An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Intravenous Infusions of ATB200 Co-Administered With Oral AT2221 in Adult Subjects With Pompe Disease
Phase: PHASE1
Conditions: Pompe Disease
Sponsor: Amicus Therapeutics

Official Title: 
An Open-Label, Fixed-Sequence, Ascending-Dose, 
First-in-Human Study to Assess the Safety, 
Tolerability, Pharmacokinetics, Pharmacodynamics, 
and Efficacy of Intravenous Infusions of ATB200 Co-
Administered with Oral AT2221 in Adult Subjects 
With Pompe Disease 
 
 
NCT Number: 
NCT02675465 
 
 
Document Date:  
Amendment 2: 10 January 2019 
 

 
 
CLINICAL STUDY PROTOCOL 
 
AN OPEN-LABEL, FIXED-SEQUENCE, ASCENDING-DOSE, 
FIRST-IN-HUMAN STUDY TO ASSESS THE SAFETY, 
TOLERABILITY, PHARMACOKINETICS, 
PHARMACODYNAMICS, AND EFFICACY OF INTRAVENOUS 
INFUSIONS OF ATB200 CO-ADMINISTERED WITH ORAL 
AT2221 IN ADULT SUBJECTS WITH POMPE DISEASE 
Protocol Number: ATB200-02 
ORIGINAL PROTOCOL: Date: 6 November 2015 
AMENDMENT 01: Date: 16 December 2015 
AMENDMENT 02: Date: 11 February 2016 
AMENDMENT 03: Date: 19 July 2016 
AMENDMENT 04: Date: 16 December 2016 
AMENDMENT 05: Date: 16 February 2018 
AMENDMENT 06: Date: 30 April 2018 
AMENDMENT 07: Date: 03 October 2018 
AMENDMENT 08: Date: 10 January 2019 
EudraCT Number: 2015-004798-34 
US IND Number: 127,387 
 
Compounds: ATB200 and AT2221 
 
Sponsor 
Amicus Therapeutics, Inc. 
1 Cedar Brook Drive 
Cranbury, NJ 08512 
Phone: 609-662-2000 
 
The information in this document is the property of Amicus Therapeutics, Inc. and is strictly 
confidential. Neither the document nor the information contained herein may be reproduced or 
disclosed outside of Amicus Therapeutics, Inc. without the prior written consent of the company.  

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2. 
SUMMARY OF CHANGES TO THE PROTOCOL 
Protocol 
Number 
ATB200-02 
Protocol Title 
An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study 
to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, 
and Efficacy of Intravenous Infusions of ATB200 Co-administered with 
Oral AT2221 in Adult Subjects with Pompe Disease 
The previous version of this protocol (Amendment 7.0, 03 October 2018) was amended to create 
the current version (Amendment 8.0, 10 January 2019). For definitions of abbreviations used, see 
Section 5. 
Protocol History 
Version and Date of Protocol Comments 
Original Protocol, 
06 November 2015 
Original version 
Amendment 1.0,  
16 December 2015  
Addition of the following text: Subjects will be monitored 
for at least 48 hours from the start of each infusion during 
Stage 1 (ie, ERT dose-escalation stage). Since the target 
infusion duration in the study is 4 hours, all subjects will be 
closely monitored for the first 4 hours during their infusion, 
and then observed in hospital for an additional 44 hours prior 
to discharge. Subjects will be admitted and dosed at either an 
infusion center or a hospital and thereafter hospitalized for 
the remainder of the observation period.  
In Stage 2, when subjects have reached their maximum per 
protocol ATB200 dose, all subjects will be monitored for at 
least an additional 2 to 4 hours from the end of their infusion. 
Amendment 2.0,  
11 February 2016 
The protocol was amended to include changes relevant for 
the: 
• Addition of a 24-month, open-label extension 
phase, making this a study conducted in 3 stages, 
with a total duration of 2 years and 18 weeks 
• Roll-over enrollment for subjects who complete 
Stages 1 and 2 (Cohort 1) to the extension stage 
(Stage 3) 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 2.0,  
11 February 2016 
(Continued) 
• Introduction of new cohorts into the study 
− Cohort 1 subjects; defined as adults with 
Pompe disease who have been on ERT for 
2 to 6 years prior to enrollment and are able to 
walk at least 200 meters in the 6MWT 
− Cohort 2 subjects; defined as adults with 
Pompe disease who are wheelchair bound, 
unable to walk unassisted, and have been on 
ERT (alglucosidase alfa) for ≥ 2 years prior to 
enrollment 
− Cohort 3 subjects; defined as adults with 
Pompe disease who have never received 
treatment with ERT and are able to walk at 
least 200 meters in the 6MWT 
• Enrollment of 4 to 6 ERT-experienced 
nonambulatory subjects (Cohort 2) and 4 to 6 
ERT-naïve subjects (Cohort 3) in Stage 3, who 
will receive treatment with 20 mg/kg ATB200 
co-administered with 260 mg AT2221 
• Separate enrollment criteria specified for 
Cohorts 2 and 3 
• Sentinel dosing specified for Cohorts 2 and 3 
• Additional analyses planned for Cohorts 2 and 3 
• Additional objectives for: 
− Assessment of long-term efficacy and safety 
− PK parameters for plasma rhGAA activity and 
total protein and plasma AT2221 in 
ERT-naïve subjects 
• Additional study assessments extending through 
the end of Stage 3 for all cohorts, including 
functional assessments to be performed every 
6 months 
• Change made to the values for AUC0-∞ in 
predicted exposure for single dose administration 
of AT2221 in humans; corrected to 130 mg dose, 
12.35 μg·hr/L and 260 mg dose, 24.71 μg·hr/L 
(see Section 6.4.2, Table 4) 
• Addition of a total GAA protein concentration 
assessment when a blood sample for IgE is 
collected in all stages for all cohorts 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 3.0,  
19 July 2016 
The protocol was amended to include typographical and 
administrative changes to improve the clarity of the 
document. As well as changes relevant to: 
• Removal of Table 1, information supplied in a 
separate document. 
• Clarifications to Inclusion Criterion 5, 6, 14, 15. 
• Clarifications to Exclusion Criterion 1, 9, 11, 12, 
13, 19, 21, 22, 23, 31, 32.  
• Clarification to prohibited medications: 
− Myozyme/Lumizyme after treatment with 
ATB200 has begun. 
− β2-receptor agonists and non-selective 
β-blockers (eg, propranolol, nadalol and 
carvedilol). 
• Clarification to Interim Analysis of up to 
4 interim analysis will be performed in the study. 
• Acceptable methods of contraception for male 
and female subjects enrolled in the study now 
include abstinence and the use of a diaphragm 
combined with a condom. 
• Schedule of Assessments (Table 9, Table 10, 
Table 11, and Table 12) was updated with various 
changes to certain visits due to redundancy of 
assessments. 
• Information previously only contained in the 
Schedule of Assessments table footnotes was also 
added to the text in Section 10.2. 
• Visit windows were added toTable 10, Table 11, 
and Table 12. 
• Vital signs during PK visits have been adjusted 
to: Hours 0, 1, 4, 6, 12, and 24. 
• PK blood sampling Table 13 has been adjusted. 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 3.0,  
19 July 2016 
(Continued) 
• The following text was added to Section 10.1.10 
and Section 10.2.12: Upon study completion or 
subject discontinuation, subjects who are 
confirmed positive for anti-rhGAA antibodies 
will complete follow-up immunological testing 
for up to 6 months (ie, at 1-, 3-, and 6-months 
follow-up). If anti-rhGAA antibodies are not 
confirmed positive at follow-up time points 
earlier than 6 months, no further testing is 
required. 
• Addition of Section 10.4, definition of high 
sustained antibody titer. 
• Addition of the following text in Section 11.1.1: 
Subjects experiencing adverse events should be 
followed until their health has returned to baseline 
status or stabilized or have otherwise been 
explained. 
• Addition of Appendix 7 to include the PGIC and 
SGIC scales. 
Amendment 04,  
16 December 2016 
The protocol was amended to include the following changes: 
• Collection of available historical antibody 
information.  
• Addition of patient reported outcomes and 
functional assessments at the End of PK visit for 
Cohort 1 subjects. 
• Addition of functional assessments at Months 15 
and 21 of Stage 3 for Cohort 1 and to Months 3, 
9, 15, and 21 for Cohorts 2 and 3, which will 
change the frequency of these assessments to 
every 3 months for the duration of Stage 3 for all 
cohorts. 
• Addition of Patient Reported Outcomes at 
Months 15 and 21 of Stage 3 for Cohort 1 and 
Months 3, 9, 15, and 21 for Cohorts 2 and 3, 
which will change the frequency of these 
assessments to every 3 months for the duration of 
Stage 3 for all cohorts. 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 04,  
16 December 2016 
(Continued) 
• Addition of Global Impression of Change 
assessments at Months 6, 12, 15, 18, and 24 of 
Stage 3 for Cohort 1; Months 3, 9, 15, 18, 
and 21 for Cohorts 2 and 3, which will change the 
frequency of these assessments to every 3 months 
for the duration of Stage 3 for all cohorts. 
• Elimination of the requirement for a 6-hour fast 
prior to clinical laboratory testing. 
• Elimination of abstinence as an allowable form of 
birth control. 
• Correction of statistical comparisons for PK data. 
• Clarification of non-assessment visits 
(ie, Infusion Only visits). 
• Clarification of testing procedures at unscheduled 
visits. 
• Subject’s Global Impression of Change form has 
been revised (Appendix 7). 
• Other clarification to improve the readability and 
understanding of the document. 
Amendment 05,  
16 February 2018 
The protocol was amended to include changes relevant to 
the: 
• Implementation of Home Infusion: ERT infusion, 
for eligible subjects who so desire, at the subject’s 
residence, outside the hospital or clinic setting, 
may be considered for subjects, where allowed by 
Principal Investigator, regulatory authorities 
and/or local ethics committees 
• Introduction of a new cohort into the study 
− Additional subjects will be recruited/enrolled 
to Cohort 4; defined as adults with Pompe 
disease who have been on ERT for ≥ 7 years 
and are able to walk at least 200 meters in the 
6MWT. Subjects are assigned to Multiple 
Doses Co-administration of 20 mg/kg 
ATB200 + 260 mg AT2221 as their study 
treatment 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 05,  
16 February 2018 
(Continued) 
• Introduction of a new stage 
− Stage 4; defined Stage 4, treatment period will 
begin at the end of Stage 3 and will continue 
as open-label extension until 
commercialization, study discontinuation or 
subject withdrawal, with functional 
assessments every 6 months 
• Clarification of Study Design: Stage 3  
• Addition of rationale for Retrospective Data 
collection prior to Baseline 
• Updated protocol with preliminary safety PK 
efficacy data 
• Clarification: Changes made to PK sample 
collection and analysis for Cohorts 1 and 3 during 
the study 
• Addition of sparse blood sampling for plasma 
total GAA protein concentrations from Cohorts 1 
and 3 patients 
• Addition of SAE contact information as page 2 of 
the protocol  
• Post-infusion monitoring time changed 
• Addition of follow-up safety visit assessment 
• Clarification: PFTs and/or assessments will be 
performed at the Baseline Visit and every 
3 months in Stage 3 for all ambulatory subjects 
and for nonambulatory subjects without invasive 
ventilatory support 
• Clarification: Reporting under dosing during the 
study 
• Revision: interim analyses will be performed 
during the study as needed 
• Revision: number of subjects (approximately 
21-32 planned) 
• Revision: statistical methods for non-PK-specific 
parameters section 
• Addition of retrospective data collection 
• Table 9 (Treatment Assignment for Stages 1, 2, 3, 
and 4) was updated 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 05,  
16 February 2018 
(Continued) 
• Schedules of Assessments (Table 9, Table 10, 
Table 11, and Table 12) were updated with 
various changes to certain visits due to Stage 4 
assessments  
• Visit windows were added to Table 9, Table 10, 
and Table 12 
• New abbreviated terms and correction of 
omissions 
• Typographical and administrative changes were 
also made to improve the readability and 
understanding of the document 
Amendment 06,  
30 April 2018 
The protocol was amended to include changes relevant to 
the: 
• Clarification of the description, reporting, and 
management of infusion-associated reactions 
(IARs) 
• Updates to the acceptable methods of 
contraception for male and female subjects 
enrolled in the study. Removed use of an IUD 
alone as an acceptable method. 
• Removal of blood sample collection for 
measurement of pro-inflammatory cytokines 
and/or other biomarkers of immune system 
activation for Stage 4 (all Cohorts) and for 
Stage 3, Cohort 4 
• Administrative changes to improve the readability 
and understanding of the document 
Amendment 07, 
03 October 2018 
The protocol was amended to include changes relevant to 
the: 
• Increase in number of subjects in Cohort 4 to 
‘approximately 10 subjects’ 
• Deletion of “with alglucosidase alfa 
(Myozyme/Lumizyme)” in inclusion criterion #29 for 
Cohort 4 
• Increase in upper limit for the 6MWT to 600 meters 
and decrease in lower limit for the 6MWT to 
75 meters in inclusion criterion #32 for Cohort 4 
• Increase in upper limit of upright FVC to 85% in 
inclusion criterion #33 for Cohort 4 

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Protocol History 
Version and Date of Protocol Comments 
Amendment 07, 
03 October 2018 
(Continued) 
• Addition of a UK-specific section to update the 
acceptable methods of contraception for male and 
female subjects enrolled in the study to remove the 
use of double barrier methods as highly effective 
methods of contraception 
• Addition of PROMIS® instruments to the 
Patient-reported Outcomes 
• Addition of activity monitoring to the exploratory 
assessments for Cohort 4 in Stage 3 
• Creation of a separate Schedule of Assessments for 
Cohort 4 
• Increase in sample size from approximately 18 to 
24 subjects to approximately 18 to 34 subjects 
• Update to Section 15: Study Conduct Considerations 
Amendment 08 
10 January 2019 
The protocol was amended to include changes relevant to 
the: 
• Decrease in number of subjects for Cohort 4 from 
approximately 10 subjects to 6 to 8 subjects 
• Update to eligibility for home infusion from 
12 months to 6 months 
• For subjects who are confirmed to have a positive 
result for anti-rhGAA antibodies upon study 
completion or discontinuation, update to follow-up 
immunological testing from 6 months to 12 months 
after the last dose of study drug or until they begin 
treatment with another ERT or investigational therapy 
• Removal of activity monitoring, actigraph from 
Cohort 4 assessments 
• Update to Table 6 and Table 7 to include data through 
Month 18 
• Update to Table 10 and Table 12 to reflect that height 
measurement is taken only at screening 
• Addition of Section 8.8: Criteria for Termination of 
the Study 

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3. 
SYNOPSIS 
Name of Sponsor/Company: Amicus Therapeutics, Inc. 
Names of Investigational Products: ATB200 and AT2221 
Names of Active Ingredients: Recombinant human acid α-glucosidase (rhGAA) and 
miglustat 
Title of Study: An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study to 
Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of 
Intravenous Infusions of ATB200 Co-administered with Oral AT2221 in Adult Subjects with 
Pompe Disease 
Study Center(s): Multicenter, international 
Protocol Number: ATB200-02 
Phase of Development: Phase 1/2 
Objectives:  
Primary 
• To evaluate the safety and tolerability of single-ascending doses of intravenously 
(IV) infused ATB200 
• To evaluate the safety and tolerability of single-ascending doses of IV infused 
ATB200 as a fixed dose, co-administered with ascending oral doses of AT2221 
• To characterize the pharmacokinetics (PK) of single-ascending doses of IV infused 
ATB200  
• To characterize the single- and multiple-dose PK of IV infused 20 mg/kg ATB200 
when co-administered with oral 130 mg or 260 mg AT2221 
• To characterize the PK of single- and multiple-oral doses of 130 mg or 260 mg 
AT2221 when co-administered with IV infused ATB200 
Secondary 
• To evaluate the long-term efficacy of 20 mg/kg of IV infused ATB200 as a fixed 
dose co-administered with oral 260 mg AT2221 in all subjects from Stage 3 
• To evaluate the long-term safety and tolerability of 20 mg/kg of IV infused 
ATB200 as a fixed dose co-administered with oral 260 mg AT2221 in all subjects 
from Stage 3 
• To characterize single- and multiple-dose PK of plasma rhGAA activity and total 
rhGAA protein following IV infused 20 mg/kg ATB200 as a fixed dose 
co-administered with oral 260 mg AT2221 in enzyme replacement therapy 
(ERT)-naïve subjects 

