) and dyspnea severity (10 items) 
measure signs and symptoms over the past 7 days. A 5-point scale is used for each instrument 
(though responses may vary within or among instruments), and a total score is generated for each 
instrument. 
The SGIC is designed to record the subjects’ impression of their functional status since starting 
open-label study drug using a 7-point scale ranging from “very much worse” to “very much 
improved.” The administrator of the SGIC will read the questions to the subject and record the 
answers. 
Subjects are to complete patient-reported outcome questionnaires before any other study 
assessment, if the questionnaires are available in that subject’s language. Separate detailed 
instructions will be provided in the study functional assessment manual. 

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12.3.9. 
Physician’s Global Impression of Change 
The PGIC is designed to record the physician’s assessment of the subject’s status, taking into 
account the subject’s signs and symptoms and other neuromuscular symptoms, and signs relative 
to their status at the Baseline Visit. 
12.3.10. 
Electrocardiogram 
A standard 12-lead ECG will be performed after subjects have rested for approximately 
5 minutes prior to the start of the ECG recording. Subjects will be in the supine position 
throughout the ECG evaluation. A central ECG vendor will be used. 
12.3.11. 
Clinical Laboratory Tests 
12.3.11.1. Chemistry, Hematology, and Urinalysis 
Clinical laboratory tests for safety monitoring include serum chemistry (Table 6), hematology 
(Table 7), and urinalysis (Table 8). Clinical laboratory tests will be performed prior to 
administration of study drug. The collection, processing, and shipment of all biological samples 
will be fully described in the study laboratory manual. 
The investigator (or his/her designee) will review each laboratory report from the central 
laboratory and assess any out-of-range laboratory results as “not clinically significant” or 
“clinically significant” (see Appendix 3). Any results that are considered clinically significant 
should 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 or until an etiology is determined. The investigator (or his/her designee) will sign and 
date all laboratory reports. Results for CK, alanine aminotransferase (ALT), and aspartate 
aminotransferase (AST) will be blinded to investigators and reviewed by an unblinded medical 
monitor until treatment assignments in Study ATB200-03 are unblinded to maintain consistency. 
After approval of this amendment, clinical laboratory tests will be performed locally at site. 
Table 6: 
Serum Chemistry Parameters 
ALT 
Creatinine 
Alkaline phosphatase 
GGT 
AST 
Glucose 
Albumin 
LDH 
Bilirubin, total  
Magnesium 
BUN 
Phosphorous 
Calcium, total 
Potassium 
Carbon dioxide, total (bicarbonate) 
Protein, total 
Chloride 
Sodium 
CK 
Uric acid 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
CK = creatine kinase; GGT = gamma-glutamyltransferase; LDH = lactate dehydrogenase 

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Table 7: 
Hematology Parameters 
Platelet count 
Automated white blood cell differential: 
Red blood cell count 
Neutrophils 
White blood cell count (absolute) 
Lymphocytes 
Hematocrit 
Monocytes 
Hemoglobin 
Eosinophils 
Basophils 
Table 8: 
Urinalysis Parameters 
Color 
Ketones 
Appearance 
Blood 
Specific gravity 
White blood cells 
pH 
Nitrite 
Protein 
Bilirubin 
Glucose 
Microscopy of sediment 
12.3.11.2. Pregnancy Tests 
All female subjects of childbearing potential will have a urine pregnancy test performed at 
infusion visits. If the urine pregnancy test has a positive result, study drug will not be 
administered and a confirmatory serum pregnancy test will be performed. Any pregnancy that 
occurs during the study period must be reported, and that subject must be withdrawn from the 
study (see Section 13.4). 
12.3.12. 
Immunogenicity Assessments 
Blood samples for measurement of anti-rhGAA antibodies (total and neutralizing) will be 
collected predose along with the clinical safety laboratory samples. 
Neutralizing antibody assays may include the following: 
• inhibition of rhGAA-mediated hydrolysis of 4-methylumbelliferyl-glucoside 
• inhibition of rhGAA-mediated hydrolysis of glycogen 
• inhibition of rhGAA binding to cation-independent mannose 6-phosphate receptor 
Subjects who are confirmed to have a positive result for anti-rhGAA antibodies from the 30-day 
safety follow-up visit will continue to have follow-up immunological testing as long as they have 
a positive result for up to 12 months after the last dose of study drug (ie, at 6 months and 
12 months) or until they begin treatment with an investigational therapy or an ERT that is 
approved by the local health authority and is commercially available or they start receiving 
cipaglucosidase alfa/miglustat through a post-trial access program. 
If a subject experiences anaphylaxis or a moderate to severe IAR (in the opinion of the 
investigator) as outlined in Section 13.1.3, 3 blood draws will be required for measurement of 

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immunoglobulin E (IgE) levels. The first blood draw should be obtained 6 to 8 hours after onset 
of the infusion reaction, the second blood draw at 24 hours, and the third immediately before the 
next administration of study drug. Because anti-rhGAA or IgE results could potentially reveal a 
subject’s treatment assigned in Study ATB200-03, these results will not be included on 
laboratory test reports. 
Total GAA protein concentration will also be measured from the same blood sample since assay 
sensitivity for both anti-rhGAA antibodies and IgE can be affected by GAA protein levels. 
An unblinded medical monitor not involved in the operational aspects of the study will manage 
review of all immunogenicity results, until Study ATB200-03 is unblinded. 
12.3.13. 
Sample Collection for Pharmacokinetic Assessments (Sites in Japan Only) 
Japanese subjects who participated in Study ATB200-03 will have sparse blood samples 
collected just prior to initiation of cipaglucosidase alfa infusion (time 0) and at 1, 4, 6, 12, and 
24 hours after the start of cipaglucosidase alfa infusion at either Week 2, 4, or 6, and at Week 52 
(Table 5) for plasma total GAA protein signature peptide T09 and plasma miglustat. Collection 
of the 12-hour sample will be optional. 
Vital signs may be measured after each PK blood sample for monitoring of safety, as per local 
clinical guidelines, but results will not be recorded in the eCRF. 
Pharmacokinetic assessment in Japanese subjects is necessary to fulfill local regulatory 
requirements for marketing applications. 
12.3.14. 
Creatine Kinase and Urinary Hexose Tetrasaccharide  
Creatine kinase is a type of enzyme found within muscles. Injury to the membrane surrounding 
muscle cells allows CK to leak into the bloodstream; therefore, increased levels of CK can be 
indicative of muscle injury. Creatine kinase levels will be measured as part of the serum 
chemistry panel and results will be blinded until treatment assignments in Study ATB200-03 are 
unblinded. 
Levels of urinary Hex4, a biomarker of disease substrate, will be measured. The assay 
specifically targets one hexose tetrasaccharide, the glucose tetrasaccharide Glc4, which is a 
biomarker of glycogen storage. Glc4 is separated from other hexose tetrasaccharides in urine by 
ultra performance liquid chromatography and quantified by stable isotope dilution. The reported 
Hex4 value is actually a measure of Glc4. Concentrations of Glc4 are compared with 
age-matched control ranges. 
12.3.15. 
Biological Specimens 
Any biological specimens remaining at the end of the study may be used for future exploratory 
assays to improve the understanding of Pompe disease and its management. The retention of 
samples is optional; subjects will have the option to agree or refuse to have their samples 
retained. The retained samples will not be used for any future genetic testing. 
These activities are in line with the EU General Data Protection Regulation (GDPR) and any 
other local applicable regulations. 

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12.3.16. 
Pulmonary Function Tests 
Pulmonary function tests to be performed include FVC (sitting and supine), SVC (sitting and 
supine), MIP, MEP, and SNIP. These tests should be performed in the same position and in the 
same order at each study visit. If possible, the tests should be administered by the same person at 
each visit. The identity and qualification of the test administrator will be recorded. Training will 
be provided for site personnel. 
Pulmonary function tests must be performed as detailed in a separate manual. A central vendor 
for pulmonary function tests will be used for this study. 
12.3.17. 
Motor Function Tests  
Motor function tests to be performed include the GSGC test and the TUG test. 
The GSGC consists of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers’ 
maneuver, and arising from a chair. Results of the GSGC include the time required to complete 
the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair 
climb, and Gowers’ maneuver and 1 to 6 points for arising from a chair), and a total score. The 
total score ranges from a minimum of 4 points (normal performance) to a maximum of 27 points 
(worst score). 
For the TUG test, the time it takes for the subject to rise from a chair, walk 3 meters, turn around, 
walk back to the chair, and sit down will be recorded. 
These assessments should be performed without an assistive device (eg, cane, walker). If at any 
time during the study, it is unsafe for a subject to perform an assessment without an assistive 
device, that test should not be performed and a comment should be entered on the source 
document indicating why the assessment was not completed. 
The motor function tests will be performed in the same order at each study visit. If possible, the 
tests should be administered by the same person at each visit. The identity and qualification of 
the test administrator will be recorded. Training will be provided for site personnel by a central 
vendor. 
Separate detailed instructions for these tests will be provided in the study functional assessment 
manual. 
12.3.18. 
6-Minute Walk Test 
The 6MWT is an assessment of ambulatory function that involves the skeletal muscle, 
pulmonary, and cardiac systems as well as motor function. 
The objective of the 6MWT is to walk (not run or jog) as far as possible for 6 minutes. The timed 
walk test should be performed with walking shoes on a flat surface. Subjects may use an 
assistive device (eg, cane, walker, rollator) to perform the 6MWT. If they do so at the 
Screening Visit of Study ATB200-03, they should use the same assistive device at all subsequent 
visits. If a subject has a change in the use of an assistive device that was used to perform the 
6MWT during Study ATB200-03, then the 6MWT must be repeated at the Baseline Visit. Also, 
any changes in the use of an assistive device must be clearly documented and include description 
of assistive device and date of change. 