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• To characterize the single- and multiple-dose PK of plasma AT2221 following 
20 mg/kg of IV infused ATB200 co-administered with oral 260 mg AT2221 in 
ERT-naïve subjects 
Exploratory 
To evaluate:  
• Anti-rhGAA antibodies (total and neutralizing) 
• Cross-reactivity of anti-rhGAA antibodies to alglucosidase alfa  
• Pro-inflammatory cytokines and other biomarkers of immune system activation  
• Pharmacodynamic (PD) markers (urine hexose tetrasaccharide [Hex4] and serum 
creatine phosphokinase [CK])  
• Impact of anti-rhGAA antibodies on plasma GAA total protein exposures 
Study Design:  
This is an open-label, fixed-sequence, single- and multiple-ascending dose, first-in-human 
(FIH) study to evaluate the safety, tolerability, PK, PD, and efficacy of intravenous ATB200 
alone and when co-administered with oral AT2221. The study will be conducted in 4 stages. 
Approximately 10 to 12 ERT-experienced (alglucosidase alfa) ambulatory subjects (Cohort 1) 
will be enrolled in Stages 1 and 2. In Stage 1, safety, tolerability, and PK will be evaluated 
following sequential single-ascending doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg of IV 
infused ATB200 administered 2 weeks apart. In Stage 2, safety, tolerability, and PK will be 
evaluated following single- and multiple-ascending dose combinations: 20 mg/kg of IV 
infused ATB200 co-administered with 130 mg of AT2221 administered orally every 14 days 
(± 3 days) for 3 doses, followed by 20 mg/kg of IV infused ATB200 co-administered with 
260 mg of AT2221 administered orally for 3 doses. ERT-experienced ambulatory subjects 
who complete Stages 1 and 2 will enter into a long-term extension stage of the study, 
hereinafter referred to as Stage 3, and will continue to be assessed for safety, tolerability, and 
efficacy of extended treatment with 20 mg/kg of IV ATB200 co-administered with 260 mg of 
AT2221 administered orally. In addition, disease-relevant functional assessments will be 
performed at regular intervals.  
In Stage 3, approximately, 12 to 18 additional subjects will enroll, of whom approximately 
4 to 6 will be ERT-experienced nonambulatory (Cohort 2), 5 will be ERT-naïve ambulatory 
subjects (Cohort 3), and approximately 6 to 8 will be ERT-experienced ambulatory subjects 
who have completed at least 7 years of ERT (Cohort 4). These subjects will be treated with 
20 mg/kg of IV infused ATB200 co-administered with 260 mg of AT2221 administered orally 
every 2 weeks and evaluated for safety, tolerability, PD, and efficacy. Duration of Stage 3 will 
be 2 years.  
Stage 4 treatment period will begin at the end of Stage 3 and continue as an open-label 
extension until subject withdrawal, regulatory approval or marketing authorization and/or 
commercialization in the participating subject’s country, or study termination by the sponsor, 
Amicus Therapeutics, Inc. (Amicus). 

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ERT-naïve subjects will also undergo blood sample collection for single- and multiple-dose 
PK assessments. Based on having previous exposure to ERT, PK assessments are expected to 
be similar in ERT-experienced nonambulatory and ERT-experienced ambulatory subjects. In 
addition, the intensive PK sampling in this study is likely to present an undue burden to 
nonambulatory subjects. For these reasons, no PK assessments will be conducted in 
ERT-experienced nonambulatory subjects. 
ERT-experienced ambulatory subjects are defined as adults diagnosed with Pompe disease 
who have been on ERT for 2 to 6 years (Cohort 1) or ≥ 7 years (Cohort 4), prior to enrollment, 
and who are able to walk at least 200 meters in the 6-Minute Walk Test (6MWT).  
ERT-experienced nonambulatory subjects (Cohort 2), are defined as adults diagnosed with 
Pompe disease who are wheelchair bound and unable to walk unassisted, and have been on 
ERT for ≥ 2 years prior to enrollment.  
ERT-naïve ambulatory subjects (Cohort 3), are defined as adults with Pompe disease who 
have never received treatment with ERT and who are able to walk at least 200 meters in the 
6MWT. 
Table 1: 
Treatment Assignment for Stages 1, 2, 3, and 4 
 
 
 
Cohorts 
Stage 1 
(6 weeks) 
Stage 2 
(12 weeks) 
Stage 3 
(2 years) 
Stage 4  
(Until 
Approval) 
Period 1 
Single-
Dose 
Period 2 
Single-
Dose 
Period 3 
Single-
Dose 
Period 4 
3 Multiple 
Doses 
Co-
administration 
Period 5 
3 Multiple 
Doses  
Co-
administration 
Multiple Dose, 
24 months, 
Extension 
Co-
administration 
Multiple Dose, 
Long-term, 
Extension 
Co-
administration 
Cohort 1 
(n = 11) 
5 mg/kg 
ATB200 
10 mg/kg 
ATB200 
20 mg/kg 
ATB200 
20 mg/kg 
ATB200 + 
130 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Cohort 2 
(n = 4-6) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Cohort 3 
(n = 5) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Cohort 4 
(n = 6-8) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Abbreviations: NA = not applicable 
Note: At least 1 of the 2 sentinel subjects will complete Stage 2, Period 5 and the safety data will be reviewed by 
the Safety Steering Committee (SSC) before dosing any newly enrolled subjects from Cohorts 2 and 3. The first 
2 subjects from Cohorts 2 and 3 will also serve as sentinel subjects for their respective cohorts. 

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Study Procedures 
Subjects in Cohort 1 will participate in Screening, Baseline, Stage 1 (3-period, 
fixed-sequence, single-ascending dose of ATB200 alone), Stage 2 (2-period, fixed-sequence, 
multiple-dose of 20 mg/kg ATB200 co-administered with multiple-ascending doses of 
AT2221), and Stage 3 (a 24-month extension stage with continued dosing of 20 mg/kg 
ATB200 co-administered with 260 mg AT2221) of the study. Stage 4 treatment period will 
begin at the end of Stage 3 and continue as an open-label extension until subject withdrawal, 
regulatory approval or marketing authorization and/or commercialization in the participating 
subject’s country, or study termination by Amicus.  
Subjects in Cohorts 2, 3, and 4 will participate in Screening and Baseline for Stage 3 of the 
study, as well as Stage 3 dosing-visits. Additionally, subjects in Cohort 3 will participate in 
serial 24-hour PK visits. Subjects in Cohort 2 and 4 will not participate in PK analyses. The 
procedures and assessments performed are as follows: 
Screening:  
• At Screening for either Stage 1 or Stage 3, all subjects will provide informed 
consent and undergo review of eligibility criteria. Assessments for all subjects 
include medical history (including forced vital capacity [FVC] and 6MWT, CK, 
alanine aminotransferase [ALT], aspartate aminotransferase [AST], and urine 
Hex4 lab results) and history of falls; review of prior and concomitant medications 
and nondrug therapies; vital signs (heart rate [HR], respiration rate [RR], blood 
pressure [BP], and temperature); height; weight; comprehensive physical 
examination (PE); 12-lead electrocardiogram (ECG); clinical safety laboratory 
assessments (serum chemistry, hematology, and urinalysis); urine pregnancy test; 
and urine sample for Hex4. Blood samples will also be obtained for immunological 
assessments (total and neutralizing antibodies, exploratory pro-inflammatory 
cytokines/other biomarkers of immune system activation, cross-reactivity to 
alglucosidase alfa, and immunoglobulin E [IgE]), exploratory biomarkers of 
Pompe disease, and immunogenicity. For subjects in Cohorts 1, 2, and 4, a history 
of prior infusion-associated reactions (IARs) will also be obtained, and gene that 
encodes human acid α-glucosidase (GAA) genotyping will be performed for those 
who are unable to provide GAA genotyping report at screening. A subject who 
meets all of the inclusion criteria and none of the exclusion criteria will be 
assigned to Stage 1 as described above in Table 1. 
Baseline:  
• Baseline assessments for all subjects include review of eligibility criteria; medical 
history and history of falls, adverse event (AE) and serious AE (SAE) inquiry, 
review of prior and concomitant medications and nondrug therapies; vital signs 
(HR, RR, BP, and temperature); weight; brief PE; ECG; Rasch-built 
Pompe-specific activity (R-PAct) Scale; Rotterdam Handicap Scale (RHS); 
Fatigue Severity Scale (FSS); Patient-reported Outcomes Measurement 
Information System (PROMIS®) for dyspnea, fatigue, physical functioning, and 
upper extremity; pulmonary function tests (PFTs); motor function tests; and 

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muscle strength tests for all subjects. Additionally, a history of IARs will be 
obtained for subjects in Cohorts 1, 2, and 4. 
• Retrospective data for patients from Cohorts 1, 2, and 3: All available data for 
6MWT, pulmonary function tests, other motor function tests such as 10-meter 
walk, 4-stair climb, and Gower's, quantitative (dynamometry) and qualitative 
muscle strength tests, Gait, Stairs, Gower, and Chair maneuver (GSGC) score, and 
patient-reported outcomes (PROs), if available should be recorded in the Electronic 
Data Capture (EDC).  
• Retrospective data will be gathered from subjects in Cohort 4: At least three 
6MWT results, each at least 6 months apart must be available and entered in the 
EDC. At least two 6MWT results should be within the past three years. 
Additionally, pulmonary function tests, other motor function tests such as 10-meter 
walk, 4-stair climb, and Gower's, quantitative (dynamometry) and qualitative 
muscle strength tests, GSGC score, and PROs, if available should be recorded in 
the EDC. In addition to the above requirement, all available data will be collected. 
Stage 1, Periods 1, 2, and 3: 
• Safety: review of AEs, including SAEs and IARs; review of concomitant 
medications and nondrug therapies; vital signs (HR, RR, BP, and temperature); 
brief PE; ECG; clinical safety laboratory assessments (serum chemistry, 
hematology, and urinalysis); and urine pregnancy test. 
• PD: urinary Hex4 and serum CK. 
• Immunological: blood samples for anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive with alglucosidase alfa) and blood samples for measurement of 
pro-inflammatory cytokines and other biomarkers of immune system activation. If 
needed, IgE and total GAA protein concentration will also be measured. 
• Serial 24-hour PK: During Period 1 (Visit 3, Day 1), Period 2 (Visit 4, Day 15), 
and Period 3 (Visit 5, Day 29), blood sampling for plasma human acid 
α-glucosidase (GAA) activity levels and total GAA protein concentrations will be 
taken for all subjects. 
Stage 2, Periods 4 and 5:  
• Safety: review of AEs, including SAEs and IARs; review of concomitant 
medications and nondrug therapies; vital signs (HR, RR, BP, and temperature); 
weight; PE; ECG; clinical safety laboratory assessments (serum chemistry, 
hematology, and urinalysis); and urine pregnancy test. 
• PD: urinary Hex4 and serum CK. 
• Immunological: blood samples for anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive with alglucosidase alfa) and blood samples for measurement of 
pro-inflammatory cytokines and other biomarkers of immune system activation. If 
needed, IgE and total GAA protein concentration will also be measured. 

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• Serial 24-hour PK: During Period 4 (Visit 6, Day 43 and Visit 8, Day 71) and 
Period 5 (Visit 9, Day 85 and Visit 11, Day 113), blood sampling for plasma GAA 
activity levels, total GAA protein concentrations, and AT2221 concentrations will 
be taken for all subjects.  
End of PK: 
• Safety: review of AEs, including SAEs and IARs; review of concomitant 
medications and nondrug therapies; vital signs (HR, RR, BP, and temperature); 
weight; PRO; PFT; motor function; muscle strength tests; PE; ECG; clinical safety 
laboratory assessments (serum chemistry, hematology, and urinalysis); and urine 
pregnancy test. 
• PD: urinary Hex4 and serum CK. 
• Immunological: blood samples for anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive with alglucosidase alfa) and blood samples for measurement of 
pro-inflammatory cytokines and other biomarkers of immune system activation. If 
needed, IgE and total GAA protein will also be measured. 
Stage 3: 
• Safety: review of AEs, including SAEs, as well as IARs; review of concomitant 
medications and nondrug therapies; vital signs (HR, RR, BP, and temperature); 
weight; height; PRO; PE; ECG; clinical safety laboratory assessments (serum 
chemistry, hematology, and urinalysis); and urine pregnancy test.  
• PD: urinary Hex4 and serum CK. 
• Immunological: blood samples for anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive with alglucosidase alfa) and blood samples for measurement of 
pro-inflammatory cytokines and other biomarkers of immune system activation. If 
needed, IgE and total GAA protein concentration will also be measured. 
• Serial 24-hour PK for subjects in Cohort 3 only: single-dose (first administration of 
20 mg/kg ATB200 and 260 mg AT2221), Day 1, and multiple-dose (third 
administration of 20 mg/kg ATB200 and 260 mg AT2221), Week 4 blood samples 
for plasma GAA activity levels, total GAA protein concentrations, and AT2221 
concentrations will be collected. 
• Follow-up sparse blood sampling for plasma total GAA protein will be performed 
after at least 18 months of ATB200/AT2221 treatment. If the subject has 
completed Stage 3, sparse PK sampling will be performed in Stage 4.  
• Global impression of change (Physician Global Impression of Change [PGIC] and 
Subject Global Impression of Change [SGIC]); PFTs; motor function tests; muscle 
strength tests. 

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Stage 4: 
• Safety: review of AEs, including SAEs, as well as IARs; review of concomitant 
medications and nondrug therapies; vital signs (HR, RR, BP, and temperature); 
weight; PE; ECG; clinical safety laboratory assessments (serum chemistry, 
hematology, and urinalysis); and urine pregnancy test.  
• PD: urinary Hex4 and serum CK. 
• Immunological: blood samples for anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive with alglucosidase alfa) and blood samples for measurement of 
pro-inflammatory cytokines and other biomarkers of immune system activation. If 
needed, IgE and total GAA protein concentration will also be measured. 
• Global impression of change (PGIC and SGIC); PFTs; motor function tests; and 
muscle strength tests. 
Subjects who prematurely withdraw from the study will come in for an Early Termination 
(ET) visit and will undergo all of the assessments that are to be performed at the ET/End of 
Study visit. No study treatment will be administered. If any of the sentinel subjects withdraw 
prematurely from the study, that subject will be replaced by the next subject enrolled in the 
study (eg, if Subject 1 withdraws, Subject 3 will replace that subject as a sentinel subject). 
Upon study completion or subject discontinuation, subjects who are confirmed positive for 
anti-rhGAA antibodies will complete 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 1-, 3-, 6-, 9-, and 
12-months follow-up) or until they begin treatment with another ERT or investigational 
therapy. If anti-rhGAA antibodies are not confirmed positive at follow-up time points earlier 
than 6 months, no further testing is required. 
Safety Monitoring 
Safety will be monitored by the Amicus Medical Monitor and the investigators on a 
continuous basis and on a regular basis by a Safety Steering Committee (SSC). The details of 
the membership, meeting schedules, procedures, roles, and responsibilities of the SSC are 
detailed in the SSC Charter.  
Subjects will be monitored in a hospital or infusion center for 48 hours from the start of each 
infusion during Stage 1 (ie, ERT dose-escalation stage). Since the target infusion duration in 
the study is 4 hours, all subjects will be closely monitored for the first 4 hours during their 
infusion and then observed in hospital for an additional 44 hours prior to discharge. Subjects 
will be admitted and dosed at either an infusion center or a hospital and thereafter hospitalized 
for the remainder of the observation period.  
In Stages 2 and 3, all subjects will be monitored at a hospital or infusion center for an 
additional 2 to 4 hours from the end of their infusion. Once a subject has completed 1 year in 
Stage 3, the subjects who have not experienced IARs for the prior 6 months, can be monitored 
for 1 hour from the end of their infusion, at the PI's discretion. Subjects who switch to home 
infusion, must be monitored for 2 to 4 hours after the end of their infusions for a period of at 
least 3 months. If no IARs or other AEs occur during the 3 months, the monitoring can be 
reduced to 1 hour post infusion at the PIs discretion. 