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The tests should be administered by the same person, as much as possible, at each visit. The 
identity and qualification of the test administrator will be recorded. Training will be provided for 
site personnel by a central vendor. 
The clinical evaluator will make an assessment of validity (ie, valid or invalid), according to 
detailed criteria in the study functional assessment manual. The assessment of validity by the 
clinical evaluator will be used for determining eligibility at screening. 
Separate detailed instructions for this test will be provided in the study functional assessment 
manual. 
12.3.19. 
Muscle Strength Testing 
Muscle groups tested include shoulder abductors, shoulder adductors, elbow extensors, elbow 
flexors, hip flexors, hip abductors, hip adductors (hand-held dynamometer only), knee extensors, 
and knee flexors. 
Manual muscle strength will be assessed by neurological (physical exam) assessment using the 
Medical Research Council scale (0 to 5 points, with 5 indicating normal function). The same 
rater and method must be utilized as much as possible throughout the subject’s participation in 
the study. 
Quantitative muscle strength will also be measured using a hand-held dynamometer and 
measured in kg of pressure. If possible, the tests should be administered by the same person at 
each visit. The identity and qualification of the test administrator will be recorded. Training will 
be provided for site personnel. 
Separate detailed instructions for these tests will be provided in the study functional assessment 
manual. 

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13. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
13.1. 
Definitions 
13.1.1. 
Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product, biologic (at any dose), or medical device, which 
does not necessarily have a causal relationship with the treatment. Therefore, an AE can be any 
unfavorable and unintended sign, symptom, or disease temporally associated with the use of a 
medical product, whether or not considered related to the medical product. 
According to this protocol, expected or anticipated evolution of the disease under treatment will 
be evaluated as part of the disease symptom assessment. Changes in Pompe disease symptoms 
must be reviewed by the investigator or a medically qualified sub-investigator and recorded as 
“clinically significant” or “not clinically significant” in subjects’ source records (see 
Appendix 3). Expected or anticipated changes in the clinical condition may not qualify as AEs. 
However, if there is a clinically relevant worsening of a sign or symptom of the disease under 
treatment and the outcome fulfills the definition of an AE, it must be reported as directed in the 
protocol. 
For subjects who participated in Study ATB200-03, any AE that begins after the first dose of 
open-label study drug will be considered a treatment-emergent adverse event (TEAE). 
Subjects experiencing AEs should be followed up until their health has returned to baseline 
status or stabilized. 
Adverse events 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 the last 
visit in Study ATB200-03 and/or, in the investigator’s opinion, represent a clinically 
significant change in the subject’s health during study participation 
13.1.2. 
Serious Adverse Events 
A SAE is any AE that 
• results in death 
• is life-threatening 
− An AE, in the view of either the investigator or Amicus, that 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. 

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• requires inpatient hospitalization or prolongs existing hospitalization 
− Hospitalization signifies that 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 preplanned treatment of a pre-existing condition 
do not have to be reported as SAEs, provided that 
− the condition is documented in the subject’s medical history and has not 
worsened since the informed consent form (ICF) was first signed, and 
− the planned procedure is documented in the subject’s eCRF at the Baseline 
Visit. 
Note: Outpatient procedures performed in a hospital do not qualify as an SAE. 
− 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. 
− Hospitalizations solely based on logistics (eg, subject is admitted due to limited 
hospital accessibility for what would otherwise be an outpatient procedure) do not 
have to be reported as SAEs. 
− These hospitalizations should be clearly defined as such in the subject’s 
source record. 
• results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, as decided by the investigator 
• is a congenital anomaly/birth defect 
An important medical event that may not result in one of the above-mentioned serious outcomes 
may be considered an SAE when, based on appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the 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. 
For all subjects, AEs and SAEs will be reported from time of first dose of open-label study drug 
until 30 days after the last dose of study drug. If the investigator becomes aware of an SAE in a 
subject or receives an unsolicited report of an SAE from a subject more than 30 days after the 
last treatment, and considers the event possibly, probably, or definitely related to previous study 
treatment, he or she should contact the Amicus medical monitor to determine how the SAE 
should be documented and reported. 

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13.1.3. 
Infusion-associated Reactions 
An IAR is defined as a disorder characterized by 1 or more adverse reaction(s) to the infusion of 
pharmacological or biological substances. These reactions are classified into 2 major subtypes, 
early and late, according to the time interval between the infusion and the onset of an 
infusion-related AE. 
The reactions are divided into 5 severity grades as follows: 
1. Mild (requires observation only); for example, transient flushing or rash
2. Moderate (minimal, usually oral, intervention suffices); for example,
urticaria/myalgia/drug fever
3. Severe (vital organ involved yet not in a life-threatening manner; usually requires
parenteral medication); for example, bronchospasm/angioedema/hypotension
4. Life threatening (multisystem involvement of vital organs, urgent and critical care
required); for example, systemic anaphylactic reaction
5. Death
Early IARs is any symptom or sign occurring during or within 24 hours of completion of the 
infusion and deemed a drug-related AE by the investigator, unless an alternative obvious 
explanation exists, eg, mechanical fall. Early IARs commonly involve 1 or more of the following 
systems: skin (urticaria and erythema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), 
bronchopulmonary tissues (wheezing, bronchospasm), and gastrointestinal tract (diarrhea, 
vomiting). 
Late IAR is any symptom or sign occurring more than 24 hours (usually 1 to 3 days) after 
completion of the infusion that, in the investigator’s opinion, fits the clinical description of a 
symptom or sign associated with an IAR. The most common symptoms of late IARs are pruritic 
skin eruptions, fever, malaise, and polyarthralgia. 
Note: The list of IAR symptoms provided in Table 9 is not comprehensive. It is meant to serve as 
a guideline to the investigators to report and manage IAR as AE. Table 9 also provides a 
guideline for management of IARs and anaphylaxis (see also Appendix 2). The guideline is 
intended for sites that do not have such procedures in place. It is at the investigator’s discretion 
to follow the guidelines or implement treatment protocol that their center is accustomed to 
following. 
When an IAR occurs, it is important to report and indicate in the eCRF all AEs that are 
associated with the IAR. All available details of the events observed with an IAR are necessary 
to assess the evolution of the AEs after premedication for subsequent infusions. 
In the event that a subject experiences an IAR, the subject should be premedicated for 
subsequent infusions with antihistamines, steroids, and/or acetaminophen, infusion rate 
adjustments, or other steps taken. If these measures are not successful, the investigator/designee 
should contact the medical monitor for guidance. The premedications should be continued for all 
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Table 9: 
Guidelines for Management of Early Infusion-associated Reactions 
Severity 
Symptoms (such as, 
but not restricted to) 
Management Guidelines 
Mild reaction 
Flushing 
Nausea 
Mild headache 
Tachycardia (pulse 
< 100 bpm) 
Abdominal pain 
REDUCE INFUSION RATE BY 50% 
Contact investigator. 
Give oral antihistamine/acetaminophen and/or IV 
antihistamine. 
Prepare emergency equipment for any subsequent study 
drug escalation. 
Subject must be observed at site or medical facility for 2 to 
4 hours after resolution of the symptoms. 
Record all details of times, concomitant medications and 
nondrug therapies, and infusion rates. 
Record all details. Report AE, if applicable. 
IF SYMPTOMS PERSIST: 
STOP THE INFUSION 
After 30 minutes, if subject has improved, increase to 
previous infusion rate on direction of investigator/designee. 
If subject has not improved after 60 minutes, consult with 
investigator as to whether additional medications should be 
administered. 
If subject reacts for second time after return to the prior 
infusion rate, reduce rate by 50% and contact 
investigator/designee. 
IF IN DOUBT, STOP INFUSION 
Moderate 
reaction 
Localized itchiness, 
and/or raised 
Urticarial rash (hives) 
Severe headache 
Fever or shivering 
Tachycardia (pulse 
> 100 bpm) 
Tachypnea 
Flushing 
Nausea 
Irritability 
Headache 
Vomiting 
Diarrhea 
Abdominal cramps 
Myalgia 
** STOP INFUSION ** 
Immediately contact investigator. 
Administer high-flow oxygen if respiratory 
symptoms/distress. 
Give IM or IV antihistamines (eg, promethazine 25 to 
50 mg). 
Give IV fluid bolus, if warranted. 
Give IV steroids (hydrocortisone 100 mg) on direction of 
investigator/designee. 
Continue management as directed by the 
investigator/designee. 
If deemed appropriate by investigator/designee, resume 
study drug infusion at reduced rate and prepare emergency 
equipment. 
If deemed appropriate by investigator/designee, infusion can 
be suspended and reinitiated 48 hours later with 
premedications and at the infusion rate that was last 
tolerated. 
Observe subject for a minimum of 6 hours after resolution 
of the event. 
Record all details. Report AE, if applicable. 

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Table 9: 
Guidelines for Management of Early Infusion-associated Reactions 
(Continued) 
Severity 
Symptoms (such as, 
but not restricted to) 
Management Guidelines 
Severe 
reaction, 
anaphylaxis, 
or 
anaphylactoid 
reactions 
Chest pain 
Generalized urticarial/ 
angioedema 
Symptomatic 
hypotension (subject 
feeling faint, paleness) 
Hoarseness of 
voice/laryngeal edema 
Bronchospasm 
** STOP INFUSION ** 
Activate emergency response and immediately contact 
investigator. 
For chest pain and symptomatic hypotension, initiate 
emergency procedures. 
Administer high-flow oxygen or intubate and mechanically 
ventilate as appropriate. 
Give IM adrenaline 300 mcg EpiPen into thigh (avoid 
buttock). If no response, repeat dose in 5 minutes. Prepare 
infusion of adrenaline 3 mg/50 mL NS (60 µg/mL), if 
needed. 
Give IV fluids 10- to 20-mL/kg fluid bolus on direction of 
investigator/designee. 
Give IV antihistamines (promethazine 25 to 50 mg in 
10 mL WFI over 2 to 3 minutes). 
Give IV steroids (hydrocortisone 100- to 500-mg bolus IV 
injection; dilute in 10 mL NS for doses between 100 and 
500 mg) and infuse over 2 minutes. 
Give nebulized beta-2 agonists with high-flow oxygen on 
direction of investigator/designee. 
Administer other treatments and/or transfer patient to 
hospital/ICU as recommended by investigator/designee. 
Observe subject for a minimum of 24 hours after resolution 
of the event. 
If deemed appropriate by investigator/designee, study drug 
infusion can be re-initiated 7 to 14 days with premedications 
and at the 4-hour duration. 
Record all details. Report AE, if applicable. 
Abbreviations: AE = adverse event; GAA = human acid α-glucosidase; ICU = intensive care unit; 
IgE = immunoglobulin E; IM = intramuscular; IV = intravenous; NS = normal saline; WFI = water for injection 
Source: Vogel 2010; Sampson, Muñoz-Furlong et al. 2006 
13.1.4. 
Relationship to Study Drug 
The investigator or a qualified sub-investigator will review each event and assess its relationship 
to ERT based on available information according to the following guidelines: 
• Definite: A reaction that follows a distinct temporal relationship from administration 
of the 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. By definition, IARs (immediate or late type) are considered definite (see 
Section 13.1.3). 

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• Probable: A reaction that follows a reasonable temporal sequence from administration 
of the 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 that subject/subject’s clinical state. 
• Possible: A reaction that follows a reasonable temporal sequence from administration 
of the study drug and 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 the 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 the study drug. 
For the purpose of reporting SAEs to regulatory authorities and IRBs/IECs/REBs, any AE 
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 the study drug). Any AE 
assessed as unlikely or unrelated will be considered “not related” to study drug (ie, not associated 
with the use of study drug). 
13.1.5. 
Assessment of Severity 
The following definitions for rating severity will be used: 
• 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. 
When the determination of AE severity rests on medical judgment, the determination of severity 
must be made with the appropriate involvement of the investigator or a qualified 
sub-investigator. 
13.2. 
Reporting of Adverse Events 
Information regarding AEs is to be obtained by questioning or examining the subject. 
For subjects who participated in Study ATB200-03, AEs will be recorded in the eCRF and 
subject’s source record beginning after the first dose of open-label study drug until 30 days after 
the last treatment visit. 
A single diagnosis should be entered when known. If a clear diagnosis cannot be determined at 
the time of the eCRF and subject’s source record entries, each sign and symptom must be 
recorded individually, until a final diagnosis is established. Pompe-related conditions, signs, 

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symptoms, etc, that are present in the subject’s medical history should only be reported as AEs if 
they worsen (ie, increase in severity) during the subject’s participation in the study. 
For each AE reported, the date and time the event started and ended, action taken, outcome 
(resolved, resolved with sequelae, ongoing, or fatal), and severity must be noted. 
All subjects who have AEs, whether or not considered associated with the use of study drug, 
must be monitored to determine the outcome. The clinical course of the AE will be followed up 
according to accepted standards of medical practice, even after the end of the period of 
observation, until a satisfactory explanation is found or the investigator considers it medically 
justifiable to terminate follow-up. Should the AE result in death, a full pathologist’s report 
should be supplied, if possible. For all AEs that require or result in subject discontinuation from 
the study, relevant clinical assessments and laboratory tests will be repeated as clinically 
appropriate, until final resolution or stabilization of the event(s). 
If the investigator considers it necessary to report a nonserious AE in a study subject more than 
30 days after the last visit, he or she should contact Amicus to determine how the AE should be 
documented and reported. 
13.3. 
Reporting Requirements for Serious Adverse Events 
If an AE is serious (as defined in Section 13.1.2), the investigator must submit an SAE report 
form at the time the SAE is identified. All SAEs must be immediately reported by the 
investigator to Amicus or Amicus’ designee, but no later than 24 hours after any study site 
personnel is aware of the event. Serious adverse event report forms must be faxed to the 
designated safety fax number (+1 866-422-1278) or sent via email to 
safetyreporting@amicusrx.com. All supporting documentation available at the time of reporting, 
with all subject identifiers redacted in accordance with local requirements, must be included in 
the fax along with the SAE report form. 
The initial report must be completed as soon as possible. All known details of the SAE and an 
assessment of the causal relationship between the event and study drug, or study procedure 
should be included in the initial report. All information not available at the time of the initial 
report (eg, event end date, discharge summary, or results of diagnostic procedures/evaluations 
related to the event) must be provided in a follow-up report. Follow-up information must be 
reported using the designated fax number within 24 hours of receipt at study sites. 
Every attempt should be made to describe events in terms of a diagnosis. If a clear diagnosis has 
been made, individual signs and symptoms should not be recorded unless they represent atypical 
or extreme manifestations of the diagnosis, in which case they should be reported as separate 
events. If a clear diagnosis cannot be established, each sign and symptom must be recorded 
individually. 
Study endpoints that meet SAE criteria (as per Section 13.1.2) must also be immediately reported 
by the investigator to Amicus or Amicus’ representative but no later than 24 hours after any 
study site personnel is aware of the event. 
If a nonserious event becomes serious, the event must be reported as described above. 

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If the investigator becomes aware of an SAE in a subject or receives an unsolicited report of an 
SAE from a subject more than 30 days after the last treatment, and considers the event possibly, 
probably, or definitely related to previous study treatment, he or she should contact the Amicus 
medical monitor to determine how the SAE should be documented and reported. 
The Amicus Safety Physician will determine the expectedness of AEs according to current safety 
reference document (eg, current Investigator’s Brochure or other safety-related information as 
available). 
13.3.1. 
Additional Reporting Requirements for Suspected Unexpected Serious Adverse 
Reaction 
Any AE that is serious, unexpected, and associated with the use of the study drug (suspected 
unexpected serious adverse reaction [SUSAR], also referred to as Expedited Safety Report and 
Investigational New Drug Safety Report) has additional reporting requirements. All investigators 
conducting clinical studies with the study drug will be notified of such events and must inform 
their IRBs/IECs/REBs as required in accordance with local law. Amicus will ensure that 
SUSARs are reported to regulatory agencies in accordance with local law in each country where 
study sites are located. 
• If the SUSAR is fatal or life-threatening, associated with the use of the study drug, 
and unexpected, regulatory authorities and IRBs/IECs/REBs will be notified within 
7 calendar days after Amicus learns of the event. 
• If the SUSAR is not fatal or life-threatening but is otherwise serious, associated with 
the use of the study drug, and unexpected, regulatory authorities and 
IRBs/IECs/REBs will be notified within 15 calendar days after Amicus learns of the 
event. 
Safety updates will be provided periodically to the regulatory authorities and IRBs/IECs/REBs 
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. 
13.3.2. 
Overdose/Underdose 
A product overdose/underdose (whether accidental or intentional) is considered by Amicus to be 
an AE and must be recorded as such in EDC. If a subject experiences an overdose or an 
underdose during the course of the study (as defined below for each product, whether 
symptomatic or not), the Amicus medical monitor must be notified within 5 working days of the 
investigator or study personnel first becoming aware of the overdose/underdose. 
• Overdose 
− cipaglucosidase alfa: ≥ 20% higher than the assigned dose of study drug for a 
single administration (20 mg/kg x patient weight) 
− miglustat: ≥ 1 capsule more than the assigned dose of study drug for a single 
administration 

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• Underdose 
− cipaglucosidase alfa: ≥ 20% lower than the assigned dose of study drug for a 
single administration (20 mg/kg x patient weight) 
− miglustat: ≥ 1 capsule less than the assigned dose of study drug for a single 
administration (eg, if a subject is supposed to receive 4 capsules, but only receives 
1, 2, or 3 capsules; or if a subject is supposed to receive 3 capsules but only 
receives 1 or 2 capsules) 
Follow-up information must be forwarded on the outcome of the overdose/underdose as 
applicable. If an SAE occurs in conjunction with the overdose/underdose, the same SAE 
reporting requirements described in Section 13.3 apply. 
13.3.3. 
Missed Dose 
If a subject is unable to schedule a treatment (infusion) up to 7 days after the scheduled date, this 
is considered as a missed dose. The subject will receive his or her next dose per his or her 
schedule, ie, approximately 4 weeks following the previous dose, since the subject missed a dose 
at 2 weeks following the last dose. This is recorded as a protocol deviation. Any AE that occurs 
as a result of missed dose should be recorded as such. The Amicus medical monitor should be 
notified as soon as feasible after the investigator or study personnel first become aware of the 
missed dose. Follow-up information on the outcome must be forwarded as applicable. If an SAE 
occurs in conjunction with the missed dose, the same SAE reporting requirements described in 
Section 13.3 apply. 
Study subjects who missed infusions close to their scheduled assessments at Week 12, Week 26, 
or at any of the study visits scheduled every 26 weeks after Week 26 should postpone the 
assessments and receive a sufficient number of catch-up infusions prior to undergoing the study 
assessments. Each instance of missed infusion should be discussed with, and course of action 
approved by, the medical monitor. A reason for the missed visit should be entered into the EDC. 
The relevant IRBs, IECs, and REBs should be notified of any deviations from the protocol. 
13.4. 
Reporting of 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 this study, or if the female partner of a 
male subject becomes pregnant during the subject’s participation in the study, the event must be 
reported within 5 working days of the investigator or study personnel becoming aware of the 
pregnancy. Study drug will be discontinued, and the subject will be monitored for the duration of 
pregnancy and the baby for 6 months following birth. If an SAE occurs in conjunction with the 
pregnancy, the SAE must be reported as described in Section 13.3. Amicus will provide 
pregnancy report forms and instructions to study personnel regarding collection of pregnancy 
and outcome information (subject to receipt of data privacy release approvals where required 
under local privacy laws). 