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When at least 1 of the 2 Cohort 1 sentinel subjects has completed Stage 2, Period 5 sentinel 
dosing and the safety data has been reviewed by the SSC, subjects from Cohorts 2 and 3 can 
begin enrollment into Stage 3. The first 2 subjects from Cohorts 2 and 3 will undergo sentinel 
dosing in the same manner as subjects from Cohort 1 during Stage 2. 
Sentinel Dosing 
The first 2 subjects in Cohort 1 of this study will be the sentinel subjects for the study and will 
be the first 2 subjects dosed in each period of the study (Periods 1 to 5). The first 2 subjects 
dosed in each cohort will be the sentinel subjects for that cohort. In the event that a sentinel 
subject is prematurely withdrawn from the study, he/she will be replaced by the next enrolled 
subject in that cohort. 
Note: At least one of the 2 sentinel subjects will complete Period 5, Stage 2 dosing, and all 
available safety data from Cohort 1 subjects will be reviewed by the SSC, before dosing of 
subjects in Cohorts 2 and 3 can be started. The first 2 subjects in Cohorts 2 and 3 will also 
serve as sentinel subjects for their respective cohorts. 
In Stage 1 (Periods 1, 2, and 3), subjects will be dosed with single-ascending doses of 
ATB200 (5 mg/kg [Period 1], 10 mg/kg [Period 2], and 20 mg/kg [Period 3]). 
Following the dosing of the 2 sentinel subjects for each study period in Stage 1, an evaluation 
of the available safety data (PE, vital signs, AEs, infusion reactions, ECG, and available 
locally performed laboratory tests) will be performed within 48 hours by the Amicus Medical 
Monitor and the investigators. The SSC will convene for a formal safety review when central 
safety laboratory data are available for both sentinel subjects at each dose level. If the SSC 
determines that there are no safety concerns that preclude dosing at the dose assigned for that 
period, up to 10 additional Cohort 1 subjects will be enrolled and dosed. 
Note: Vital signs will be monitored as detailed in the Schedule of Assessments tables. For PK 
Visits 3, 4, 5, 6, and 9, vital signs will be monitored at hours 0, 1, 4, 6, 12, and 24 after the 
start of infusion. During the 48-hour observation period, vital signs will be monitored, at a 
minimum, every 6 to 8 hours until the end of the 48-hour observation period. 
The SSC will also convene for a safety review when safety data (including central laboratory 
safety data) for all Cohort 1 subjects at all three Stage 1 dose levels are available.  
Stage 2 (after Visits 6 and 9), safety data from 2 sentinel subjects will be reviewed by the 
SSC, and safety will be assessed after the first dose as for each period in Stage 1. If the SSC 
determines that there are no safety concerns that preclude additional dosing at 20 mg/kg 
ATB200 co-administered with 130 mg AT2221 (Visit 6) or 20 mg/kg ATB200 
co-administered with 260 mg AT2221 (Visit 9), up to 10 additional subjects will receive 
3 biweekly (every other week) doses at the dose assigned for that period. 
The SSC will reconvene when all safety data (including central safety laboratory data) are 
available for all Cohort 1 subjects at the end of Stage 2. 
Stage 3, sentinel dosing will be performed for the first 2 subjects in Cohort 2 and the first 
2 subjects in Cohort 3. If the SSC determines that there are no safety concerns that preclude 
the additional dosing of 20 mg/kg of ATB200 co-administered with 260 mg of AT2221, the 

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remaining 2 to 4 additional subjects in Cohort 2 and the remaining 2 to 4 additional subjects in 
Cohort 3 will be dosed.  
During the long term extension (Stage 3 and Stage 4) the SSC will convene periodically - at 
least 2 times a year. The SSC will also convene ad hoc in case of an SAE/suspected 
unexpected serious adverse reaction (SUSAR) or an identified safety concern.  
The SSC may recommend any of the following review: 
• Continue the study without modifications 
• Continue the study with modifications (amendment) 
• Temporarily halt dosing 
• Permanently stop dosing 
If in the opinion of the SSC there are no AEs or safety concerns in the sentinel subjects that 
might preclude continued study dosing, dosing will continue for all remaining subjects at that 
dose level.  
Subject safety will continue to be closely monitored by the Amicus Medical Monitor and 
study investigators on an ongoing basis, and at regular intervals by the SSC. 
Home Infusion  
Subjects participating in the study will be considered eligible for administration of 
ATB200/AT2221 at their home after 6 months of ATB200/AT2221 infusions in the study and 
without an IAR for a period of 6 months prior to last infusion. Subjects with history of 
recurrent severe or life-threatening IARs including anaphylaxis are not eligible for home 
infusions. 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 Principal Investigator with prior approvals from Institutional Review Boards 
(IRBs)/Ethics Committees (ECs), and Regulatory Authorities (RAs). Administration of 
ATB200/AT2221 will be performed at home for eligible subjects by a trained home infusion 
nurse provided by an Amicus designated home infusion service provider. All subjects 
participating in the Home Infusion, will be required to complete all functional assessments at 
the investigational site as defined in the protocol. 
Number of Subjects (Planned): Approximately 18 to 34 subjects will enroll in the study. 
Approximately 10 to 12 subjects in Cohort 1, 4 to 6 subjects in Cohort 2, 5 subjects in 
Cohort 3, and approximately 6 to 8 subjects in Cohort 4. 
Diagnosis and Eligibility Criteria: At the Screening Visit for Stages 1 and 2, subjects from 
Cohort 1 will be evaluated using the eligibility criteria outlined below. At the Screening Visit 
for Stage 3, subjects from Cohorts 2, 3, and 4 will be evaluated with the eligibility criteria 
outlined below as well. Each subject must meet all of the inclusion criteria and none of the 
exclusion criteria. Waivers of inclusion/exclusion criteria are not permitted. 

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Inclusion/Exclusion Criteria  
Cohort 1 
Inclusion Criteria 
1. Male and female subjects between 18 and 65 years of age, inclusive 
2. Subject must provide signed informed consent prior to any study-related procedures 
3. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
4. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
5. Subject has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for the 
previous 2 to 6 years, inclusive 
6. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a frequency 
of once every other week 
7. Subject has received and completed the last 2 infusions without a drug-related adverse 
event resulting in dose interruption 
8. Subject must be able to walk between 200 and 500 meters on the 6MWT 
9. Upright FVC must be 30% to 80% of predicted normal value 
Exclusion Criteria 
1. Subject has received any investigational therapy including adjunctive therapy for 
Pompe disease, other than alglucosidase alfa within 30 days or 5 half-lives of the 
therapy or treatment, whichever is longer, prior to the Baseline Visit, or anticipates 
doing so during the study 
2. Subject has received treatment with prohibited medications within 30 days of the 
Baseline Visit 
3. Subject, if female, is pregnant or breastfeeding at screening 
4. Subject, whether male or female, is planning to conceive a child during the study 
5. Subject requires invasive ventilatory support  
6. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
7. Subject has a medical or any other extenuating condition or circumstance that may, in 
the opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
8. Subject has a history of anaphylaxis to alglucosidase alfa 
9. Subject has a history of high sustained anti-rhGAA antibodies  
10. Subject has a history of allergy or sensitivity to miglustat or other iminosugars  

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11. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor  
12. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Cohort 2 
Inclusion Criteria 
10. Male and female subjects between 18 and 65 years of age, inclusive 
11. Subject must provide signed informed consent prior to any study-related procedures 
12. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
13. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
14. Subject has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for ≥ 2 years 
15. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a regular or 
set frequency  
16. Subject has received and completed the last 2 infusions without a drug-related adverse 
event resulting in dose interruption 
17. Subject must be wheelchair-bound and unable to walk unassisted 
Exclusion Criteria 
13. Subject has received any investigational therapy, including adjunctive therapy for 
Pompe disease, other than alglucosidase alfa within 30 days or 5 half-lives of the 
therapy or treatment, whichever is longer, prior to the Baseline Visit, or anticipates to 
do so during the study 
14. Subject has received treatment with prohibited medications within 30 days of the 
Baseline Visit  
15. Subject, if female, is pregnant or breastfeeding at screening 
16. Subject, whether male or female, is planning to conceive a child during the study 
17. Subject has a medical or any other extenuating condition or circumstance that may, in 
the opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
18. Subject has a history of anaphylaxis to alglucosidase alfa 
19. Subject has a history of high sustained anti-rhGAA antibodies  
20. Subject has a history of allergy or sensitivity to miglustat or other iminosugars 

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21. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor 
22. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Cohort 3 
Inclusion Criteria 
18. Male and female subjects between 18 and 65 years of age, inclusive 
19. Subject must provide signed informed consent prior to any study-related procedures 
20. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
21. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
22. Subject must be able to walk between 200 to 500 meters on the 6MWT 
23. Upright FVC must be 30% to 80% of predicted normal value 
Exclusion Criteria 
23. Subject has received any ERT, including alglucosidase alfa at any time, or any 
investigational therapy for Pompe disease within 30 days or 5 half-lives of the therapy 
or treatment, whichever is longer, prior to the Baseline Visit, or anticipates doing so 
during the study  
24. Subject has received treatment with prohibited medications within 30 days of the 
Baseline Visit 
25. Subject, if female, is pregnant or breastfeeding at screening 
26. Subject, whether male or female, is planning to conceive a child during the study 
27. Subject requires invasive ventilatory support 
28. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
29. Subject has a medical or any other extenuating condition or circumstance that may, in 
the opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
30. Subject has a history of allergy or sensitivity to miglustat or other iminosugars 
31. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor 
32. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 

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Cohort 4 
Inclusion Criteria 
24. Male and female subjects between 18 and 75 years of age, inclusive 
25. Subject must provide signed informed consent prior to any study-related procedures 
26. Subject has documented 6MWT on three separate occasions, each at least six months 
apart with at least two values in the past three years 
27. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
28. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
29. Subject has received ERT for the previous ≥ 7 years 
30. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme) at a frequency 
of once every other week 
31. Subject has received and completed the last 2 infusions without a drug-related AE 
resulting in dose interruption 
32. Subject must be able to walk between 75 and 600 meters on the 6MWT 
33. Upright FVC must be 30% to 85% of predicted normal value 
Exclusion Criteria 
33. Subject has received any investigational therapy including adjunctive therapy for 
Pompe disease, other than alglucosidase alfa within 30 days or 5 half-lives of the 
therapy or treatment, whichever is longer, prior to the Baseline Visit, or anticipates 
doing so during the study 
34. Subject has received treatment with prohibited medications within 30 days of the 
Baseline Visit 
35. Subject, if female, is pregnant or breastfeeding at screening 
36. Subject, whether male or female, is planning to conceive a child during the study 
37. Subject requires invasive ventilatory support  
38. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
39. Subject has a medical or any other extenuating condition or circumstance that may, in 
the opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
40. Subject has a history of anaphylaxis to alglucosidase alfa 
41. Subject has a history of high sustained anti-rhGAA antibodies  
42. Subject has a history of allergy or sensitivity to miglustat or other iminosugars  

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43. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor  
44. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Investigational Product, Dosage, and Mode of Administration:  
Stage 1 (consists of 3 dosing periods 2 weeks apart for Cohort 1) 
• Period 1: a single-dose IV infusion of 5 mg/kg ATB200  
• Period 2: a single-dose IV infusion of 10 mg/kg ATB200 to all subjects who have 
completed Period 1 
• Period 3: a single-dose IV infusion of 20 mg/kg ATB200 to all subjects who have 
completed Period 2 
Stage 2 (consists of 2 dosing periods, each comprising 3 study treatment doses, 2 weeks apart 
for Cohort 1) 
• Period 4: 130 mg of AT2221 will be administered orally 1 hour before a 
single-dose IV infusion of 20 mg/kg ATB200 to all subjects who have completed 
Period 3 (repeated every 2 weeks for a total of 3 administrations)  
• Period 5: 260 mg of AT2221 will be administered orally 1 hour before a 
single-dose IV infusion of 20 mg/kg ATB200 to all subjects who have completed 
Period 4 (repeated every 2 weeks for a total of 3 administrations) 
Stage 3 (consists of multiple study-dosing, administered every 2 weeks apart for a duration of 
24 months) 
Stage 4 (consists of multiple study-dosing, administered every 2 weeks apart until study 
treatment approval or discontinuation of the program) 
Study treatment for all subjects in Stage 3 will consist of AT2221 administered orally at 
260 mg followed approximately 1 hour later by a single-dose IV infusion of ATB200 at 
20 mg/kg (repeated every 2 weeks for up to 24 months).  
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of 
oral AT2221. 
Total Duration of Study:  
• Screening: up to 4 weeks 
• Stage 1 + Stage 2: 18 weeks 
• Stage 3: 24 months 
• Stage 4: Until completion or drug approval  

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Criteria for Evaluation: 
Primary:  
Safety assessments: 
• PEs 
• Vital signs, including body temperature, RR, HR, and BP  
• AEs, including IARs  
• 12-lead ECG 
• Clinical safety laboratory assessments: serum chemistry, hematology, and 
urinalysis 
PK of plasma ATB200 and AT2221: 
• Plasma GAA activity levels and total GAA protein concentrations PK parameters: 
maximum observed plasma concentration (Cmax), time to reach the maximum 
observed plasma concentration (tmax), area under the plasma-drug concentration 
time curve from Time 0 to the time of last measurable concentration (AUC0-t), area 
under the plasma-drug concentration time curve from Time 0 extrapolated to 
infinity (AUC0-∞), alpha- and beta-phase half-life (t½), total clearance following IV 
administration (CLT), and steady state volume of distribution (Vss)  
• Ratios of plasma GAA activity levels and total GAA protein concentration Cmax, 
AUC0-t, and AUC0-∞ for all dose regimens  
• Plasma AT2221 PK parameters: Cmax, tmax, AUC0-t, AUC0-∞, and t½, apparent total 
clearance of drug following oral administration (CLT/F), and terminal phase 
volume of distribution following oral administration (Vz/F) for each dose level 
• Ratio of plasma AT2221 PK parameters: Cmax, AUC0-t, and AUC0-∞ for each dose 
level 
• Exposure estimates from sparse plasma total GAA protein concentrations after at 
least 18 months on ATB200/AT2221 treatment in Cohorts 1 and 3 patients will be 
compared to exposures after the first and third doses of 20 mg/kg ATB200 + 
260 mg AT2221.  
Functional Assessments (performed at Baseline and every 3 months in Stage 3): 
For Ambulatory Subjects: 
• Motor Function Tests 
− 6MWT 
− 10-Meter Walk Test (10MWT) 
− Gait, Stairs, Gower, and Chair maneuver (GSGC) 
− Timed Up and Go (TUG) 

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• Muscle Strength Test  
− medical research criteria (MRC) and hand-held dynamometer for both upper 
and lower limbs 
• PFTs  
− FVC, maximum inspiratory pressure (MIP), maximum expiratory pressure 
(MEP), and Sniff Nasal Inspiratory Pressure (SNIP)  
For Nonambulatory Subjects: 
• Muscle Strength Test - Upper Limbs Only  
− MRC and hand-held dynamometer performed for upper limbs only  
• PFTs - in subjects without invasive ventilatory support only 
− FVC, MIP, MEP, and SNIP 
Patient-reported Outcomes (performed at Baseline and every 3 months in Stage 3): 
• FSS 
• RHS 
• R-PAct Scale 
• PROMIS instruments for dyspnea, fatigue, physical functioning, and upper 
extremity 
Exploratory: 
• Anti-rhGAA antibodies (total and neutralizing) 
• Cross-reactivity of anti-rhGAA antibodies to alglucosidase alfa  
• Pro-inflammatory cytokines and other biomarkers of immune system activation 
• PD biomarkers: Hex4 and serum CK 
Methods of Analysis: 
Statistical Methods for PK Parameters:  
Details of the analysis methods related to PK parameters will be provided in a stand-alone 
PK Statistical Analysis Plan (PK SAP). In general, basic descriptive statistics will be provided 
for all PK parameters. 
Cohort 1 
• Dose proportionality assessment on GAA activity levels and total GAA protein 
concentration exposure (Cmax, AUC0-t, and AUC0-∞) ratios of 5, 10, and 20 mg/kg 
ATB200 alone. 
• Analysis of variance (ANOVA) on GAA activity levels and total GAA protein 
concentration exposure (Cmax, AUC0-t, and AUC0-∞) ratios of 20 mg/kg ATB200 

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alone versus 20 mg/kg ATB200 + 130 mg AT2221, and versus 20 mg/kg 
ATB200 + 260 mg AT2221. 
• Dose proportionality assessment for exposure ratios (Cmax, AUC0-t, and AUC0-∞) 
between 130 mg and 260 mg AT2221.  
• The effect of immunogenicity results on PK, PD, and safety will be evaluated. 
Further details will be provided in the Statistical Analysis Plan (SAP). 
Cohort 3 
• ANOVA on GAA activity levels and total GAA protein concentration exposure 
(Cmax, AUC0-t, and AUC0-∞) ratios of 20 mg/kg ATB200 + 260 mg AT2221 in 
subjects from Cohort 3 versus 20 mg/kg ATB200 alone in subjects from Cohort 1, 
versus 20 mg/kg ATB200 + 130 mg AT2221 in subjects from Cohort 1, and versus 
20 mg/kg ATB200 + 260 mg AT2221 in subjects from Cohort 1. 
• ANOVA on AT2221 exposure ratios (which will have the same PK parameters) 
for 260 mg AT2221 in subjects from Cohort 3 versus 130 mg AT2221 and 260 mg 
AT2221 in subjects from Cohort 1. 
Statistical Methods for Non-PK-Specific Parameters: 
Details of the analysis methods related to all non-PK-specific parameters will be provided in a 
separate SAP for the study.  
In general, descriptive statistics (n, mean, standard deviation [SD], median, minimum, and 
maximum) will be provided for all efficacy continuous variables. Each cohort will have its 
own baseline, and analysis will be performed by cohort and overall. In addition, summary 
analyses will be performed by combining Cohort 1, 3, and 4 for ambulatory subjects, or by 
combining Cohort 1 and 4 for ERT-experienced subjects. For Cohort 1, the analysis will also 
be provided by treatment dosing regimen. The visit values and the change (and percent 
change) from baseline to the post-baseline assessment will be analyzed by scheduled visit. 
The 95% confidence interval for the mean (and percent mean) change from baseline by 
scheduled visit will be provided for summary purposes only. In addition, the visit values and 
derived values for each subject will be provided in data listings.  
Safety and other variables that are continuous (including vital signs, laboratory assessments, 
and immunogenicity values) will similarly be analyzed using descriptive statistics. Shift tables 
will be generated for safety laboratory parameters. 
Summary statistics will be provided for all variables that are not PK parameters. 
Adverse events and other variables that are categorical will be summarized using counts and 
percentage. In addition, categorical variables (excluding AEs) will be summarized by 
scheduled visits. 
Interim Analyses: Interim analyses will be performed during the study as needed. Details for 
the interim analysis will be included in the SAP. 