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The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the subject was withdrawn 
from the study. 
All reports of congenital abnormalities/birth defects are SAEs. Spontaneous miscarriages should 
also be reported and handled as SAEs. Elective abortions without complications should not be 
handled as AEs. 

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14. 
DATA MANAGEMENT 
For this study, subject data will be entered into an electronic data capture system managed by 
Amicus (or designee). The data will be transmitted via a secure electronic method to Amicus (or 
designee) as defined in the Data Management Plan. 
Management of clinical data will be performed in accordance with applicable Amicus standards, 
ICH, GCP, CFR Part 11, and data cleaning procedures to ensure the integrity of the data 
(eg, determining errors and inconsistencies in the data and ensuring data are corrected by site 
personnel or designees). 
After database lock, each study site will receive an electronic file containing all of their 
site-specific eCRF data as entered into the electronic data capture system for the study, including 
full discrepancy and audit history. Additionally, an electronic copy of all of the study site’s data 
from the study will be retained by Amicus and designee for storage. In the event that the subject 
revokes authorization to collect or use protected health information, the investigator retains the 
ability to use all information collected prior to the revocation of subject authorization. 

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15. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
The final analysis of the whole data set detailed in this section will be performed for the final 
CSR based on a data cutoff date of 31 December 2024. Any data collected after this date will be 
provided as an addendum to the final CSR when all subjects have completed the study or have 
been withdrawn from the study. 
For subjects continuing in the study after approval of this amendment, please refer to Appendix 1 
for details on the data analysis and statistical considerations. 
15.1. 
Endpoints 
15.1.1. 
Safety Endpoints 
The long-term safety profile of cipaglucosidase alfa/miglustat will be characterized using 
incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug, frequency and 
severity of immediate and late IARs, and any abnormalities noted in other safety assessments 
(eg, clinical laboratory tests, ECGs, vital signs). Immunogenicity to cipaglucosidase alfa will 
also be described. 
15.1.2. 
Efficacy Endpoints 
Efficacy endpoints are as follows: 
• change from baseline in 6MWD 
• change from baseline in 6MWD (% predicted) 
• change from baseline in sitting FVC (% predicted) 
• change from baseline in the manual muscle test score for the lower extremities 
• change from baseline in the total score for the PROMIS – physical function 
• change from baseline in the total score for the PROMIS – fatigue 
• change from baseline in the following variables related to motor function: 
− GSGC total score 
− time to complete the 10-meter walk (ie, assessment of gait) of the GSGC test 
− time to complete the 4-stair climb of the GSGC test 
− time to complete the Gowers’ maneuver of the GSGC test 
− time to arise from a chair as part of the GSGC test 
− change from baseline in the time to complete the TUG test 
• change from baseline in the following variables related to muscle strength: 
− manual muscle test score for the upper extremities 
− manual muscle test total score (upper and lower extremities combined) 
− quantitative muscle test value (kg) for the upper extremities 

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− quantitative muscle test value (kg) for the lower extremities 
− quantitative muscle test total value (kg) (upper and lower extremities combined) 
• change from baseline in the following variables from patient-reported outcome 
measures: 
− total score for the PROMIS – dyspnea 
− total score for the PROMIS – upper extremity 
− R-PAct Scale total score 
− EQ-5D-5L health status 
• actual value of the subject’s functional status (improving, stable, or declining) 
pertaining to the effects of study drug in the following areas of life, as measured by 
the SGIC: 
− overall physical well-being 
− effort of breathing  
− muscle strength 
− muscle function 
− ability to move around 
− activities of daily living 
− energy level 
− level of muscular pain 
• actual value of the subject’s functional status (improving, stable, or declining), as 
measured by the PGIC 
• change from baseline in the following measures of pulmonary function, as follows: 
− sitting SVC (% predicted) 
− MIP (cmH2O)  
− MIP (% predicted) 
− MEP (cmH2O) 
− MEP (% predicted) 
− SNIP (cmH2O) 
15.1.3. 
Pharmacodynamic Endpoints 
Pharmacodynamic endpoints are as follows: 
• change from baseline in serum CK level 
• change from baseline in urinary Hex4 level 

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15.1.4. 
Pharmacokinetic Endpoints (in Subjects at Sites in Japan Only) 
Pharmacokinetic endpoints (applicable for subjects at sites in Japan only): 
• sparse blood sampling for determination of total GAA protein levels and miglustat 
concentrations in plasma for a population PK analysis 
Pharmacokinetic endpoints derived from a population PK analysis of total GAA protein and 
miglustat concentrations will be provided in a separate modeling and simulation plan. 
15.2. 
Sample Size Considerations 
No formal sample size calculation was performed for this open-label extension study. The 
maximum sample size for this study is based on the number of subjects who complete 
Study ATB200-03, which has a target enrollment of 110 subjects. 
15.3. 
Data Analysis Considerations 
The Statistical Analysis System (SAS®) version 9.4 (or latest version at the time of the analysis) 
and R© software will be used for all statistical procedures and analyses. 
Full details of the data and analysis methods will be provided in the statistical analysis plan. 
15.3.1. 
Analysis Populations 
The open-label extension enrolled subjects (OLE-ES) is a subset of the ATB200-03 
intent-to-treat (ITT) population, and it includes all subjects who satisfied the eligibility 
requirements (based on the inclusion and exclusion criteria) and entered Study ATB200-07. This 
population will be used for the analyses of all efficacy and pharmacodynamic endpoints 
involving Studies ATB200-03 and ATB200-07 integrated data. 
The open-label extension full analysis set (OLE-FAS) includes all subjects who entered the OLE 
Study ATB200-07 who had both a valid baseline and at least one post-baseline assessment, for at 
least 1 of these efficacy endpoints (6MWD, sitting % predicted FVC, MMT-lower extremities, 
PROMIS – physical function, PROMIS – fatigue, and GSGC). This analysis set will be used for 
the analyses of the main efficacy and pharmacodynamic endpoints involving Study ATB200-07 
stand-alone data. 
The open-label extension safety population includes all subjects who took at least 1 dose of 
cipaglucosidase alfa/miglustat co-administration in Study ATB200-07. This population will be 
used for the summaries of medical history, drug exposure, and any other specific safety-related 
summaries for Study ATB200-07 stand-alone data. 
The safety population consists of all subjects who took at least 1 dose of study drug in either 
Study ATB200-03 or Study ATB200-07. This population will be analyzed per the actual 
treatment received and will be used for all integrated safety summaries. 
The treatment switched population is defined as subjects who were randomized to and received 
alglucosidase alfa/placebo in Study ATB200-03 and subsequently received cipaglucosidase 
alfa/miglustat in Study ATB200-07. This population will be used for specific analyses involving 
these treatment-switched subjects. 

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15.3.2. 
Treatment Groups 
Appropriate reporting treatment groups will be defined in the statistical analysis plan for all 
analyses involving ATB200-07 stand-alone data as well as ATB200-03 and ATB200-07 
integrated data. 
15.3.3. 
Statistical Methods 
15.3.3.1. Interim Analyses 
Interim analysis or analyses may be performed for purposes of writing an interim clinical study 
report. 
15.3.3.2. Adjustment for Multiple Comparisons/Multiplicity 
No adjustment for multiplicity will be performed. All analyses will be descriptive. 
15.3.3.3. Missing Data Handling 
For all efficacy endpoints based on patient-reported outcome/clinical outcome assessment 
instruments, the scoring algorithms (including the standard or published data imputation or 
pro-rating methods contained in the scoring algorithms) will be implemented. 
No data imputation are planned for missing efficacy data. If any imputations are decided upon 
later, the details will be provided in the statistical analysis plan. 
In general, missing safety data will not be imputed. However, attributes such as missing dates for 
AEs and concomitant medications will be imputed using similar methods as described for 
ATB200-03 in order to ensure consistency. Details will be provided in the statistical analysis 
plan. 
15.3.3.4. Windowing Conventions 
By-visit assessments for safety and efficacy will be summarized based on visit windows. 
15.3.3.5. Statistical Tests 
No formal hypotheses are planned to be tested. Unless otherwise specified, only descriptive 
statistics will be presented. Any inferential analyses will be presented for summary purposes. 
Where appropriate, 2-sided 95% confidence intervals will also be provided for summary 
purposes. 
15.3.3.6. Common Calculations 
In general, continuous variables will be summarized using descriptive statistics (the number of 
subjects with available data, mean, standard deviation, median, minimum, and maximum). 
Categorical variables will be summarized using counts and percentages. 

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15.3.4. 
Analyses 
15.3.4.1. Efficacy Analyses 
In general, continuous data will be summarized using descriptive statistics, and categorical data 
will be summarized using counts and percentages, as described above in Section 15.3.3.6. 
Specific analysis details and display format will be described in the statistical analysis plan. 
15.3.4.1.1. Analyses of Ambulatory Function, Motor Function, Pulmonary Function, and 
Muscle Strength 
The OLE-FAS and OLE-ES populations will be used for the analysis of 6MWD, FVC 
% predicted, GSGC total score, other manual muscle tests, quantitative muscle tests, and other 
pulmonary function tests. The % predicted 6MWD will also be summarized, where the predicted 
value will be calculated using the reference equations from Enright and Sherill (Enright and 
Sherill 1998). These continuous endpoints will be summarized as described in Section 15.3.3.6, 
by treatment group and visit. The change from baseline will be similarly summarized by 
treatment group and visit, and the 95% confidence intervals for the mean change will be 
provided for each treatment group. In addition, these analyses will be conducted on the treatment 
switched population (where applicable) for 6MWD and FVC % predicted. 
15.3.4.1.2. Patient-reported Outcomes and Physician’s Global Impression of Change 
The OLE-FAS and OLE-ES populations will be used for patient-reported outcome analyses. 
Summary of each item as well as total score (raw total score and change from baseline in total 
score) for R-PAct Scale, EQ-5D-5L (domain scores are to be analyzed as both categorical and 
continuous variables), and PROMIS instruments will be summarized by treatment group and 
visit. The change from baseline in the total scores will be analyzed as described in 
Section 15.3.3.6, by treatment group and visit, and the 95% confidence intervals for the mean 
change will be provided for each treatment group. 
Each item/domain of the SGIC will be summarized by treatment group and visit. The scores will 
be analyzed as both categorical and continuous variables. Additionally, the response scale for 
each item will be divided into 3 categories (improving, stable, or declining) which reflect the 
functional status, and these will be summarized by treatment group. 
Summary of response score for actual values for PGIC will be summarized by treatment group 
and visit. 
15.3.4.2. Biomarker Analyses 
The OLE-ES population will be used for biomarker analyses involving serum CK and urinary 
Hex4. These continuous endpoints will be summarized as described in Section 15.3.3.6, by 
treatment group and visit. Changes from baseline will be similarly summarized by treatment 
group and visit, and the 95% confidence intervals for the mean and/or median change will be 
provided for each treatment group. 
15.3.4.3. Pharmacokinetic Analyses (Data from Sites in Japan Only) 
After sparse sampling in Japanese subjects, PK endpoints derived from a population PK analysis 
of total GAA protein and miglustat concentrations will be provided in a separate modeling and 

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simulation plan. These data will be incorporated into previously developed population PK 
models and will be used to update the analyses. 
The effects of demographic factors on variability of cipaglucosidase alfa and miglustat PK in 
Japanese subjects will be investigated throughout the modeling process. 
15.3.4.4. Safety Analyses 
Safety analyses will be based on the safety population (for ATB200-03 and ATB200-07 
integrated data) as well as the open-label extension safety population (for ATB200-07 
stand-alone data). 
Safety data will be summarized using descriptive statistics for continuous data and using counts 
and percentages for categorical data, as described in Section 15.3.3.6. 
Exposure to study medication will be calculated in weeks and analyzed as continuous variables 
using descriptive statistics. In addition, the duration of exposure will be categorized and a 
frequency distribution of the categories (each summarized by count and percentage) will be 
presented. 
An overall summary of incidence of AEs (which includes the total number of TEAEs, total 
number of serious TEAEs as well as the total number of subjects) will be presented. The number 
and percentage of subjects who experienced nonserious TEAEs as well as serious TEAEs will be 
summarized by preferred term within system organ class. The summary of nonserious and 
serious TEAEs will also be presented by intensity (mild, moderate, severe), as well as by 
relationship to study medication. In addition, the number of AEs (as opposed to the number and 
percentage of subjects) will be presented. 
Serious adverse events, including deaths, will be summarized and listed. Separate listings of 
death, SAEs (treatment-emergent and nontreatment-emergent), and discontinuations due to AEs 
will be provided. 
Summaries and listings will also be provided for deaths, SAEs, and AEs leading to 
discontinuation and infusion-associated reactions. Adverse events will be coded using Medical 
Dictionary for Regulatory Activities version 18 or higher. 
Clinical laboratory results, ECG parameters, and vital signs will be summarized using descriptive 
statistics (number, mean, median, standard deviation, minimum, and maximum) by treatment 
group and visit for actual values and changes from baseline. The proportion of subjects with 
abnormalities will be provided for clinical laboratory results, ECGs, and vital signs. Shift tables 
will also be provided for clinical laboratory results. 
Prior and concomitant medications and nondrug therapies will be summarized by treatment 
group. Concomitant medications terms will be coded using the World Health Organization Drug 
Dictionary (September 2013 DDE). 
15.3.4.5. Immunogenicity Analyses 
The effect of immunogenicity results on efficacy and safety will be explored. Analysis of 
immunogenicity data will be described separately. 

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16. 
STUDY CONDUCT CONSIDERATIONS 
This global study will include both US sites operating under the Investigational New Drug (IND) 
application (ie, IND sites) and foreign sites (ie, non-IND sites). All investigators will be required 
to certify their compliance with both International Council for Harmonisation (ICH) E6 Good 
Clinical Practice (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 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. 
The study will be conducted in compliance with the protocol, with the Regulation (EU) 
No 536/2014, and with the principles of GCP. 
16.1. 
Posting of Information on Publicly Available Clinical Trial Registers 
Amicus will be responsible for registering this clinical study in global public registries that meet 
the requirements specified by the International Council of Medical Journal Editors, such as 
ClinicalTrials.gov, and for publication of study results. Investigators will provide contact 
information to Amicus for the study listing. 
16.2. 
Regulatory and Ethical Considerations 
16.2.1. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
current version of the Declaration of Helsinki and are consistent with ICH/GCP, applicable 
regulatory requirements, and Amicus’ policy on bioethics. 
16.2.2. 
Independent Ethics Committees/Institutional Review Boards Approval and 
Study Compliance 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/IEC/REB, as appropriate. The investigator must submit 
written approval to Amicus (or designee) before he or she can recruit any subject into the study. 
The principal investigator is responsible for informing the IRB/IEC/REB of any amendment to 
the protocol in accordance with local requirements. In addition, the IRB/IEC/REB must approve 
all advertising used to recruit subjects for the study. The protocol must be re-approved by the 
IRB/IEC/REB upon receipt of amendments and annually, if applicable, as local regulations 
require. 
16.2.3. 
Ongoing Information for Independent Ethics Committees/Institutional Review 
Boards 
The information listed below must be submitted to the IECs/IRBs/REBs according to timelines 
specified by individual IEC/IRB/REB-documented submission policies and procedures, or by 
local law: 
• adverse event information 

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• expedited safety reports 
• periodic reports on the progress of the study 
Submissions may be made by Amicus (or designee) or by the investigator. 
16.2.4. 
Subject Information and Informed Consent 
Signed written informed consent is to be obtained from each subject prior to any study-related 
procedures being performed. Consent must be in a language understandable to the subject and 
must specify who informed the subject. Informed consent process must follow local regulations. 
Where required by local law, the person who informs the subject must be a physician. 
The subject must be given the opportunity to read the ICF and have all their questions and 
concerns addressed before giving consent in writing. If the subject is unable to read, oral 
presentation and explanation of the written ICF and information to be supplied to the subject 
must take place in the presence of an impartial witness. Consent must be confirmed at the time of 
consent orally and by the personally dated signature of the subject (eg, subject’s thumbprint or 
mark). Details about why oral presentation was used, how the information was presented, and 
how the subject provided consent must be described in the medical records. In addition, subjects 
are not allowed to share, discuss, or comment on social media about their participation in this 
study. 
A copy of the signed ICF 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 was obtained prior to any study-related procedures and that the subject received a copy 
of the signed ICF. 
The witness and the person conducting the informed consent discussions must also sign and 
personally date the ICF. Until a signed written consent has been obtained, the investigator will 
not undertake any measures specifically required for this study. 
If informed consent is obtained by telephone (as allowed by individual IRBs/IECs/REBs), the 
subject must be provided a copy of the informed consent document in advance of a telephone 
discussion with the investigator. The investigator must explain the research and assess subject 
comprehension of the study according to site consent procedures. If the subject agrees to 
participate, the subject signs the consent form and returns it to the investigator (eg, via fax) for 
signature before any study assessments begin. When the subject is seen at the site, an updated 
in-person consent form will be obtained before any additional study procedures are performed. 
16.3. 
Quality Control (Study Monitoring) 
In accordance with applicable regulations, GCP, and Amicus procedures, Amicus monitors or 
designee will contact the site prior to the start of the study to review with the site personnel the 
protocol; study requirements; and their responsibilities to satisfy regulatory, ethical, and Amicus’ 
or its designee’s requirements. When reviewing data collection procedures, the discussion will 
include identification, agreement, and documentation of data items for which the eCRF will 
serve as the source document. 