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4. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
DECLARATIONS OF SPONSOR AND INVESTIGATOR .......................................3 
1.1. 
Declaration of Sponsor .................................................................................................3 
1.2. 
Declaration of Investigator ...........................................................................................3 
2. 
SUMMARY OF CHANGES TO THE PROTOCOL ..................................................4 
3. 
SYNOPSIS .................................................................................................................12 
4. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............29 
5. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................36 
6. 
INTRODUCTION AND STUDY RATIONALE ......................................................41 
6.1. 
Pompe Disease ............................................................................................................41 
6.2. 
Pharmacokinetics of Miglustat ...................................................................................42 
6.2.1. 
Use of Miglustat as a Pharmacological Chaperone ....................................................43 
6.2.1.1. 
Effect of Miglustat on Plasma GAA Activity of Alglucosidase Alfa ........................43 
6.2.1.2. 
Characterization of Plasma Miglustat With Alglucosidase Alfa in Subjects 
with Pompe Disease ....................................................................................................43 
6.3. 
ATB200 ......................................................................................................................43 
6.3.1. 
Nonclinical Summary of ATB200 ..............................................................................43 
6.4. 
Dose Rationale ............................................................................................................45 
6.4.1. 
Toxicology and Toxicokinetic Support for Proposed Doses ......................................45 
6.4.2. 
Human Dosing Rationale ............................................................................................46 
6.4.2.1. 
Dose Selection for Co-administered ATB200/AT2221 .............................................47 
6.4.2.2. 
Predicted Safety Margins for Co-administered ATB200/AT2221 .............................48 
6.4.2.3. 
PK Data from the ATB200-02 Study .........................................................................49 
6.4.2.4. 
GAA Protein Using Signature Peptide(s) T09/T50 ....................................................49 
6.4.2.5. 
ATB200 Exposure Stopping Criteria ..........................................................................50 
6.4.2.6. 
ATB200 Preliminary Efficacy Data ...........................................................................50 
7. 
OBJECTIVES AND PURPOSE .................................................................................52 
7.1. 
Primary Objectives .....................................................................................................52 
7.2. 
Secondary Objectives .................................................................................................52 
7.3. 
Exploratory Objectives ...............................................................................................52 
8. 
INVESTIGATIONAL PLAN .....................................................................................53 

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8.1. 
Study Design ...............................................................................................................53 
8.2. 
Safety Monitoring and Sentinel Dosing .....................................................................54 
8.3. 
Pharmacokinetic Sampling Details .............................................................................56 
8.4. 
Details of Study Treatment .........................................................................................57 
8.5. 
Stopping Criteria .........................................................................................................58 
8.6. 
Concomitant Medications and Nondrug Therapies ....................................................59 
8.7. 
Prohibited Medications ...............................................................................................59 
8.8. 
Criteria for Termination of the Study .........................................................................60 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................61 
9.1. 
Number of Subjects ....................................................................................................61 
9.2. 
Eligibility Criteria .......................................................................................................61 
9.2.1. 
Inclusion and Exclusion Criteria ................................................................................61 
9.3. 
Withdrawal Criteria ....................................................................................................65 
9.4. 
Replacement of Subjects .............................................................................................66 
9.5. 
Subjects of Reproductive Potential .............................................................................66 
10. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................68 
10.1. 
Description of Study Visits .........................................................................................98 
10.1.1. 
Screening Visit ............................................................................................................98 
10.1.2. 
Baseline .......................................................................................................................98 
10.1.3. 
Stage 1, Period 1 (Visit 3, Day 1), Period 2 (Visit 4, Day 15), and Period 3 
(Visit 5, Day 29) (Cohort 1 Subjects Only) ................................................................98 
10.1.4. 
Stage 2, Period 4: Visit 6 (Day 43), Visit 7 (Day 57), and Visit 8 (Day 71) 
(Cohort 1 Subjects Only) ............................................................................................99 
10.1.5. 
Stage 2, Period 5: Visit 9 (Day 85), Visit 10 (Day 99), and Visit 11 
(Day 113) (Cohort 1 Subjects Only) ...........................................................................99 
10.1.6. 
End of PK: Visit 12 (Day 127) ...................................................................................99 
10.1.7. 
Stage 3: PK Sampling for Cohort 3 Subjects ..............................................................99 
10.1.8. 
Stage 3: Sparse PK Sampling for Cohorts 1 and 3 Subjects .....................................100 
10.1.9. 
Stage 4: Open-label Extension ..................................................................................100 
10.1.10. 
Early Termination Visit/End of Study ......................................................................100 
10.1.11. 
Follow-up Period ......................................................................................................100 
10.1.12. 
Unscheduled Visits ...................................................................................................100 
10.2. 
Description of Study Assessments ............................................................................101 

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10.2.1. 
Informed Consent .....................................................................................................101 
10.2.2. 
Demographics ...........................................................................................................101 
10.2.3. 
Medical History, Fall History, and Prior Medications .............................................101 
10.2.4. 
Adverse Events and/or Serious Adverse Events .......................................................101 
10.2.5. 
Concomitant Medications and Nondrug Therapies ..................................................102 
10.2.6. 
Vital Signs, Weight, and Height ...............................................................................102 
10.2.7. 
Physical Examination ...............................................................................................102 
10.2.8. 
Electrocardiogram .....................................................................................................102 
10.2.9. 
Patient-reported Outcomes (Including Pompe-associated Scales) ...........................103 
10.2.10. 
Global Impression of Change ...................................................................................103 
10.2.11. 
Clinical Safety Laboratory Tests ..............................................................................103 
10.2.11.1. Serum Chemistry ......................................................................................................103 
10.2.11.2. Hematology ...............................................................................................................104 
10.2.11.3. Urinalysis ..................................................................................................................104 
10.2.12. 
Immunogenicity Assessments ..................................................................................105 
10.2.13. 
Pro-inflammatory Cytokines and Other Biomarkers of Immune System 
Activation .................................................................................................................105 
10.2.14. 
GAA Genotyping .......................................................................................................105 
10.2.15. 
Pharmacokinetic Blood Sampling ............................................................................105 
10.2.16. 
Aliquot of Infusion Solution .....................................................................................106 
10.2.17. 
Pregnancy Test ..........................................................................................................106 
10.2.18. 
Urinary Hex4 ............................................................................................................106 
10.2.19. 
Pulmonary Function Tests (PFTs)/Spirometry .........................................................107 
10.2.20. 
Motor Function Tests – Ambulatory Subjects Only .................................................107 
10.2.20.1. 6-Minute Walk Test (6MWT) ..................................................................................107 
10.2.20.2. Gower’s Maneuver ...................................................................................................107 
10.2.20.3. Timed Up and Go (TUG) .........................................................................................107 
10.2.20.4. 10-Meter Walk Test (10MWT) ................................................................................107 
10.2.20.5. 4-Stair Climb ............................................................................................................108 
10.2.20.6. Gait, Stairs, Gower, and Chair Maneuver (GSGC) Score ........................................108 
10.2.21. 
Muscle Strength Tests – All Subjects .......................................................................108 
10.3. 
Biological Specimen .................................................................................................108 
10.4. 
High Sustained Antibody Titer .................................................................................108 

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10.5. 
Infusion Only Visits ..................................................................................................108 
10.6. 
Home Infusion ..........................................................................................................109 
11. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ................................110 
11.1. 
Definitions ................................................................................................................110 
11.1.1. 
Adverse Events .........................................................................................................110 
11.1.2. 
Serious Adverse Events ............................................................................................110 
11.1.3. 
Infusion-associated Reactions ..................................................................................111 
11.2. 
Relationship to Study Treatment ..............................................................................114 
11.3. 
Assessment of Intensity ............................................................................................115 
11.4. 
Reporting Adverse Events ........................................................................................115 
11.4.1. 
Reporting Serious Adverse Events ...........................................................................116 
11.4.2. 
Additional Reporting Requirements for Suspected Unexpected Serious 
Adverse Reaction ......................................................................................................117 
11.4.3. 
Additional Reporting Requirements for Serious Adverse Reaction .........................117 
11.5. 
Study Treatment Interruptions/Discontinuation Due to an Adverse Event ..............118 
11.6. 
Other Reporting Situations .......................................................................................118 
11.6.1. 
Pregnancy .................................................................................................................118 
11.6.2. 
Overdose/Underdose .................................................................................................118 
12. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ...........................120 
12.1. 
Endpoints ..................................................................................................................120 
12.1.1. 
Primary Endpoints ....................................................................................................120 
12.1.2. 
Secondary Endpoints ................................................................................................121 
12.1.3. 
Exploratory Endpoints ..............................................................................................121 
12.2. 
Hypotheses ................................................................................................................122 
12.3. 
Sample Size Considerations .....................................................................................122 
12.4. 
Data Analysis Considerations ...................................................................................122 
12.4.1. 
Analysis Populations ................................................................................................122 
12.4.2. 
Interim Analyses .......................................................................................................122 
12.4.3. 
PK/PD Analysis ........................................................................................................122 
12.4.3.1. 
Drug Concentration Data ..........................................................................................122 
12.4.3.2. 
PK Parameters ..........................................................................................................122 
12.4.4. 
Statistical Methods ....................................................................................................124 
12.4.4.1. 
Statistical Plan for PK Data ......................................................................................124 

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12.4.4.2. 
Efficacy Analyses .....................................................................................................125 
12.4.4.3. 
Safety Analyses ........................................................................................................125 
12.4.4.4. 
Immunological Analyses ..........................................................................................126 
12.4.4.5. 
Baseline Demographic and Subject Characteristics .................................................126 
12.4.4.6. 
Subject Disposition ...................................................................................................127 
13. 
STUDY TREATMENTS ..........................................................................................128 
13.1. 
Description of Study Treatments ..............................................................................128 
13.2. 
Packaging and Labeling ............................................................................................128 
13.3. 
Study Treatment Administration ..............................................................................128 
13.3.1. 
ATB200 ....................................................................................................................128 
13.3.2. 
AT2221 .....................................................................................................................129 
13.4. 
Study Treatment Accountability ...............................................................................129 
13.5. 
Handling, Storage, Return, and Disposal of Study Treatment .................................129 
14. 
STUDY MANAGEMENT .......................................................................................131 
14.1. 
Documentation of Protocol-required Information and Study Findings ....................131 
14.1.1. 
Electronic Case Report Form Completion ................................................................131 
14.2. 
Data Management .....................................................................................................131 
14.3. 
Safety Steering Committee (SSC) ............................................................................132 
14.4. 
Study Monitoring, Source Data Verification, and Onsite Audits .............................132 
14.5. 
Records Retention .....................................................................................................132 
14.6. 
Use of Study Findings ..............................................................................................133 
14.7. 
Study Close-out ........................................................................................................134 
15. 
STUDY CONDUCT CONSIDERATIONS .............................................................135 
15.1. 
Posting of Information on Publicly Available Clinical Trial Registers ....................135 
15.2. 
Ethical and Legal Aspects ........................................................................................135 
15.2.1. 
Subject Information and Informed Consent .............................................................135 
15.2.2. 
Ongoing Information for IEC/IRB ...........................................................................136 
15.2.3. 
Compliance With Good Clinical Practice (GCP) .....................................................136 
15.2.3.1. 
Quality Control .........................................................................................................136 
15.2.3.2. 
Quality Assurance .....................................................................................................136 
15.2.4. 
Subject Data Protection ............................................................................................137 
15.3. 
Clinical Study Protocols and Amendments ..............................................................137 
15.4. 
Delegation of Investigator Duties .............................................................................137 

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15.5. 
Liability and Insurance .............................................................................................138 
15.6. 
Financial Disclosure .................................................................................................138 
15.7. 
Protocol Adherence ..................................................................................................138 
16. 
REFERENCES .........................................................................................................139 
APPENDIX 1. 
SAMPSON CRITERIA FOR ANAPHYLAXIS .............................................141 
APPENDIX 2. 
POTENTIALLY CLINICALLY SIGNIFICANT GUIDELINES ..................142 
APPENDIX 3. 
RASCH-BUILT POMPE-SPECIFIC ACTIVITY (R-PACT) SCALE ...........145 
APPENDIX 4. 
ROTTERDAM HANDICAP SCALE (RHS) ..................................................146 
APPENDIX 5. 
FATIGUE SEVERITY SCALE (FSS) ............................................................148 
APPENDIX 6. 
PROMIS INSTRUMENTS ..............................................................................149 
APPENDIX 7. 
PATIENT-REPORTED OUTCOMES: AVAILABLE LANGUAGES .........153 
APPENDIX 8. 
PHYSICIAN GLOBAL IMPRESSION OF CHANGE (PGIC) AND 
SUBJECT GLOBAL IMPRESSION OF CHANGE (SGIC) ..........................154 
 
LIST OF TABLES 
Table 1: 
Treatment Assignment for Stages 1, 2, 3, and 4 .........................................................14 
Table 2: 
List of Abbreviations and Specialized Terms .............................................................36 
Table 3: 
Predicted PK of Single-dose Administration of ATB200 in Humans ........................47 
Table 4: 
Predicted Exposure for Single-dose Administration of AT2221 in Humans .............47 
Table 5: 
Predicted Safety Margins for Co-administered ATB200/AT2221 in Humans ..........48 
Table 6: 
Change in 6MWT Distance in Meters in Cohorts 1 and 3 Subjects Through 
Month 18 .....................................................................................................................51 
Table 7: 
Change in Percentage Predicted Sitting FVC (%) in Cohorts 1 and 3 Subjects 
Through Month 18 ......................................................................................................51 
Table 8: 
Treatment Assignment for Stages 1, 2, 3, and 4 .........................................................57 
Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects ...............................69 
Table 10: Schedule of Assessments for Stages 3 and 4, Cohort 1 Subjects ...............................75 
Table 11: Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects ...............................79 
Table 12: Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects ...............................84 
Table 13: Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects ...............................90 
Table 14: Pharmacokinetic Blood Sampling (Cohorts 1 and 3) .................................................95 
Table 15: Sparse Pharmacokinetic Blood Sampling ...................................................................97 
Table 16: Serum Chemistry Parameters ...................................................................................104 

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Table 17: Hematology Parameters ............................................................................................104 
Table 18: Urinalysis Parameters ...............................................................................................104 
Table 19: Guidelines for Management of Immediate Infusion-associated Reactions ..............112 
Table 20: Investigational Product .............................................................................................128 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic .............................................................................................57 
 

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5. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialized terms are used in this study protocol. 
Table 2: 
List of Abbreviations and Specialized Terms 
Term or 
Abbreviation 
Definition 
4-MU-α-Glc 
4-methylumbelliferyl-α-D-glucopyranoside 
6MWT 
6-Minute Walk Test 
10MWT 
10-Meter Walk Test 
AE 
adverse event 
Alglucosidase 
alfa 
active ingredient drug substance name for Lumizyme® and Myozyme®; 
aglucosidase alfa is produced by recombinant DNA technology in a 
Chinese hamster ovary cell line 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
AST 
aspartate aminotransferase 
AT2221 
N-butyldeoxynojirimycin; iminosugar which is used as a pharmacological 
chaperone to ATB200 (a recombinant human acid α-glucosidase) 
ATB200 
recombinant human acid α-glucosidase (rhGAA) enzyme with optimized 
carbohydrate structures, including mannose 6-phosphate (M6P), to 
enhance uptake and delivery of active ATB200 to lysosomes 
ATB200/AT2221 ATB200 co-administered with AT2221 
AUC 
area under the plasma drug concentration time curve 
AUC0-t 
area under the plasma drug concentration time curve from time zero to 
observed time (t) 
AUC0-∞ 
area under the plasma drug concentration-time curve from time zero 
extrapolated to infinite time 
BLQ 
below the limit of quantification 
BP 
blood pressure 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CI-MPR 
cation-independent mannose 6-phosphate receptor 
CL 
clearance 
CLT 
total clearance following IV administration 