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Risk-based monitoring will be performed on the primary characteristics of the study, as detailed 
in the Monitoring Plan. Amicus or its designee will monitor the study as indicated 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) agree to allow the 
monitor direct access to all relevant documents. 
16.3.1. 
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 
agencies 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 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 personnel to discuss the conduct of the study and any 
findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
16.3.2. 
Confidentiality 
Subject names will not be supplied to Amicus. A unique subject number will be recorded in the 
eCRF, and if the subject’s name appears on any other document (eg, a 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 EU GDPR 2016/679). The subject will be 
informed that representatives of Amicus, the IEC/IRB/REB, 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. 
16.3.3. 
Data Protection 
The conduct of this study and the processing of any personal data collected from each subject (or 
from a subject’s healthcare professional or other relevant third-party sources) by the sponsor or 
its designee, the site and the investigator for use in the study will fully adhere to the requirements 
set out in applicable data protection and medical privacy laws or regulations, including, without 
limitation, the GDPR EU 2016/679. The sponsor or its designee shall ensure that at all times it 
has an appropriate legal basis for processing personal data under applicable data protection law. 
Site-based organizational and technical arrangements to avoid unauthorized access vary by site 
but all include access-controlled/access-limited document control and technical solutions 

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including passwords and security control measures to protect study-specific data, both in paper 
and electronic format. 
The investigator shall report any data breaches that might occur to the sponsor or its designee, 
without undue delay. The sponsor has implemented a Business Practice to address Data Breaches 
that complies with the requirements of applicable laws and regulations including the GDPR. The 
Data Breach procedures in the Business Practice provide specific responses to actual or potential 
threats and involve investigation, containment, and mitigation. If applicable, the authorities and 
the data subjects shall be notified of a data breach within the required timeframes of the 
applicable laws and regulations, including those of the GDPR. 
16.3.4. 
Protocol Amendments and Deviations 
If a clarification on a procedure or an error is found in the protocol, a protocol clarification 
memo will be sent to all sites and the IRB/IEC/REB before an amendment is issued. 
Changes to the administrative aspects of the study (eg, changes in contact information or study 
personnel) will not require formal protocol amendments or IRB/IEC/REB approval but can be 
treated as administrative amendments. However, the IRB/IEC/REB should be kept informed of 
such changes. 
Nonadministrative changes to the protocol, initiated either by Amicus or the investigator, will 
require a formal amendment procedure. Approval of all amendments must be obtained from 
Amicus, relevant IRB/IEC/REB, and regulatory authorities (in accordance with local 
requirements) prior to implementation. 
Protocol deviations that may significantly impact subject safety or scientific integrity 
(eg, changes to eligibility criteria, addition or deletion of tests, dosing, duration of treatment, 
and/or other aspects of study design) are not permitted under GCP or by Amicus, unless 
necessary to eliminate an immediate hazard to the subject(s). Where Amicus and/or the 
investigator must take urgent safety measures to protect subjects from an immediate hazard, a 
protocol deviation may be allowed prior to obtaining approval from the relevant IRB/IEC/REB 
(and/or regulatory authorities) according to 21 Code of Federal Regulations 312.30(b) (2). In 
such cases, Amicus and the IRB/IEC/REB must be notified within 1 business day. 
Amicus and the relevant IRB/IEC/REB, where required by local law, must be informed of all 
protocol deviations and violations, and the investigators shall document such protocol deviations 
and violations in subject source documents and eCRFs. 
16.3.5. 
Delegation of Investigator Duties 
The investigator should ensure that all persons assisting with this study are adequately qualified 
and informed about their study-related duties and functions, the protocol, any amendments to the 
protocol, and the study treatment. 
Amicus will select a coordinating investigator as a representative of all investigators for this 
study. Each investigator 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, the 
designee should have the appropriate medical qualifications to effectively conduct or supervise 

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any potential resuscitation procedures. Even if the investigator delegates any trial-related duties 
to other qualified members of his or her study staff, the investigator retains ultimate 
responsibility for obtaining informed consent from study subjects; for ensuring that the 
investigation is conducted according to the protocol, the signed investigator statement 
(Form FDA 1572 or Statement of Foreign Investigator), and applicable regulations; for 
protecting the rights, safety, and welfare of study subjects; and for the control of investigational 
products under evaluation. 
16.3.6. 
Study and Site Closure 
Upon completion or termination of the study, the Amicus monitor or its designee will conduct 
site closure activities with the investigator or site personnel (as appropriate), in accordance with 
applicable regulations, GCP, and standard operating procedures of Amicus or its designee. 
Amicus reserves the right to temporarily suspend or terminate the study at any time for reasons 
including (but not limited to) safety issues, ethical issues, or severe noncompliance. If Amicus 
determines that such action is required, Amicus will discuss the reasons for taking such action 
with the investigator or head of the medical institution (where applicable). When feasible, 
Amicus will provide advance notice to the investigator or head of the medical institution of the 
impending action. 
If a study is suspended or terminated for safety reasons, Amicus will promptly inform all 
investigators, heads of the medical institutions (where applicable), and/or institutions conducting 
the study. Amicus or its designee will also promptly inform the relevant regulatory authorities of 
the suspension/termination along with the reasons for such action. Where required by applicable 
regulations, the investigator or head of the medical institution must inform the IRB/IEC/REB 
promptly and provide the reason(s) for the suspension/termination. 
16.4. 
Legal and Financial Aspects 
16.4.1. 
Liability and Insurance 
Liability and insurance provisions for this study are provided in separate agreements. 
16.4.2. 
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, miglustat (as in Zavesca), 
Myozyme, Lumizyme, or Amicus, as outlined in the financial disclosure form provided by 
Amicus. The investigator agrees to update this information in case of significant changes during 
the study or 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. 
• 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/REB. 

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Each sub-investigator to whom the investigator delegates significant study-related 
responsibilities will provide financial disclosures. 
16.5. 
Records Retention 
Following closure of the study, the investigator or head of the medical institution (where 
applicable) must maintain all site study records (except for those required by local regulations to 
be maintained elsewhere) in a safe and secure location. The records must be easily accessible 
when needed (eg, for a sponsor audit or regulatory inspection) and must be available for review 
in conjunction with assessment of the facility, supporting systems, and relevant site personnel. 
Where permitted by local laws/regulations or institutional policy, some or all of the records may 
be maintained in a format other than hard copy (eg, microfiche, scanned, and electronic); 
however, caution must be exercised before such action is taken. The investigator must ensure 
that all reproductions are legible and are a true and accurate copy of the original. In addition, 
they must meet accessibility and retrieval standards, including regeneration of a hard copy, if 
required. The investigator must also ensure that an acceptable back-up of the reproductions exists 
and that there is an acceptable quality control procedure in place for creating the reproductions. 
Amicus (or designee) will inform the investigator of the time period for retaining the site records 
in order to comply with all applicable regulatory requirements. The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by local laws/regulations, 
Amicus’ standard operating procedures, and/or institutional requirements. 
The investigator must notify Amicus of any changes in the archival arrangements, including, but 
not limited to, archival of records at an off-site facility or transfer of ownership of the records in 
the event that the investigator is no longer associated with the site. 
16.6. 
Use of Study Findings 
All information concerning the operation of Amicus that has been provided by Amicus and is 
unpublished is confidential and must remain the sole property of Amicus. The investigator agrees 
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. The 
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 and will ensure that the study 
findings are reported in a manner that complies with applicable requirements for reporting 
clinical study results. The final analysis will be performed for the final CSR based on a data 
cutoff date of 31 December 2024. Any data collected after this date will be provided as an 
addendum to the final CSR when all subjects have completed the study or have been withdrawn 
from the study. 