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Table 2: 
List of Abbreviations and Specialized Terms (Continued) 
Term or 
Abbreviation 
Definition 
CLT/F 
total clearance following oral administration 
CK 
creatine phosphokinase 
Cmax 
maximum observed plasma concentration 
CRO 
contract research organization 
CS 
clinically significant 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ERT 
enzyme replacement therapy  
ERT-experienced 
for the purposes of this study, this refers to subjects previously treated 
with alglucosidase alfa for at least 2 years prior to enrollment 
ERT-naïve 
For the purposes of this study, this refers to subjects who have not been 
previously treated with alglucosidase alfa 
ET 
early termination 
EU 
European Union 
FSS 
Fatigue Severity Scale; a patient-reported outcomes scale to assess level 
of fatigue and impact of quality of life related to disease or illness 
FIH 
first-in-human 
FVC 
forced vital capacity 
Gaa 
gene encoding (non-human) acid α-glucosidase 
GAA 
human acid α-glucosidase, may be specified as either GAA enzyme 
activity or GAA protein 
GAA 
gene that encodes human acid α-glucosidase  
GAA activity 
GAA activity refers to the active enzyme activity measured using 
4-MU-α-Glc substrate; represents both endogenous GAA and exogenous 
rhGAA  
GCP 
Good Clinical Practice 
GSGC 
Gait, Stairs, Gower, and Chair maneuver; a clinical outcome assessment 
scoring system to assess motor function in Pompe disease 

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Table 2: 
List of Abbreviations and Specialized Terms (Continued) 
Term or 
Abbreviation 
Definition 
Hex4 
hexose tetrasaccharide; commonly designated as Glc4, representing a 
biochemical entity (Glc-a-1-6 Glc-a1-4 Glc-a-1-4Glc) determined in urine 
or plasma as a marker of active glycogen metabolism 
HR 
heart rate 
IAR 
infusion-associated reaction 
ICH 
International Conference on Harmonisation 
IEC 
International Ethics Committee 
IgE 
immunoglobulin E 
IOPD 
infantile-onset Pompe disease 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
KO 
knock-out 
LAMP1 
lysosome-associated membrane protein 1 
ln 
natural log 
LOPD 
late-onset Pompe disease 
Lumizyme® 
commercially available rhGAA (also referred to as alglucosidase alfa) 
M6P 
mannose 6-phosphate 
MEP 
maximum expiratory pressure; a measure of the strength of respiratory 
muscles, obtained by having the patient exhale as strongly as possible 
against a mouthpiece 
MIP 
maximum inspiratory pressure; the inspiratory pressure generated against 
a completely occluded airway. It is used to evaluate inspiratory respiratory 
muscle strength especially diaphragm 
MRC 
medical research criteria 
Myozyme® 
commercially available rhGAA; also referred to as alglucosidase alfa 
NA 
not applicable 
NHP 
non-human primate 
NOAEL 
no-observed-adverse-effect-level 
PAS 
Periodic Acid Schiff  
PD 
pharmacodynamic 

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Table 2: 
List of Abbreviations and Specialized Terms (Continued) 
Term or 
Abbreviation 
Definition 
PE 
physical examination 
PFT 
pulmonary function test 
PGIC 
Physician Global Impression of Change 
PK 
pharmacokinetic 
PRO 
patient-reported outcome 
PROMIS® 
Patient-reported Outcomes Measurement Information System 
rhGAA 
recombinant human acid α-glucosidase 
R-PAct scale 
Rasch-built Pompe-specific Activity scale 
RR 
respiration rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SGIC 
Subject Global Impression of Change; patient response scale rating 
overall improvement ranging from very much improved to very much 
worse 
SNIP 
Sniff Nasal Inspiratory Pressure; a non-invasive assessment of inspiratory 
muscle (diaphragm) strength 
SSC 
Safety Steering Committee 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
terminal half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach the maximum observed concentration 
TUG 
Timed Up and Go; a timed test used to assess mobility 
ULN 
upper limit of normal 
US 
United States 
Vz/F 
terminal phase volume of distribution following oral administration 
Vss  
steady state volume of distribution 
WHO 
World Health Organization 

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Table 2: 
List of Abbreviations and Specialized Terms (Continued) 
Term or 
Abbreviation 
Definition 
Specialized Terms 
Cohort 1  
ERT-experienced ambulatory subjects (Defined as adults with Pompe 
disease who have been on ERT for 2 to 6 years prior to enrollment, and 
are able to walk at least 200 meters in the 6MWT.) 
Cohort 2 
ERT-experienced nonambulatory subjects (Defined as adults with Pompe 
disease who are wheelchair bound and unable to walk unassisted, and 
have been on ERT (alglucosidase alfa) for ≥ 2 years prior to enrollment.) 
Cohort 3 
ERT-naïve ambulatory subjects (Defined as adults with Pompe disease 
who have never received treatment with ERT and are able to walk at least 
200 meters in the 6MWT.) 
Cohort 4 
ERT-experienced ambulatory subjects (Defined as adults with Pompe 
disease who have been on ERT for at least 7 years prior to enrollment, and 
are able to walk at least 75 meters in the 6MWT.) 

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6. 
INTRODUCTION AND STUDY RATIONALE 
6.1. 
Pompe Disease 
Pompe disease, also known as acid maltase deficiency or glycogen storage disease type II, is an 
autosomal recessive genetic disorder caused by mutations in the gene that encodes acid 
α-glucosidase (GAA), an enzyme that catalyzes the breakdown of lysosomal glycogen. Pompe 
disease is also classified as a neuromuscular disease or a metabolic myopathy. It has an estimated 
global incidence of 1:40000 (Martiniuk, Chen et al. 1998; Ausems, Verbiest et al. 1999; 
Hagemans, Winkel et al. 2005a; Kemper, Hwu et al. 2007). Deficiency of GAA leads to the 
accumulation of glycogen in various tissues, particularly in striated muscles resulting in a broad 
spectrum of clinical manifestations that may present during infancy (infantile-onset Pompe 
disease [IOPD]) or in childhood, adolescence, or adulthood (late-onset Pompe disease [LOPD]). 
Earlier onset of disease and lower enzymatic activity are generally associated with a more severe 
clinical course (Kishnani, Steiner et al. 2006). The clinical features of the disease include 
progressive muscle weakness, respiratory insufficiency, and, in the case of IOPD, marked 
cardiomegaly, hepatomegaly, and cardiac failure (Hirschhorn and Reuser 2001; van der Ploeg 
and Reuser 2008). Late-onset Pompe disease can present at any age older than 12 months and is 
characterized by a lack of cardiac involvement and better short-term prognosis (Hirschhorn and 
Reuser 2001; Muller-Felber, Horvath et al. 2007; van der Ploeg and Reuser 2008). The 
symptoms are related to progressive skeletal muscle dysfunction. Proximal lower limb and 
paraspinal trunk muscles are usually affected first, followed by involvement of the diaphragm 
and accessory muscles of respiration. In some cases, diaphragmatic weakness may be evident 
before any other significant weakness is noted (Hagemans, Janssens et al. 2004; Hagemans, 
Winkel et al. 2005b). Most subjects with Pompe disease eventually progress to physical 
debilitation requiring the use of a wheelchair and assisted ventilation, with premature death often 
occurring due to respiratory failure (Hagemans, Janssens et al. 2004; Hagemans, Winkel et al. 
2005a). 
Management of Pompe disease includes enzyme replacement therapy (ERT) with recombinant 
human α-glucosidase (rhGAA), cardiopulmonary and gastrointestinal support, musculoskeletal 
and functional rehabilitation, and dietary therapy. Alglucosidase alfa is the only ERT approved 
for the treatment of Pompe disease. In subjects with IOPD, treatment with alglucosidase alfa has 
been shown to significantly improve survival compared to historical controls (Myozyme Package 
Insert 2010). In LOPD, alglucosidase alfa has been shown to have a statistically significant, 
albeit modest, effect on the 6-Minute Walk Test (6MWT) and forced vital capacity (FVC) 
compared to placebo (Myozyme Package Insert 2010). However, the majority of subjects either 
remain stable or continue to deteriorate while on alglucosidase alfa. The reason for the apparent 
sub-optimal effect of ERT is unclear, but could be partly due to the poor tissue targeting of the 
current ERT, development of anti-rhGAA neutralizing antibodies, or the progressive nature of 
underlying muscle pathology. The effect of alglucosidase alfa is less clear for subjects who are 
already nonambulatory or receiving ventilatory support. The United States (US) product label 
includes a black box warning with information on the potential risk of hypersensitivity reaction. 
Life-threatening anaphylactic reactions, including anaphylactic shock, have been observed in 
subjects treated with alglucosidase alfa.  

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This study is designed to evaluate the effect of a more efficiently targeted rhGAA (ATB200) 
with optimized glycosylation co-administered with a chaperone (AT2221) that has been shown 
to increase the stability of ERT during circulation. Additionally, the study is designed to evaluate 
safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of 
ATB200 co-administered with AT2221 in adult subjects with Pompe disease.  
6.2. 
Pharmacokinetics of Miglustat  
AT2221 (miglustat) capsules contain the same active ingredient in Zavesca® (Actelion 
Pharmaceuticals US Inc.), which is approved for the treatment of Type 1 Gaucher disease, and in 
that disease, it functions as a competitive and reversible inhibitor of the enzyme 
glucosylceramide synthase and it reduces the rate of glycosphingolipid biosynthesis (Zavesca 
Package Insert 2008). The PK of miglustat has been well characterized in subjects with Gaucher 
disease. In this study, AT2221 acts as a pharmacological chaperone to enhance the activity of 
ATB200. AT2221 is administered at a lesser frequency (1 dose every 2 weeks) in contrast to 
dosing with miglustat for Gaucher disease (3 times daily). Treatment assignments for this study 
are outlined in Table 8. 
Absorption: After a 100 mg oral dose of miglustat, the time maximum observed plasma 
concentration of miglustat (tmax) ranged from 2 to 2.5 hours in Gaucher patients. Plasma 
concentrations show a bi-exponential decline, characterized by a short distribution phase and a 
longer elimination phase. The effective half-life of miglustat is approximately 6 to 7 hours, 
which predicts that steady-state will be achieved by 1.5 to 2 days following the start of three 
times daily dosing. 
Miglustat, dosed at 50 and 100 mg three times daily in Gaucher patients, exhibits dose 
proportional pharmacokinetics. The pharmacokinetics of miglustat were not altered after 
repeated dosing three times daily for up to 12 months. In healthy subjects, co-administration of 
Zavesca with food results in a decrease in the rate of absorption of miglustat (maximum plasma 
concentration [Cmax] was decreased by 36% and tmax delayed 2 hours) but had no statistically 
significant effect on the extent of absorption of miglustat (area-under-the-plasma-concentration 
time curve [AUC] was decreased by 14%). The mean oral bioavailability of a 100 mg miglustat 
capsule is about 97% relative to an oral solution administered under fasting conditions. The 
pharmacokinetics of miglustat were similar between adult type 1 Gaucher disease patients and 
healthy subjects after a single dose administration of miglustat 100 mg (Zavesca 
Labeling-Package Insert 2014). The absolute bioavailability of miglustat was approximately 
80% (Wraith and Imrie 2009). 
Distribution: Miglustat does not bind to plasma proteins. Mean apparent volume of distribution 
of miglustat is 83 to 105 liters in Gaucher patients. At steady state, the concentration of miglustat 
in cerebrospinal fluid of six non-Gaucher patients was 31.4% to 67.2% of that in plasma, 
indicating that miglustat crosses the blood brain barrier (Zavesca Labeling-Package Insert 2014). 
Metabolism and Excretion: The major route of excretion of miglustat is via kidney. Following 
administration of a single dose of 100 mg 14C-miglustat to healthy volunteers, 83% of the 
radioactivity was recovered in urine and 12% in feces. In healthy subjects, 67% of the 
administered dose was excreted unchanged in urine over 72 hours. The most abundant metabolite 
in urine was miglustat glucuronide accounting for 5% of the dose. The terminal half-life (t½) of 
radioactivity in plasma was 150 hours, suggesting the presence of one or more metabolites with a 

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prolonged half-life. The metabolite accounting for this observation has not been identified, but 
may accumulate and reach concentrations exceeding those of miglustat at steady state. Miglustat 
did not inhibit or induce substrates of cytochrome P450 enzymes (Zavesca Labeling-Package 
Insert 2014). 
6.2.1. 
Use of Miglustat as a Pharmacological Chaperone 
Miglustat, the active ingredient in AT2221, is a small molecule acting as a pharmacological 
chaperone and has been shown to bind and stabilize GAA to improve its pharmacological 
properties. Two clinical studies (Section 6.2.1.2) evaluating the co-administration of miglustat 
with the current approved ERT (alglucosidase alfa) in Pompe disease have been reported in 
literature. 
6.2.1.1. 
Effect of Miglustat on Plasma GAA Activity of Alglucosidase Alfa 
In a clinical trial conducted in 13 subjects with Pompe disease (3 IOPD and 10 LOPD) at 
4 treatment centers in Italy, 20 to 40 mg/kg alglucosidase alfa was administered alone and then 
co-administered with 4 doses of 80 mg/m2 miglustat. The results of the study showed a mean 
6.8-fold increase in GAA activity exposure (measured in terms of AUC) for co-administration 
compared to alglucosidase alfa alone (Parenti, Andria et al. 2015). 
6.2.1.2. 
Characterization of Plasma Miglustat With Alglucosidase Alfa in Subjects with 
Pompe Disease 
A study conducted at the University of Florida evaluated the PK of plasma miglustat when 
co-administered with intravenous (IV) infusion of alglucosidase alfa to subjects with Pompe 
disease. Preliminary plasma miglustat PK data following the third dose of 100 mg miglustat 
administered 3 times on the day of alglucosidase alfa infusion and 200 mg miglustat 
administered as a single-dose on the day of alglucosidase alfa infusion are available. Generally, 
the plasma PK of miglustat in subjects with Pompe disease was similar to that reported in 
subjects with Gaucher disease. Plasma miglustat exposures were approximately dose 
proportional. Cmax values following 100 mg and 200 mg were 1120 ng/mL and 2450 ng/mL, 
respectively, and area under the plasma concentration time curve from Time 0 to the time of last 
measurable concentration (t) (AUC0-t) values were 8587 ng∙hr/mL and 16092 ng∙hr/mL, 
respectively. Miglustat reached peak concentrations at approximately 3 hours after single-dose 
administration, and the t1/2 ranged from 4.5 to 6.0 hours. Volume of distribution ranged from 
78 to 94 L (Doerfler, Kelley et al. 2014).  
6.3. 
ATB200 
6.3.1. 
Nonclinical Summary of ATB200 
ATB200, which is considered a next-generation rhGAA and is expressed in a new Chinese 
hamster ovary cell line, is manufactured using a process that yields significantly higher 
mannose 6-phosphate (M6P) content compared to the current standard of care for Pompe disease, 
alglucosidase alfa.  
While alglucosidase alfa provides some clinical benefits, the infused enzyme shows insufficient 
uptake in key disease-relevant muscles, which is likely due to an inadequate glycosylation of 

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alglucosidase alfa with M6P, a carbohydrate that binds the cation-independent 
mannose 6-phosphate receptors (CI-MPR) at the cell surface for enzyme internalization and 
lysosome targeting. Studies show that ATB200 has optimized glycosylation with considerable 
amounts of Bis-M6P N-glycans for high-affinity binding to the CI-MPR and targeting to the 
lysosome compared to alglucosidase alfa. The functional benefit of improved affinity of ATB200 
for CI-MPR is shown by its improved cellular uptake in fibroblasts derived from subjects with 
Pompe disease and rat skeletal muscle myoblasts. These studies show that high alglucosidase 
alfa concentrations are required for effective cellular uptake of the exogenous ERT in Pompe 
fibroblasts while substantially lower ATB200 concentrations are needed for efficient cellular 
uptake.  
As previously demonstrated, the tolerability and exposure of alglucosidase alfa ERT was 
improved with co-administration of the pharmacological chaperone miglustat (designated as 
AT2221 in current study) (Doerfler, Kelley et al. 2014; Parenti, Moracci et al. 2014). These data 
suggest that ATB200 may also be improved by co-administering with AT2221. Recombinant 
human acid α-glucosidase enzymes, including ATB200, are not stable at neutral pH and can be 
irreversibly inactivated. Addition of AT2221 prevents this irreversible inactivation of rhGAA. 
In vitro data suggest that AT2221 binds and physically stabilizes ATB200, which prevents 
denaturation and irreversible inactivation of the exogenous enzyme, thus improving the exposure 
and efficacy of ATB200.  
The effect of AT2221 on ATB200 exposure was evaluated in a 13-week combination toxicity 
study with AT2221 (175 mg/kg, administered orally) and ATB200 (100 mg/kg, administered via 
2-hour infusion) administered to non-human primates (NHPs). AT2221 co-administration 
30 minutes prior to ATB200 infusion showed an approximate 2-fold increase in ATB200 
exposure (AUC) and an approximate 2-fold increase in the effective t1/2 of ATB200 as compared 
to IV administration of 100 mg/kg of ATB200 alone.  
Several efficacy studies were conducted in gene encoding (non-human) acid α-glucosidase (Gaa) 
knock-out (KO) mice (the Pompe mouse model) to determine the ability of ATB200 to reduce 
glycogen levels in skeletal muscles compared to alglucosidase alfa and also to determine the 
effects of co-administration of AT2221 on ATB200-mediated glycogen reduction. For this 
purpose, 14- to 16-week-old male Gaa KO mice were administered 2 biweekly (every other 
week) IV bolus injections of 20 mg/kg ATB200. Groups of mice were orally administered 
various doses of AT2221 (1, 3, 5, 10, 20, and 30 mg/kg) 30 minutes before each IV bolus 
injection of ATB200. As a comparator, another group of mice was administered 20 mg/kg 
alglucosidase alfa. Significantly greater glycogen reduction was seen with 20 mg/kg ATB200 
compared to alglucosidase alfa at the same dose (confirming in vitro results of improved M6P 
content in ATB200 leading to improved uptake into target cells). Importantly, co-administration 
with AT2221 further improved (up to 2-fold) the ATB200-mediated glycogen reduction in a 
dose-related manner. Of all the AT2221 doses tested in Gaa KO mice, co-administration of 
10 mg/kg AT2221 with 20 mg/kg ATB200 was the most optimal combination that led to greatest 
glycogen reduction compared to ATB200 alone.  
The targeted delivery of ATB200 into the lysosomes was further confirmed histologically by 
Periodic Acid Schiff (PAS) staining and transmission electron microscopic. The PAS staining of 
skeletal muscles demonstrated the presence of glycogen in the form of intense, magenta 
punctates that were abundant in every muscle fiber of untreated mice. Unlike alglucosidase alfa 

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(20 mg/kg), which showed only a mild improvement of reduction of signal (indicative of reduced 
glycogen), ATB200 (20 mg/kg) alone led to a significant decrease in PAS signals and 
co-administration with AT2221 (10 mg/kg) resulted in a further reduction in substrate, as 
evidenced by the clearance of PAS signals in most muscle fibers. The transmission electron 
microscopic examination of Epon-embedded quadriceps sections also reconfirmed PAS 
observations indicating maximal reduction with co-administered ATB200 and AT2221, as not 
only was the number and size of substrate-containing lysosomes reduced, but also the electron 
density of remaining lysosomes were reduced. Finally, the lysosomal proliferation that is 
considered one of the hallmarks of Pompe disease was also tested by immunohistochemistry 
staining and indicated that, in the muscles examined (quadriceps, heart, and diaphragm), the 
number and size of lysosome-associated membrane protein 1 (LAMP1)-positive vesicles 
(ie, lysosomes) were greatly increased in untreated Gaa KO mice compared to age-matched 
wild-type animals. Notably, a marked decrease in the LAMP1 immunohistochemistry signal 
generally was observed following administration of ATB200 but not with alglucosidase alfa. 
Co-administration with AT2221 led to a further reduction in lysosome proliferation, whereby the 
level and pattern of LAMP1 in the majority of muscle fibers returned to those observed in 
wild-type animals. In general, the effect of co-administration of AT2221 with ATB200 on 
LAMP1 appears to closely mimic the positive effects that were noted for glycogen levels using 
PAS staining. Overall, the histology data are in alignment with the biochemical assessment of 
glycogen reduction.  
Taken together, these data demonstrate that the higher M6P content of ATB200 enables better 
lysosomal targeting, which translates to greater glycogen reduction, and this effect can be further 
improved by the co-administration of ATB200 with AT2221, thus warranting clinical 
investigation of this next-generation treatment for Pompe disease.  
6.4. 
Dose Rationale 
6.4.1. 
Toxicology and Toxicokinetic Support for Proposed Doses 
To support the safety of ATB200, two 6-month Good Laboratory Practice (GLP) repeat-dose 
toxicology studies were conducted with ATB200 by IV administration, one in rats and one in 
NHPs. To support the safety of ATB200 co-administered with AT2221, a 3-month GLP 
co-administration toxicity study was conducted in NHPs with ATB200 administered IV and 
AT2221 administered orally by nasogastric gavage. 
Across all 3 studies, no gender differences in exposure were noted. For all tested doses, plasma 
ATB200 concentration was measurable to ≥ 24 hours after dosing, while plasma AT2221 
concentration was measureable to 74.5 hours after dosing (evaluated only in the 13-week 
co-administration study). For ATB200, as expected, exposure was lower when determined 
according to active protein levels, compared to the exposure based on total protein; however, 
across all studies, exposure increased as the dose increased. Little to no accumulation of either 
ATB200 or AT2221 was observed upon repeat (once every other week) administration. Finally, 
in animals administered ATB200, high anti-drug antibodies were noted, and with a certain 
animals developing neutralizing antibodies. Importantly, anti-drug antibodies/neutralizing 
antibodies did not affect ATB200 exposure or ATB200 toxicokinetic parameters. Of note, 
co-administration of ATB200/AT2221 in NHPs resulted in decreased ATB200 clearance (CL) 
and increased plasma exposure by approximately 2-fold relative to ATB200 monotherapy. 

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No treatment-related overt signs of toxicity were noted in any of the 3 studies, nor were any 
adverse, treatment-related hematological or clinical chemistry findings observed. Slight changes 
in several clinical pathology parameters noted in the rat study (ie, increased white blood cells, 
lymphocytes, basophils, and calcium, and decreased glucose) for the mid and high dose animals 
that may have been related to treatment, but the changes were not considered adverse or 
toxicologically significant based on their slight magnitude, the lack of any corresponding effect 
on the animals’ general condition, and the absence of correlated changes in histopathology. No 
treatment-related effects on the safety pharmacology parameters, organ weights, or gross and 
microscopic findings were observed in any of these studies. The no-observed-adverse-effects 
level (NOAEL) for the 2 repeat dose studies was 200 mg/kg, the highest dose tested. In rats, the 
AUC0-t and Cmax (combined genders) were 21,150 μg•hr/mL and 5,490 μg/mL, respectively, on 
Day 169 (averaged total protein). In NHPs, the AUC0-t and Cmax (combined genders) were 
25,000 μg∙hr/mL and 4,205 μg/mL, respectively, on Day 169 (averaged total protein). The 
NOAEL in the co-administration toxicity study in NHPs was 100 mg/kg for ATB200 and 
175 mg/kg for AT2221, the highest doses tested. At the highest tested doses of 
ATB200/AT2221, the AUC0-t and Cmax (combined genders) were 13,850 μg∙hr/mL and 
2,270 μg/mL, respectively, for ATB200 (Day 85; averaged total protein) and 216 μg∙hr/mL and 
22 μg/mL, respectively, for AT2221 (Day 85).  
Two in vitro assays were conducted using the final clinical formulation of ATB200, an in vitro 
hemolysis assay and an in vitro flocculation assay, both using human whole blood. The assays 
assessed the hemolytic potential of ATB200 in human whole blood (hemolysis assay) and its 
compatibility with human serum and plasma (flocculation assay). The dose range tested in both 
assays spanned the expected Cmax values for clinical IV administration 2 and 4 hours in duration. 
No evidence of hemolysis or flocculation was noted up to the highest concentration tested of 
1,000 μg/mL, which is more than 2-fold higher than the anticipated Cmax at the predicted 
therapeutic dose of 20 mg/kg. 
6.4.2. 
Human Dosing Rationale 
To predict ATB200 exposure in humans, a PK model assessing the concentration versus time 
profile of ATB200 activity was developed based on PK data collected in Gaa KO mice and 
NHPs (Section 6.4.1). The resulting 2-compartment model with linear elimination adequately 
characterized the concentration versus time profile of ATB200 activity for all dose levels across 
multiple animal species. The model included a theoretical allometric component accounting for 
species-specific differences in CL and the volume of distribution (Vd) to predict PK parameters 
and ATB200 exposure in humans. The PK model also integrated data for rhGAA activity 
following IV administration of 20 mg/kg alglucosidase alfa. Using the PK model, the predicted 
CL and Vd of ATB200 in a typical 70 kg human subject are 0.768 L/hr and 2.41 L, respectively. 
The CL of ATB200 is expected to be approximately 30% faster than the CL of alglucosidase alfa 
in humans. The faster CL of ATB200 likely reflects its preferential distribution and greater 
uptake at the site of efficacy resulting from the higher amount of M6P on ATB200, which 
optimizes drug targeting. 
The predicted PK in humans following administration of a single 20 mg/kg IV dose of ATB200 
over a 4-hour infusion is shown in Table 3. 

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Table 3: 
Predicted PK of Single-dose Administration of ATB200 in Humans  
Parameter 
Predicted Value 
AUC0-∞ (mg·hr/L) 
1822 
Cmax (mg/L) 
423 
tmax (hr) 
4.0 
t1/2 (hr) 
2.17 
Abbreviations: AUC0-∞ = area under the plasma-drug concentration time curve from Time 0 extrapolated to infinity; 
Cmax = maximum observed plasma concentration; IV = intravenous; PK = pharmacokinetic(s); tmax = time to reach 
the maximum observed plasma concentration; t1/2 = half-life 
Note: PK was predicted for 20 mg/kg of ATB200 administered as a single IV dose over a 4-hour infusion and 
reflects active protein levels. 
The AUC0-t and Cmax values in humans based on total protein are expected to be similar to those 
based on rhGAA activity given the toxicokinetic results from the 6-month chronic toxicity study 
in NHPs. In this study, at the lowest dose tested of 30 mg/kg, similar to the anticipated 
therapeutic dose of 20 mg/kg, the AUC0-t and Cmax values for active and total protein were 
virtually identical (approximately 800 μg∙hr/mL for AUC0-t based on active and total protein and 
approximately 350 μg/mL for Cmax based on active and total protein). 
Predicted exposure in humans for single-dose administration of AT2221 is summarized in 
Table 4. 
Table 4: 
Predicted Exposure for Single-dose Administration of AT2221 in Humans 
Parameter 
AT2221 Dose  
130 mg 
260 mg 
AUC0-∞ (μg•hr/mL) 
12.35 
24.71 
Cmax (μg/mL) 
1 
2 
Abbreviations: AUC0-∞ = area under the plasma concentration time curve from Time 0 extrapolated to infinity; 
Cmax = maximum observed plasma concentration 
Source: Zavesca (miglustat): New Drug Application 21-348: Clinical Pharmacology and Biopharmaceutics 
Review(s) 2003 
6.4.2.1. 
Dose Selection for Co-administered ATB200/AT2221 
The concentration versus response relationship in Gaa KO mice (Section 6.3.1) suggested that 
co-administration of 20 mg/kg ATB200 with 10 or 20 mg/kg of AT2221 both optimizes the 
stability of ATB200 activity in plasma and maximizes glycogen reduction in quadriceps. The 
observed AT2221/ATB200 ratio of 0.01159 (ie, 10 mg/kg AT2221) is expected to correspond to 
an approximate 260 mg dose of AT2221 in a typical 70 kg human subject based on the predicted 
mean concentrations of ATB200 and AT2221 in humans (as determined from the nonclinical PK 
model described in Section 6.4.2. Targeted ratios of 0.01 and 0.02 are expected to correspond to 
AT2221 doses of 233 and 466 mg, respectively, in a typical 70 kg human subject.  
Based on an in vitro inhibition assay evaluating the inhibitory effect of AT2221 on ATB200 
activity, an approximate 260 mg dose of AT2221 is expected to bind to and stabilize ATB200 in 
plasma for up to 18 hours, and inhibition of ATB200 activity in the lysosome is only expected to 

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last approximately 4 hours. The exact timing of AT2221 administration relative to the end of 
infusion of ATB200 can be determined based on the Cmax of AT2221 of approximately 
1.5 hours. Overall, the simulations suggest that 20 mg/kg of ATB200 co-administered with 
approximately 260 mg of AT2221 is likely to produce optimal pharmacological outcomes in 
subjects with Pompe disease. 
A 14-day dosing interval is considered an adequate washout time and is greater than 5 times the 
predicted half-life for ATB200 in the circulation (2.17 hours, approximately 11 hours in total 
residence time in blood). The estimated half-life of ATB200 in lysosomes is greater than 7 to 
10 days. Additionally, the known half-life of miglustat is approximately 6 to 7 hours in plasma. 
Therefore, it would be anticipated that AT2221 would be cleared from muscle tissues to 
concentrations below pharmacologically active levels after approximately 35 hours and well 
before the end of the ATB200/AT2221 dosing interval of 14 days (Zavesca Package Insert 
2008). 
6.4.2.2. 
Predicted Safety Margins for Co-administered ATB200/AT2221 
The doses selected for the planned clinical studies are 5, 10, and 20 mg/kg ATB200 administered 
alone and 20 mg/kg ATB200 co-administered with 130 or 260 mg AT2221. Based on modeling 
and simulation, 20 mg/kg ATB200 is anticipated to result in a Cmax of 423 μg/mL and an AUC of 
1,822 μg∙hr/mL (Pharsight 2015). Assuming linear PK, an initial dose of 5 mg ATB200 is 
anticipated to result in a Cmax of approximately 100 μg/mL and an AUC of approximately 
450 μg∙hr/mL. Exposure (area under the plasma drug concentration-time curve from time zero 
extrapolated to infinite time; AUC0-∞) to AT2221 is anticipated to be approximately 
12.35 μg∙hr/mL following administration of 130 mg orally and 24.71 μg∙hr/mL following 
administration of 260 mg orally, while Cmax values are anticipated to be 1 and 2 μg/mL, 
respectively. 
Predicted safety margins in humans for co-administered ATB200/AT2221 are summarized in 
Table 5. 
Table 5: 
Predicted Safety Margins for Co-administered ATB200/AT2221 in Humans 
Parameter 
Safety Margin 
ATB200  
(5 mg/kg) 
ATB200  
(20 mg/kg) 
AT2221  
(130 mg) 
AT2221  
(260 mg) 
AUC0-t (μg∙hr/mL) 
(fold increase) 
31 to 55 
8 to 14 
20 
10 
Cmax (μg/mL)  
(fold increase) 
23 to 55 
5 to 13 
20 
10 
Abbreviations: AUC0-t = area under the concentration time curve from Time 0 to the last measurable time point, t; 
Cmax = maximum observed concentration 
Note: Predicted safety margins were based on TK data determined from long-term toxicity studies in rats and NHPs 
and a 3-month co-administration ATB200/AT2221 study in NHPs (Section 6.4.1). Data from the 3-month 
co-administration ATB200/AT2221 study in NHPs were derived from the 100 mg/kg ATB200 with 175 mg/kg 
AT2221 dose group. 