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17. 
REFERENCES 
Enright, P.L. and Sherrill D.L. (1998). "Reference equations for the six-minute walk in healthy 
adults." Am J Respir Crit Care Med 158(5 Pt 1):1384-1387. 
Hagemans, M. L. C., A. C. J. W. Janssens, L. P. F. Winkel, K. A. Sieradzan, A. J. J. Reuser, 
P. A. Van Doorn and A. T. Van der Ploeg (2004). "Late-onset Pompe disease primarily affects 
quality of life in physical health domains." Neurology 63(9): 1688-1692. 
Hirschhorn, R. and A. J. J. Reuser (2001). Glycogen Storage Disease Type II: Acid 
α-Glucosidase (Acid Maltase) Deficiency. The Metabolic and Molecular Bases of Inherited 
Disease. C. Scriver, A. Beaudet, W. Sly and D. Valle. New York, McGraw-Hill. 
2006: 3389-3420. 
Kishnani, P. S., R. D. Steiner, D. Bali, K. Berger, B. J. Byrne, L. E. Case, J. F. Crowley, 
S. Downs, R. R. Howell, R. M. Kravitz, J. Mackey, D. Marsden, A. M. Martins, 
D. S. Millington, M. Nicolino, G. O’Grady, M. C. Patterson, D. M. Rapoport, A. Slonim, 
C. T. Spencer, C. J. Tifft and M. S. Watson (2006). "Pompe disease diagnosis and management 
guideline." Genet Med 8(5): 267-288. 
Leslie, N. and L. Bailey (2017). Pompe Disease. GeneReviews(R). R. A. Pagon, M. P. Adam, 
H. H. Ardinger et al. Seattle (WA): 1993-2017. 
Raben, N., P. Plotz and B. J. Byrne (2002). "Acid α-Glucosidase deficiency (glycogenosis 
type II, Pompe disease)." Current Molecular Medicine 2(2): 145-166. 
Sampson, H. A., A. Muñoz-Furlong, R. L. Campbell, N. F. Adkinson Jr, S. A. Bock, A. Branum, 
S. G. A. Brown, C. A. Camargo Jr, R. Cydulka, S. J. Galli, J. Gidudu, R. S. Gruchalla, 
A. D. Harlor Jr, D. L. Hepner, L. M. Lewis, P. L. Lieberman, D. D. Metcalfe, R. O’Connor, 
A. Muraro, A. Rudman, C. Schmitt, D. Scherrer, F. E. R. Simons, S. Thomas, J. P. Wood and 
W. W. Decker (2006). "Second symposium on the definition and management of anaphylaxis: 
Summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium." Journal of Allergy and Clinical Immunology 
117(2): 391-397. 
Schoser, B., A. Stewart, S. Kanters, A. Hamed, J. Jansen, K. Chan, M. Karamouzian and 
A. Toscano (2017). "Survival and long-term outcomes in late-onset Pompe disease following 
alglucosidase alfa treatment: a systematic review and meta-analysis." J Neurol 264(4): 621-630. 
Toscano, A. and B. Schoser (2013). "Enzyme replacement therapy in late-onset Pompe disease: a 
systematic literature review." J Neurol 260(4): 951-959. 
van der Ploeg, A. T., P. R. Clemens, D. Corzo, D. M. Escolar, J. Florence, G. J. Groeneveld, 
S. Herson, P. S. Kishnani, P. Laforet, S. L. Lake, D. J. Lange, R. T. Leshner, J. E. Mayhew, 
C. Morgan, K. Nozaki, D. J. Park, A. Pestronk, B. Rosenbloom, A. Skrinar, C. I. van Capelle, 
N. A. van der Beek, M. Wasserstein and S. A. Zivkovic (2010). "A randomized study of 
alglucosidase alfa in late-onset Pompe’s disease." N Engl J Med 362(15): 1396-1406. 
Vogel, WH (2010). "Infusion reactions: diagnosis, assessment, and management." Clin J Oncol 
Nurs Apr; 14(2):E10-21. 

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Wyatt, K., W. Henley, L. Anderson, R. Anderson, V. Nikolaou, K. Stein, L. Klinger, D. Hughes, 
S. Waldek, R. Lachmann, A. Mehta, A. Vellodi and S. Logan (2012). "The effectiveness and 
cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of 
people with lysosomal storage disorders." Health Technology Assessment 16(39): 1-543. 

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APPENDIX 1. NEW UPDATED STUDY DESIGN FOR AMENDMENT 3 
7. 
OBJECTIVE 
The objective of this amendment is to continue collecting long-term safety and efficacy data on 
LOPD subjects treated with cipaglucosidase alfa/miglustat while decreasing some of the burden 
on those subjects taking part, and continuing to provide treatment where regulatory approval has 
not yet been granted or the product is not yet commercially available. 
8. 
INVESTIGATIONAL PLAN 
8.1. 
Study Design 
This is a multicenter, international, open-label extension study of cipaglucosidase alfa/miglustat 
in adult subjects with LOPD who completed Study ATB200-03. No additional subjects will be 
enrolled after data cutoff date of 31 December 2024. 
Upon approval of this amendment, any subjects continuing in the study will follow the updated 
Schedule of Assessments in Table 10. 
Upon approval of this amendment, study visits that include minimal efficacy, safety, and other 
assessments will be scheduled approximately every 52 weeks. These visits may occur over 
2 days, provided all study assessments and procedures are performed before administration of 
study drug. The relevant IRBs, ECs, and REBs should be notified of any deviations from the 
protocol. 
Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function 
(6MWT) and pulmonary function tests (FVC). Safety assessments include monitoring of AEs, 
including IARs, vital signs, physical examinations including weight. Concomitant medications 
and nondrug therapies will also be recorded. 
The study will continue until one of the conditions outlined in Section 8.2 in the main body of 
the protocol is met. 
9. 
SUBJECT SELECTION AND WITHDRAWAL CRITERIA 
Please refer to Section 9 in the main body of the protocol. 
10. 
TREATMENT OF SUBJECTS 
Please refer to Section 10 in the main body of the protocol. 
11. 
STUDY DRUG MATERIALS AND MANAGEMENT 
Please refer to Section 11 in the main body of the protocol. 

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12. 
STUDY PARAMETERS AND PROCEDURES 
12.1. 
Schedule of Assessments 
A Schedule of Assessments showing each study assessment and procedure along with the 
scheduled time of occurrence is provided for subjects who continue in the study upon approval 
of this protocol amendment (Table 10). 
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, in the 
eCRF. 
Visits may occur over 2 days; if assessments are not able to be completed in 2 days, an additional 
day may be scheduled. Once established, every effort should be made to maintain the order of 
procedures, approximately at the same time of day, at each study visit throughout the study, 
regardless of the number of days that are used for the visit. 
If an infusion (or infusions) were missed close to the scheduled assessments at any of the study 
visits, it should be communicated with the Amicus Medical Monitor to determine on a case by 
case basis whether catch-up infusions are needed and how many catch-up infusions are needed 
prior to the study assessments. The rationale for the missed infusion should be captured. 
For additional details on study visits and description of study assessments, please refer to 
Section 12.2 and Section 12.3. 

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Table 10: 
Schedule of Assessments for Subjects Who Continue Under Protocol Amendment 3 
 
Treatment 
Follow-up 
Study Visit 
Infusion Visits  
(Every 2 Weeks 
Through EOS/ET) 
Every 52 Weeksa 
EOS/ET 
≥ 30 Days After 
Last Dose 
Visit Window (Days) 
± 3 
± 3 
± 3 
± 3 
Schedule next visit 
X 
X 
X 
 
Clinical Assessment 
Concomitant medications and nondrug therapies (12.3.3) 
X 
X 
X 
X 
Complete PEb (12.3.4) 
 
X 
X 
 
Vital signs (12.3.6) 
X 
X 
X 
 
Weightc (12.3.5) 
 
X 
X 
 
AEs/SAEs, including IARs (13) 
X 
X 
X 
X 
12-lead ECGd (12.3.10) 
 
X 
X 
 
Serum chemistry, hematologyd (12.3.11.1) 
 
X 
X 
 
Urine pregnancy teste (12.3.11.2) 
X 
X 
X 
 
Pulmonary Function Tests 
FVC (sitting, supine) (12.3.16) 
 
X 
X 
 
Motor Function Assessments 
6MWT (12.3.18) 
 
X 
X 
 

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Table 10: 
Schedule of Assessments for Subjects Who Continue Under Protocol Amendment 3 (Continued) 
 
Treatment 
Follow-up 
Study Visit 
Infusion Visits  
(Every 2 Weeks 
Through EOS/ET) 
Every 52 Weeksa 
EOS/ET 
≥ 30 Days After 
Last Dose 
Visit Window (Days) 
± 3 
± 3 
± 3 
± 3 
Study Drug Administration 
Miglustat (10) 
Every 2 weeks 1 hour before infusion of cipaglucosidase alfa 
 
Cipaglucosidase alfa (10) 
Every 2 weeks 
 
Abbreviations: 6MWT = 6-minute walk test; AE = adverse event; ECG = electrocardiogram; EOS = end of study; ET = early termination; FVC = forced vital 
capacity; IRT = interactive response technology; PE = physical examination; SAE = serious adverse event 
a Study visits will be scheduled every 52 weeks until study termination by the sponsor. 
b Complete physical examinations will include assessment of head, ears, eyes, nose, throat (HEENT), respiratory, cardiovascular, lymphatic, gastrointestinal, and 
neurologic systems. 
c Weight will be entered into the IRT system every 52 weeks for calculation of cipaglucosidase alfa dose. 
d Test to be performed locally. 
e Urine pregnancy tests are performed locally only for female subjects of childbearing potential. If the urine pregnancy test has a positive result, study drug will 
not be administered and a confirmatory serum pregnancy test will be performed. 

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13. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
Please refer to Section 13 in the main body of the protocol. 
14. 
DATA MANAGEMENT 
Please refer to Section 14 in the main body of the protocol. 
15. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
15.1. 
Endpoints 
15.1.1. 
Safety Endpoints 
The long-term safety profile of cipaglucosidase alfa/miglustat will be characterized using 
incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug, frequency and 
severity of immediate and late IARs, and any abnormalities noted in other safety assessments 
(eg, clinical laboratory tests, ECGs, vital signs). Immunogenicity to cipaglucosidase alfa will 
also be described. 
15.1.2. 
Efficacy Endpoints 
Efficacy measures are as follows: 
• 6MWD 
• 6MWD (% predicted) 
• sitting FVC (% predicted) 
15.2. 
Sample Size Considerations 
No formal sample size calculation was performed for this open-label extension study. The 
maximum sample size for this study is based on the number of subjects who complete 
Study ATB200-03, which has a target enrollment of 110 subjects. 
15.3. 
Data Analysis Considerations 
The Statistical Analysis System (SAS®) version 9.4 (or latest version at the time of the analysis) 
and R© software will be used for all statistical procedures and analyses. 
Full details of the data and analysis methods will be provided in the statistical analysis plan. 
15.3.1. 
Analysis Populations 
The open-label extension remaining safety (OLE-RS) population includes all subjects who 
remained in the open-label extension study ATB200-07 and continued to receive treatment under 
this amendment. The OLE-RS population will be used for all analyses (including safety and 
efficacy). 

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15.3.2. 
Treatment Groups 
There will be a single treatment group to be analyzed following this amendment, and that is the 
subjects who remained in the OLE study under Protocol Amendment 3. 
15.3.3. 
Statistical Methods 
15.3.3.1. Interim Analyses 
Not applicable. 
15.3.3.2. Adjustment for Multiple Comparisons/Multiplicity 
No adjustment for multiplicity will be performed. All analyses will be descriptive. 
15.3.3.3. Missing Data Handling 
For all efficacy endpoints based on patient-reported outcome/clinical outcome assessment 
instruments, the scoring algorithms (including the standard or published data imputation or 
pro-rating methods contained in the scoring algorithms) will be implemented. 
No data imputation are planned for missing efficacy data. If any imputations are decided upon 
later, the details will be provided in the statistical analysis plan. 
In general, missing safety data will not be imputed. However, attributes such as missing dates for 
AEs and concomitant medications will be imputed using similar methods as described for 
ATB200-03 in order to ensure consistency. Details will be provided in the statistical analysis 
plan. 
15.3.3.4. Windowing Conventions 
By-visit assessments for safety and efficacy will be summarized based on visit windows. 
15.3.3.5. Statistical Tests 
No formal hypotheses are planned to be tested. Unless otherwise specified, only descriptive 
statistics will be presented. Any inferential analyses will be presented for summary purposes. 
Where appropriate, 2-sided 95% confidence intervals will also be provided for summary 
purposes. 
15.3.3.6. Common Calculations 
In general, continuous variables will be summarized using descriptive statistics (the number of 
subjects with available data, mean, standard deviation, median, minimum, and maximum). 
Categorical variables will be summarized using counts and percentages. 
15.3.4. 
Analyses 
All analyses under this amendment will be based only on the stand-alone additional data 
collected following the database lock (DBL) for the final CSR, and there will be no integration 
with any data that existed prior to the DBL. 

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In general, continuous data will be summarized using descriptive statistics, and categorical data 
will be summarized using counts and percentages. Specific analysis details and display format 
will be described in the statistical analysis plan. 
15.3.4.1. Efficacy Analyses 
In general, continuous data will be summarized using descriptive statistics, and categorical data 
will be summarized using counts and percentages, as described above in Section 15.3.3.6. 
Specific analysis details and display format will be described in the statistical analysis plan. 
15.3.4.1.1. Analyses of Ambulatory Function and Pulmonary Function 
Efficacy variables (6MWD [m]), percent predicted 6MWD, and percent predicted sitting FVC) 
will be summarized over time for the assessment visits that occurred post-DBL of the final CSR, 
based on the OLE-RS population. Where a change from baseline summary is required, the 
baseline result will be based on the last assessment prior to the DBL of the final CSR. A 95% 
confidence interval for the mean change from baseline will be provided where applicable. For 
the analysis of percent predicted 6MWD, the predicted value will be calculated using the 
reference equations from Enright and Sherill (Enright and Sherill 1998). 
15.3.4.2. Safety Analyses 
Safety data will be summarized on the OLE-RS population. Visit-based safety variables will be 
summarized over time for the assessment visits that occurred post-DBL of the final CSR. Where 
change from baseline or percent change from baseline summaries are required, the baseline 
results will be based on the last assessment made prior to the DBL of the final CSR. 
Safety data will be summarized using descriptive statistics for continuous data and using counts 
and percentages for categorical data, as described in Section 15.3.3.6. 
Exposure to study medication will be calculated in weeks and analyzed as continuous variables 
using descriptive statistics. In addition, the duration of exposure will be categorized and a 
frequency distribution of the categories (each summarized by count and percentage) will be 
presented. 
An overall summary of incidence of AEs (which includes the total number of TEAEs, total 
number of serious TEAEs as well as the total number of subjects) will be presented. The number 
and percentage of subjects who experienced nonserious TEAEs as well as serious TEAEs will be 
summarized by preferred term within system organ class. The summary of nonserious and 
serious TEAEs will also be presented by intensity (mild, moderate, severe), as well as by 
relationship to study medication. In addition, the number of AEs (as opposed to the number and 
percentage of subjects) will be presented. 
Serious adverse events, including deaths, will be summarized and listed. Separate listings of 
death, SAEs (treatment-emergent and nontreatment-emergent), and discontinuations due to AEs 
will be provided. 
Summaries and listings will also be provided for deaths, SAEs, and AEs leading to 
discontinuation and infusion-associated reactions. Adverse events will be coded using Medical 
Dictionary for Regulatory Activities version 18 or higher. 

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Clinical laboratory results, ECG parameters, and vital signs will be summarized using descriptive 
statistics (number, mean, median, standard deviation, minimum, and maximum) by treatment 
group and visit for actual values and changes from baseline. The proportion of subjects with 
abnormalities will be provided for clinical laboratory results, ECGs, and vital signs. Shift tables 
will also be provided for clinical laboratory results. 
Concomitant medications and nondrug therapies will be summarized by treatment group. 
Concomitant medications terms will be coded using the World Health Organization Drug 
Dictionary (September 2013 DDE). 
16. 
STUDY CONDUCT CONSIDERATIONS 
Please refer to Section 16 in the main body of the protocol. 

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APPENDIX 2. SAMPSON CRITERIA FOR ANAPHYLAXIS 
 
Source: Sampson, Muñoz-Furlong et al. 2006 

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APPENDIX 3. POTENTIALLY CLINICALLY SIGNIFICANT 
GUIDELINES 
Criteria for identifying abnormalities as potentially clinically significant are based on the 
Guidelines for the Division of Neuropharmacological Drug Products, US Food and Drug 
Administration (revised on 2 April 1987). The laboratory values identified below are not 
inclusive of all the safety laboratory analytes that will be assessed during this clinical trial. Safety 
laboratory analytes that are known to be elevated in some adults with Pompe disease 
(eg, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase) and safety 
laboratory analytes which are not listed below will be reviewed to determine if they are to be 
noted as potentially clinically significant based on the magnitude of the out of range value as 
compared with the normal range and the subject’s baseline value, and whether the out of range 
value is coded as clinically significant by the principal investigator. 

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Laboratory Values 
Variable 
Criterion Values 
 
Standard Units 
SI Units 
Chemistry 
SGOT (AST) 
≥ 3 x Upper Limit Normal 
 
SGPT (ALT) 
≥ 3 x Upper Limit Normal 
 
Alkaline Phosphatase 
≥ 3 x Upper Limit Normal 
 
LDH 
≥ 3 x Upper Limit Normal 
 
BUN 
≥ 30 mg/dL 
≥ 10.7 μM 
Creatinine 
≥ 2.0 mg/dL 
≥ 176.8 μM 
Uric Acid 
Male 
≥ 10.5 mg/dL 
≥ 624.6 μM 
 
Female 
≥ 8.5 mg/dL 
≥ 505.6 μM 
Bilirubin (Total) 
≥ 2.0 mg/dL 
≥ 34.2 μM 
Hematology 
Hematocrit 
Male 
≤ 37% 
 
 
Female 
≤ 32% 
 
Hemoglobin 
Male 
≤ 11.5 g/dL 
 
 
Female 
≤ 9.5 g/dL 
 
Platelets 
≤ 75,000/mm3 or ≥ 700,000/mm3 ≤ 75 x 109/L or ≥ 700 x 109/L 
Leukocytes 
≤ 2,800/mm3 or ≥ 16,000/mm3 
≤ 2.8 x 109/L or ≥ 16 x 109/L 
Eosinophils 
≥ 10% 
 
Neutrophils 
≤ 15% 
 
Urinalysis 
Protein 
Increase of ≥ 2 units 
 
Glucose 
Increase of ≥ 2 units 
 
Casts 
Increase of ≥ 2 units 
 
Abbreviations: BUN = blood urea nitrogen; LDH = lactate dehydrogenase; SGOT (AST) = serum glutamic 
oxaloacetic transaminase (aspartate aminotransferase); SGPT (ALT) = serum glutamic pyruvic transaminase 
(alanine aminotransferase) 

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Vital Sign Values 
Variable 
Criteria 
 
Change Relative to Baseline 
Heart Rate 
≥ 120 bpm 
and an 
increase of ≥ 15 bpm 
≤ 50 bpm 
and a 
decrease of ≥ 15 bpm 
Systolic Blood Pressure 
≥ 180 mmHg 
and an 
increase of ≥ 20 mmHg 
≤ 90 mmHg 
and a 
decrease of ≥ 20 mmHg 
Diastolic Blood Pressure 
≥ 105 mmHg 
and an 
increase of ≥ 15 mmHg 
≤ 50 mmHg 
and a 
decrease of ≥ 15 mmHg 
Weight 
 
 
change of ≥ 7% body weight 
 
ECG Values 
ECG Parameter 
Low 
High 
PR interval (ms) 
< 120 ms 
≥ 210 ms 
QRS duration (ms) 
≤ 50 ms 
> 120 ms 
QTcB interval (ms) 
Not applicable 
> 450 ms for males and > 470 ms 
for females and QTcB increases 
from baseline > 60 ms (males and 
females) 
Ventricular rate (bpm) 
A decrease from referencea 
≥ 15 bpm, and an absolute value 
< 50 bpm 
An increase from referencea 
≥ 15 bpm, and an absolute value 
> 120 bpm 
Abbreviations: ECG = electrocardiogram; QTcB = QT interval for corrected heart rate 
a Reference value: baseline or initial visit value, as appropriate