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The predicted safety margins for ATB200 administered as a single agent and co-administered 
with AT2221 support the first-in-human (FIH) clinical study using the proposed clinical doses of 
5, 10, and 20 mg/kg ATB200, and 130 and 260 mg AT2221. 
Please refer to the ATB200 Investigator’s Brochure for additional detail. 
6.4.2.3. 
PK Data from the ATB200-02 Study 
Preliminary data from ATB200-02, the current protocol regarding PK of ascending doses of 
ATB200, effect of AT2221 on the PK of ATB200 and PK of low and high dose of AT2221 are 
presented below. 
6.4.2.4. 
GAA Protein Using Signature Peptide(s) T09/T50 
Total GAA protein in plasma was measured by signature peptides T09 (primary) and T50. 
Generally, the PK of signature peptide T50 was similar to T09, and therefore confirmed the 
results of the assay. 
In Cohort 1 (ERT-experienced LOPD subjects), total GAA protein by signature peptide T09 
exposures (Cmax and AUC) demonstrated greater than dose-proportional increases during Stage 1 
(single-ascending doses of 5, 10, and 20 mg/kg ATB200). Mean AUC for the 20 mg/kg ATB200 
alone dose level was similar to translational modeling in the Gaa KO mouse to human AUC at 
the 20 mg/kg dose level (1,822 μg∙h/mL). Co-administration with 130 mg AT2221 resulted in a 
19.6% increase in total GAA protein mean AUC. Co-administration with 260 mg AT2221 
increased total GAA protein AUCs by 26.3%. These increases were mainly observed during the 
early terminal phase, as shown by observed increases in the alpha-half-life. Clearance of plasma 
total GAA protein decreased with dose escalation and remained stable when co-administered 
with AT2221.  
Generally, the PK of 20 mg/kg ATB200 based on plasma total GAA protein was similar between 
single and multiple doses when co-administered with 130 mg AT2221, and between single and 
multiple doses when co-administered with 260 mg AT2221.  
The plasma total GAA protein PK profile of Cohort 3 (ERT-naïve subjects with LOPD) was 
generally similar to Cohort 1. 
Similar to total GAA protein, in Cohort 1 (ERT-experienced LOPD subjects), total GAA activity 
exposures (Cmax and AUC) in plasma demonstrated greater than dose proportional increases 
during Stage 1 (single-ascending doses of 5, 10, and 20 mg/kg ATB200). However, 
co-administration with either the low or high dose of AT2221 did not result in any relevant 
change in total GAA activity mean AUC. Clearance of plasma total GAA activity decreased with 
dose escalation and remained stable when co-administered with AT2221. Steady-state volume of 
distribution was consistent across all treatments from approximately 4.5 to 5.9 L.  
Generally, the PK of 20 mg/kg ATB200 based on plasma total GAA activity was similar 
between single and multiple doses when co-administered with 130 mg AT2221, and between 
single and multiple doses when co-administered with 260 mg AT2221.  
The GAA activity PK profile of Cohort 3 (ERT-naïve subjects with LOPD) was generally similar 
to Cohort 1. 

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Plasma AT2221 exposures (Cmax and AUC) are approximately dose proportional. The rate of 
absorption (tmax) values support dosing with AT2221 one hour before start of ATB200 infusion, 
so that peak AT2221 concentrations are attained mid-way into infusion. Terminal elimination 
half-life was consistent at approximately 5 to 6 hours, as was plasma clearance (approximately 
10 L/h) and terminal volume of distribution (approximately 85 L). 
Overall, the preliminary exposures of ATB200 and AT2221 from approximately 10 subjects with 
LOPD are well-within the limits of the established safety margins. 
6.4.2.5. 
ATB200 Exposure Stopping Criteria 
Toxicokinetic evaluations from studies conducted in the cynomolgus monkey and rat included 
both total GAA protein concentrations and GAA activity levels in plasma. Generally, total GAA 
protein concentrations were either similar to or greater than GAA activity levels. Safety margins 
were calculated from these toxicity studies based on total protein levels as toxicity and/or 
immunotoxicity can be manifested by both active and inactive protein. Therefore, total GAA 
protein was selected to establish ATB200 exposure limits for the clinical study. Three toxicology 
studies were conducted: two 6-month dose-escalation studies with ATB200 alone to a maximum 
dose of 200 mg/kg, one in the cynomolgus monkey and one in the rat, and one 13-week 
co-administration study in the cynomolgus monkey to a maximum dose of 100 mg/kg ATB200 
co-administered with 175 mg AT2221. Exposures obtained at the highest dose levels utilized in 
these studies were NOAELs. Since the current study evaluates both ATB200 alone and 
co-administration with AT2221 (which may increase total GAA protein exposure in plasma 
relative to the same ATB200 dose alone), the 100 mg/kg ATB200 co-administered with 175 mg 
AT2221 Cmax and AUC0-t parameters were selected as the upper exposure limit for the clinical 
study. Additionally, the cynomolgus monkey is a more closely related species to humans than the 
rat and the only appropriate species to extrapolate potential effects of a biologic, such as 
ATB200, to humans. The mean Day 85 exposure at this co-administration dose level for 
ATB200 was 2,270 µg/mL (Cmax), and 13,850 µg∙hr/mL (AUC0-t). In the unlikely event a subject 
achieves one or both of these exposure levels, dosing with ATB200 alone or when 
co-administered with AT2221 will be stopped. 
6.4.2.6. 
ATB200 Preliminary Efficacy Data 
The fourth interim analysis was conducted in September 2017 with data cut-off point in 
August 2017. 
Adverse events (AEs) were generally mild and transient. Most common AEs reported as 
treatment related were nausea (3/20), tremor (3/20), headache (3/20), fatigue (3/20), diarrhea 
(2/20), muscle spasm (2/20), and joint swelling (2/20). Three incidents of infusion-associated 
reactions (IARs) in 400+ infusions which were controlled by standard premedication. One IAR 
event occurred in one nonambulatory ERT-switch patient (skin discoloration). Two IAR events 
in an ERT-naïve patient (localized pruritus, erythema and burning sensation). Longest duration 
of treatment was 72 weeks. 
Improvement in biomarkers of muscle damage (creatine phosphokinase [CK], alanine 
aminotransferase [ALT], and aspartate aminotransferase [AST]) and disease substrate (hexose 
tetrasaccharide [Hex4]) was observed for up to 58 Weeks on ATB200/AT2221 in all three 
cohorts. 

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Six-minute walk distance improved in Cohorts 1 and 3 as shown in Table 6. Qualitative and 
quantitative upper extremity muscle strength improved in Cohort 2 subjects. Forced vital 
capacity was stable in Cohort 1 and improved in Cohort 3 as shown in Table 7. 
Table 6: 
Change in 6MWT Distance in Meters in Cohorts 1 and 3 Subjects Through 
Month 18 
 
Mean (SD) 
Mean (SD) Change from Baseline 
Cohort 
Baseline  
Month 6 
Month 9 
Month 12 
Month 18 
1a 
ERT-experienced (2 to 6 years) 
(n = 10) 
397.2 
(96.8) 
(n = 10) 
+23.9 
(52.2) 
(n = 10) 
+24.5 
(40.8) 
(n = 10) 
+42.2 
(46.5) 
(n = 9) 
+51.7 
(45.9) 
3 
ERT-naïve 
(n = 5) 
399.5 
(83.5) 
(n = 5) 
+41.8 
(29.4) 
(n = 5) 
+63.5 
(23.1) 
(n = 5) 
+63.1 
(29.1) 
(n = 5) 
+49.0 
(28.3) 
Abbreviations: 6MWT = 6-minute walk test; ERT = enzyme replacement therapy; n = number of patients; 
SD = standard deviation 
a For the purposes of assigning nominal time points to data from Cohort 1, the 6-week duration of Stage 1 (single 
ascending doses of miglustat) and the 12-week duration of Stage 2 (multiple ascending doses of miglustat [130 mg 
for 6 weeks, followed by 260 mg for 6 weeks]) were included. Therefore, the Month 6, 9, 12, and 18 time points 
reflect cumulative data to Stage 3 Month 3, Stage 3 Month 6, Stage 3 Month 9, and Stage 3 Month 15, 
respectively.  
Source: Interim Analysis 6 (data cut-off date of August 2018), Table 14.2.1.3  
Table 7: 
Change in Percentage Predicted Sitting FVC (%) in Cohorts 1 and 3 Subjects 
Through Month 18 
 
Mean (SD) 
Mean (SD) Change from Baseline 
Cohort 
Baseline  
Month 6 
Month 9 
Month 12 
Month 18 
1a 
ERT-experienced (2 to 6 years) 
(n = 9) 
52.6 
(14.7) 
(n = 9) 
–1.3 
(4.1) 
(n = 9) 
–1.7 
(3.9) 
(n = 9) 
–3.3 
(6.1) 
(n = 8) 
–4.0 
(7.0) 
3 
ERT-naïve 
(n = 5) 
53.4 
(20.3) 
(n = 5) 
+4.2 
(5.6) 
(n = 5) 
+6.2 
(5.3) 
(n = 5) 
+4.4 
(8.7) 
(n = 5) 
+6.8 
(2.5) 
Abbreviations: ERT = enzyme replacement therapy; FVC = forced vital capacity; n = number of patients; 
SD = standard deviation 
a For the purposes of assigning nominal time points to data from Cohort 1, the 6-week duration of Stage 1 (single 
ascending doses of miglustat) and the 12-week duration of Stage 2 (multiple ascending doses of miglustat [130 mg 
for 6 weeks, followed by 260 mg for 6 weeks]) were included. Therefore, the Month 6, 9, 12, and 18 time points 
reflect cumulative data to Stage 3 Month 3, Stage 3 Month 6, Stage 3 Month 9, and Stage 3 Month 15, 
respectively.  
Source: Interim Analysis 6 (data cut-off date of 03 August 2018), Table 14.2.1.1  

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7. 
OBJECTIVES AND PURPOSE 
7.1. 
Primary Objectives  
• To evaluate the safety and tolerability of single-ascending doses of IV infused 
ATB200 
• To evaluate the safety and tolerability of single-ascending doses of IV infused 
ATB200 as a fixed dose, co-administered with ascending oral doses of AT2221 
• To characterize the PK of single-ascending doses of IV infused ATB200  
• To characterize the single- and multiple-dose PK of IV infused 20 mg/kg ATB200 
when co-administered with oral 130 mg or 260 mg AT2221 
• To characterize the PK of single and multiple oral doses of 130 mg or 260 mg 
AT2221 when co-administered with IV infused ATB200 
7.2. 
Secondary Objectives 
• To evaluate the long-term efficacy of 20 mg/kg of IV infused ATB200 as a fixed dose 
co-administered with oral 260 mg AT2221 in all subjects from Stage 3 
• To evaluate the long-term safety and tolerability of 20 mg/kg of IV infused ATB200 
as a fixed dose co-administered with oral 260 mg AT2221 in all subjects from Stage 3 
• To characterize single- and multiple-dose PK of plasma rhGAA activity and total 
rhGAA protein following IV infused 20 mg/kg ATB200 as a fixed dose 
co-administered with oral 260 mg AT2221 in enzyme replacement therapy 
(ERT)-naïve subjects 
• To characterize the single- and multiple-dose PK of plasma AT2221 following 
20 mg/kg of IV infused ATB200 co-administered with oral 260 mg AT2221 in 
ERT-naïve subjects 
7.3. 
Exploratory Objectives 
To evaluate:  
• Anti-rhGAA antibodies (total and neutralizing)  
• Cross-reactivity of anti-rhGAA antibodies to alglucosidase alfa  
• Pro-inflammatory cytokines and other biomarkers of immune system activation  
• PD biomarkers (urine hexose tetrasaccharide [Hex4] and serum creatine 
phosphokinase [CK]) 
• Impact of anti-rhGAA antibodies on plasma GAA total protein exposures 

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8. 
INVESTIGATIONAL PLAN 
8.1. 
Study Design  
This is an open-label, fixed-sequence, single- and multiple-ascending dose, FIH study to evaluate 
the safety, tolerability, PK, PD, and efficacy of IV ATB200 alone and when co-administered 
with oral AT2221. The study will be conducted in 4 stages.  
Stages 1 and 2: Approximately 10 to 12 ERT-experienced ambulatory subjects (Cohort 1) will be 
enrolled. In Stage 1, safety, tolerability, and PK will be evaluated following sequential 
single-ascending doses of intravenously infused ATB200 for 3 dosing periods at 5, 10, and 
20 mg/kg.  
In Stage 2, safety, tolerability, and PK will be evaluated following single- and 
multiple-ascending dose combinations: 20 mg/kg of IV ATB200 co-administered with 130 mg of 
AT2221 administered orally every 14 (± 3 days) for 3 doses, followed by 20 mg/kg of IV 
ATB200 co-administered with 260 mg of AT2221 administered orally for 3 doses, as outlined in 
Table 8. The dosing interval of 14 days, based on the current standard of care, is estimated to 
provide adequate duration for complete washout (greater than 5 half-lives) of ATB200 (predicted 
half-life of 2.17 hours) and AT2221 (half-life of 6 to 7 hours). Cohort 1 subjects who have 
completed Stages 1 and 2 will enter into a long-term extension stage of the study, hereinafter 
referred to as Stage 3, and will continue to be assessed for safety, tolerability, and efficacy of 
long-term co-administration of ATB200 and AT2221. In addition, functional assessments 
relevant to Pompe disease will be performed at regular intervals per the Schedule of Assessments 
(Table 9, Table 10, Table 11, Table 12, and Table 13). 
Stage 3: Approximately 12 to 18 additional subjects will enroll, approximately 4 to 6 of whom 
will be ERT-experienced nonambulatory subjects (Cohort 2), approximately 5 of whom will be 
ERT-naïve ambulatory subjects (Cohort 3) and approximately 6 to 8 of whom will be ambulatory 
subjects with ERT experience of at least 7 years (Cohort 4). Single- and multiple-dose serial PK 
sampling will be conducted for Cohort 3 subjects but not for Cohort 2 or 4 subjects. Many 
nonambulatory subjects lack contralateral venous access as a result of sclerosis within peripheral 
veins. In addition, the intensive PK sampling in this study is likely to present an undue burden to 
nonambulatory subjects. For these reasons, no PK assessments will be conducted in 
nonambulatory subjects. PK analysis will not be conducted for Cohort 4 due to the similarity of 
patient populations in Cohorts 1 and 4, and the well-characterized PK in Cohort 1. Stage 3 will 
continue for a period of two years for Cohorts 1, 3 and 4.  
Stage 4: Subjects who complete Stage 3 will enter into Stage 4. Stage 4 treatment period will be 
continued as open-label extension and will continue until the date of regulatory approval or 
marketing authorization and/or commercialization in the participating subject’s country, or study 
termination by the sponsor, Amicus Therapeutics, Inc. (Amicus). 
In all stages, every effort should be made to maintain the duration of infusion of ATB200 at 
4-hours (± 15 min). Changes in the duration of ATB200 infusion due to safety or tolerability 
issues will be documented. 

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In this study, ERT-experienced ambulatory subjects are defined as adults with Pompe disease 
who have been on ERT for 2 to 6 years (Cohort 1) and ≥ 7 years (Cohort 4) prior to enrollment 
and who are able to walk at least 200 meters in the 6MWT. 
ERT-experienced nonambulatory subjects (Cohort 2), are defined as adults with Pompe disease 
who are wheelchair bound and unable to walk unassisted, have been on ERT (alglucosidase alfa) 
for ≥ 2 years prior to enrollment.  
ERT-naïve ambulatory subjects (Cohort 3), are defined as adults with Pompe disease who have 
never received treatment with ERT for Pompe disease and who are able to walk at least 
200 meters in the 6MWT. 
If a subject prematurely withdraws from the study, the subject may be replaced with a subject 
who qualifies for any cohort. If any of the sentinel subjects withdraw prematurely from the 
study, that subject will be replaced by the next subject enrolled in that cohort (eg, if Subject 1 
withdraws, Subject 3 will replace that subject as a sentinel subject). 
The study is composed of a Screening Visit, a Baseline Visit, Stage 1 (3-period, fixed-sequence, 
single-ascending dose PK study of ATB200 alone), Stage 2 (2-period, fixed-sequence, 
single- and multiple-dose PK study of 20 mg/kg ATB200 co-administered with 
multiple-ascending doses of AT2221), and Stage 3 and Stage 4 treatment period will be 
continued as open-label extension and will continue until the date of regulatory approval or 
marketing authorization and/or commercialization in the participating subject’s country, or study 
termination by Amicus. Additional serial 24-hour PK visits are included in Stage 3 for subjects 
in Cohort 3. If a subject is withdrawing from the study, they will return for an Early Termination 
(ET) visit within 30 days of their last visit. 
The assessments to be performed at each study visit are described in Table 9 for all subjects in 
Stages 1 and 2, and Table 10, Table 11, Table 12, and Table 13 for all subjects in Stage 3 and 4. 
8.2. 
Safety Monitoring and Sentinel Dosing 
Safety will be monitored by the Amicus Medical Monitor and the investigators on a continuous 
basis and on a regular basis by a Safety Steering Committee (SSC). The details of the 
membership, meeting schedules, procedures, roles, and responsibilities of the SSC are detailed in 
the SSC Charter.  
Study treatment may be interrupted or permanently stopped by the Amicus Medical Monitor and 
the SSC, if warranted by the safety and tolerability data. Subjects will be monitored in a hospital 
or infusion center for 48 hours from the start of each infusion during Stage 1 (ie, ERT 
dose-escalation stage). Since the target infusion duration in the study is 4 hours, all subjects will 
be closely monitored for the first 4 hours during their infusion and then observed in hospital for 
an additional 44 hours prior to discharge. Subjects will be admitted and dosed at either an 
infusion center or a hospital and thereafter hospitalized for the remainder of the observation 
period.  
In Stages 2 and 3, all subjects will be monitored at a hospital or infusion center for an additional 
2 to 4 hours from the end of their infusion. Once a subject has completed one year in Stage 3, the 
subjects, who have not experienced IARs for prior 6 months, can be monitored for one hour post 
infusion at the PI’s discretion. Subjects who switch to home infusion, must be monitored for 2 to 

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4 hours for a period of at least 3 months. If no IARs occur, the monitoring can be reduced to one 
hour post infusion at the PIs discretion. Refer to Section 11.1.3 for further information on IARs, 
including their reporting and management. 
When at least one of the 2 Cohort 1 sentinel subjects has completed Period 5 dosing, and the 
safety data has been reviewed by the SSC, subjects from Cohorts 2 and 3 can begin enrollment 
into Stage 3. The first 2 subjects from Cohorts 2 and 3 will undergo sentinel dosing in the same 
manner as subjects from Cohort 1 during Stage 2. 
Sentinel Dosing 
The first 2 subjects in Cohort 1 of this study will be the sentinel subjects for the study and will be 
the first 2 subjects dosed in each period of the study (Periods 1 to 5). The first 2 subjects dosed in 
each cohort will be the sentinel subjects for that cohort. In the event that a sentinel subject is 
prematurely withdrawn from the study, he/she will be replaced by another subject. 
Note: At least one of the 2 sentinel subjects will complete Period 5, Stage 2 dosing, and the 
safety data will be reviewed by the SSC, before any newly enrolled subjects in Cohorts 2 
and 3 can be dosed. The first 2 subjects in Cohorts 2 and 3 will also serve as sentinel subjects for 
their respective cohorts. 
In Stage 1 (Periods 1, 2, and 3), subjects will be dosed with single-ascending doses of ATB200 
(5 mg/kg [Period 1], 10 mg/kg [Period 2], and 20 mg/kg [Period 3]). 
Following the dosing of the 2 sentinel subjects for each study period in Stage 1, an evaluation of 
the available safety data (physical examination [PE], vital signs, adverse events [AEs], infusion 
reactions, electrocardiogram [ECG], and available locally performed laboratory tests) will be 
performed within 24 to 48 hours by the Amicus Medical Monitor and the investigators. The SSC 
will convene for a formal safety review when central safety laboratory data are available for both 
sentinel subjects at each dose level. If the SSC determines that there are no safety concerns that 
preclude dosing at the dose assigned for that period, 10 additional subjects will be enrolled and 
dosed. 
Note: Vital signs will be monitored as detailed in Table 9, Table 10, Table 11, Table 12, and 
Table 13. For PK Visits 3, 4, 5, 6, and 9, vital signs will be monitored at hours 0, 1, 4, 6, 12, and 
24 after the start of infusion. During the 48-hour observation period, vital signs will be 
monitored, at a minimum, every 6 to 8 hours until the end of the 48-hour observation period. 
The SSC will also convene for a safety review when safety data (including central laboratory 
safety data) for all subjects at all three Stage 1 dose levels are available.  
In Stage 2 (after Visits 6 and 9), safety data from the 2 sentinel subjects will be reviewed by the 
SSC, and safety will be assessed after the first dose as for each period in Stage 1. If the SSC 
determines that there are no safety concerns that preclude additional dosing at 20 mg/kg ATB200 
co-administered with 130 mg AT2221 (Visit 6) or 20 mg/kg ATB200 co-administered with 
260 mg AT2221 (Visit 9), the remaining subjects in Cohort 1 will receive Stage 2 treatment. 
Stage 3 sentinel dosing will be performed for the first 2 subjects in Cohort 2 and the first 
2 subjects in Cohort 3. If the SSC determines that there are no safety concerns that preclude the 
additional dosing of 20 mg/kg of ATB200 co-administered with 260 mg of AT2221, the 
remaining 2 to 4 additional subjects in Cohort 2 and the remaining 2 to 4 additional subjects in 
Cohort 3 will also be dosed.  

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Subjects from Cohorts 2 and 3 will not begin dosing until at least one of the 2 sentinel subjects in 
Cohort 1 have completed Period 5, Stage 2 dosing and the review of safety data has been 
completed by the SSC.  
The SSC will reconvene when all safety data (including central safety laboratory data) are 
available for all subjects at the end of Stage 2. 
The SSC will also convene ad hoc in case of a Suspected Unexpected Serious Adverse Reaction 
(SUSAR) or an identified safety concern.  
The SSC may recommend any of the following review: 
• Continue the study without modifications 
• Continue the study with modifications (amendment) 
• Temporarily halt dosing 
• Permanently stop dosing 
If in the opinion of the SSC there are no AEs or safety concerns in the sentinel subjects that 
might preclude continued study dosing, dosing will continue for all remaining subjects at that 
dose level.  
Subject safety will continue to be closely monitored by the Amicus Medical Monitor and study 
investigators on an ongoing basis, and at regular intervals by the SSC.  
8.3. 
Pharmacokinetic Sampling Details  
The PK assessments in this study include blood sampling for plasma GAA activity levels, 
plasma total GAA protein concentrations, and plasma AT2221 concentrations. 
PK assessments will be performed as described in Table 9, Table 12, Table 14, and Table 15.  

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Figure 1: 
Study Design Schematic 
  
 
Abbreviations: GAA = acid α-glucosidase; PK = pharmacokinetics; QOW = every other week 
a PK assessments for GAA activity, total GAA protein and AT2221 in Stage 3 will only be performed for the first 
and third doses for Cohort 3. Sparse blood sampling for total GAA protein will be performed after at least 18 months 
of treatment in Cohorts 1 and 3. If the subject has completed Stage 3, sparse PK sampling will be performed in 
Stage 4. 
8.4. 
Details of Study Treatment 
Cohort 1 subjects will be administered ATB200 as a single agent and ATB200 co-administered 
with AT2221 according to the treatment assignment in Table 8. Cohorts 2, 3, and 4 will only 
receive ATB200 co-administered with AT2221 according to the treatment assignment in Table 8. 
Table 8: 
Treatment Assignment for Stages 1, 2, 3, and 4 
Cohorts 
Stage 1 
(6 weeks) 
Stage 2 
(12 weeks) 
Stage 3 
(2 years) 
Stage 4 
(Until Approval) 
Period 
1 
Single-
Dose 
Period 
2 
Single-
Dose 
Period 
3 
Single-
Dose 
Period 4 
3 Multiple 
Doses 
Co-
administration 
Period 5 
3 Multiple 
Doses  
Co-
administration 
Multiple Dose, 
24 months, 
Extension 
Co-
administration 
Multiple Dose, 
Long-term, 
Extension 
Co-
administration 
Cohort 
1 
(n = 11) 
5 mg/kg 
ATB200 
10 mg/kg 
ATB200 
20 mg/kg 
ATB200 
20 mg/kg 
ATB200 + 
130 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Cohort 
2 
(n = 4-6) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 

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Table 8: 
Treatment Assignment for Stages 1, 2, 3, and 4 (Continued) 
Cohorts 
Stage 1 
(6 weeks) 
Stage 2 
(12 weeks) 
Stage 3 
(2 years) 
Stage 4 
(Until Approval) 
Period 
1 
Single-
Dose 
Period 
2 
Single-
Dose 
Period 
3 
Single-
Dose 
Period 4 
3 Multiple 
Doses 
Co-
administration 
Period 5 
3 Multiple 
Doses  
Co-
administration 
Multiple Dose, 
24 months, 
Extension 
Co-
administration 
Multiple Dose, 
Long-term, 
Extension 
Co-
administration 
Cohort 
3 
(n = 5) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Cohort 
4 
(n = 6-8) 
NA 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
20 mg/kg 
ATB200 + 
260 mg 
AT2221 
Abbreviations: NA = not applicable; SSC = Safety Steering Committee  
Note: At least one of the 2 sentinel subjects will complete Period 5, Stage 2 dosing, and the safety data will be 
reviewed by the SSC, before any newly enrolled subjects in Cohorts 2 and 3 can be dosed. The first 2 subjects in 
Cohorts 2 and 3 will also serve as sentinel subjects for their respective cohorts. 
8.5. 
Stopping Criteria 
Subjects may be discontinued from study medication and withdrawn from the study if they meet 
any of the following stopping criteria: 
• Any moderate or severe AE that is at least probably related to study treatment and 
that poses a significant safety risk to the subject, in the opinion of any one of the 
following: the principal investigator, Amicus Medical Monitor, or SSC 
• A serious adverse event (SAE) that is deemed by the investigator or Amicus Medical 
Monitor to be at least probably related to study treatment 
• Intolerable AE, in the opinion of the investigator 
Subjects must discontinue study medication and be withdrawn from the study if they meet any of 
the following stopping criteria: 
• Anaphylactic reaction to study treatment, as defined by the Sampson Criteria 
(Appendix 1) 
• SSC decision based on safety data review 
• Any of the following abnormal liver function tests in the absence of a reason other 
than study treatment, to explain the abnormalities 
− Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 8 × upper 
limit of normal (ULN) 
− ALT or AST > 5 × ULN for more than 2 weeks 
− ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN) 

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− ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%) 
• Pregnancy 
Adverse events that meet the stopping criteria and are reported as serious or severe (per the 
intensity scale used in Section 11.3), will also be graded using the version of the Common 
Terminology Criteria for Adverse Events (CTCAE) that is current at study initiation. 
Adverse events that meet the stopping criteria will be considered stopping events if they are: 
• Deemed related to study treatment  
• Classified as Grade ≥ 3 based on the current version of the CTCAE  
• In any of the following System Organ Classes: 
− Hepatobiliary Disorders 
− Injury, Poisoning and Procedural Complications 
− Blood and Lymphatic System Disorders 
− Cardiac Disorders 
− Renal and Urinary Disorders 
− Nervous System Disorders 
8.6. 
Concomitant Medications and Nondrug Therapies 
Concomitant medications taken within 4 weeks prior to the Screening Visit or at any time 
throughout the study must be recorded in the electronic case report forms (eCRFs).  
Concomitant medications and nondrug therapies (eg, procedures, surgery, physical therapy, 
assistive devices, etc) specifically associated with an AE or IAR should be entered into the 
corresponding eCRFs. 
8.7. 
Prohibited Medications  
All prohibited medications must be discontinued at least 30 days before the Baseline Visit.  
Use of the following medications by all subjects is prohibited during this study:  
• miglitol (eg, Glyset) 
• non-study miglustat (eg, Zavesca) 
• Myozyme®/Lumizyme® after treatment with ATB200 has begun 
• acarbose (eg, Precose, Glucobay) 
• voglibose (eg, Volix®, Vocarb®, and Volibo®) 
Note: None of these medications have a half-life that, when multiplied by 5, is longer 
than 30 days. 

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• oral β2-receptor agonists and non-selective β-blockers (eg, propranolol, nadalol and 
carvedilol). In situations in which the subject has been on a stable dose of a 
non-selective β-blocker or has a medical need to be started on that medication, and it 
is deemed the most appropriate medication for the subject by the PI or by the primary 
treating physician, subject may be treated with that medication. This decision will be 
made by the PI in discussion with Amicus Medical Monitor. 
• any investigational/experimental drug 
8.8. 
Criteria for Termination of the Study 
The study may be terminated by the sponsor for any of the following reasons: 
• evidence suggesting that safety risks associated with ATB200/AT2221 treatment 
outweigh the potential benefits or at the recommendation of the Safety Steering 
Committee (SSC) (Section 14.3) 
• lack of efficacy 
• inability to enroll the targeted number of subjects  

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9. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1. 
Number of Subjects 
Approximately 18 to 34 subjects will enroll in the study. Approximately 10 to 12 subjects, are 
planned to be enrolled in Cohort 1 of this study, and these subjects will participate in Stage 1 
and 2. Stage 3 of the study will continue to treat subjects from Cohort 1 and will also enroll 
another 12 to 18 subjects approximately; 4 to 6 subjects from Cohort 2; 5 subjects from 
Cohort 3; and approximately 6 to 8 from Cohort 4.  
Subjects who withdraw prematurely from this study may be replaced by subjects eligible for any 
cohort. If one of the 2 sentinel subjects withdraws prematurely from the study, that subject will 
be replaced by the next subject enrolled in the study (eg, if Subject 1 withdraws, Subject 3 will 
replace that subject as a sentinel subject). 
9.2. 
Eligibility Criteria 
During the Screening Visits, subjects with Pompe disease will be evaluated against the eligibility 
criteria given below, as appropriate. Separate sets of criteria exist for ERT-experienced or 
ERT-naïve ambulatory subjects and ERT-experienced nonambulatory subjects. Each subject 
must meet all of the inclusion criteria and none of the exclusion criteria. Waivers of 
inclusion/exclusion criteria are not permitted. Subjects who initially screen fail may be 
rescreened. 
9.2.1. 
Inclusion and Exclusion Criteria 
Cohort 1 
Inclusion Criteria 
1. Male and female subjects between 18 and 65 years of age, inclusive 
2. Subject must provide signed informed consent prior to any study-related procedures 
3. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
4. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
5. Subject has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for the previous 
2 to 6 years, inclusive  
6. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme) at a frequency of 
once every other week 
7. Subject has received and completed the last 2 infusions without a drug-related adverse 
event resulting in dose interruption 
8. Subject must be able to walk between 200 and 500 meters on the 6MWT 
9. Upright FVC must be 30% to 80% of predicted normal value 

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Exclusion Criteria 
1. Subject has received any investigational therapy including adjunctive therapy for Pompe 
disease, other than alglucosidase alfa within 30 days or 5 half-lives of the therapy or 
treatment, whichever is longer, prior to the Baseline Visit, or anticipates doing so during 
the study 
2. Subject has received treatment with prohibited medications (see Section 8.7) within 
30 days of the Baseline Visit 
3. Subject, if female, is pregnant or breastfeeding at screening 
4. Subject, whether male or female, is planning to conceive a child during the study 
5. Subject requires invasive ventilatory support  
6. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
7. Subject has a medical or any other extenuating condition or circumstance that may, in the 
opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
8. Subject has a history of anaphylaxis to alglucosidase alfa 
9. Subject has a history of high sustained anti-rhGAA antibodies (see Section 10.4)  
10. Subject has a history of allergy or sensitivity to miglustat or other iminosugars  
11. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor  
12. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Cohort 2 
Inclusion Criteria 
10. Male and female subjects between 18 and 65 years of age, inclusive 
11. Subject must provide signed informed consent prior to any study-related procedures 
12. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
13. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
14. Subject has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for ≥ 2 years 
15. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme) at a regular or set 
frequency 
16. Subject has received and completed the last 2 infusions without a drug-related adverse 
event resulting in dose interruption 

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17. Subject must be wheelchair-bound and unable to walk unassisted 
Exclusion Criteria 
13. Subject has received any investigational therapy including adjunctive therapy for Pompe 
disease, other than alglucosidase alfa within 30 days or 5 half-lives of the therapy or 
treatment, whichever is longer, prior to the Baseline Visit, or anticipates to do so during 
the study 
14. Subject has received treatment with prohibited medications (see Section 8.7) within 
30 days of the Baseline Visit  
15. Subject, if female, is pregnant or breastfeeding at screening 
16. Subject, whether male or female, is planning to conceive a child during the study 
17. Subject has a medical or any other extenuating condition or circumstance that may, in the 
opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
18. Subject has a history of anaphylaxis to alglucosidase alfa 
19. Subject has a history of high sustained anti-rhGAA antibodies (see Section 10.4) 
20. Subject has a history of allergy or sensitivity to miglustat or other iminosugars 
21. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor 
22. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Cohort 3 
Inclusion Criteria 
18. Male and female subjects between 18 and 65 years of age, inclusive 
19. Subject must provide signed informed consent prior to any study-related procedures 
20. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
21. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
22. Subject must be able to walk between 200 to 500 meters on the 6MWT 
23. Upright FVC must be 30% to 80% of predicted normal value 
Exclusion Criteria 
23. Subject has received any ERT, including alglucosidase alfa at any time, or any 
investigational therapy for Pompe disease within 30 days or 5 half-lives of the therapy or 
treatment, whichever is longer, prior to the Baseline Visit, or anticipates doing so during 
the study 

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24. Subject has received treatment with prohibited medications (see Section 8.7) within 
30 days of the Baseline Visit 
25. Subject, if female, is pregnant or breastfeeding at screening 
26. Subject, whether male or female, is planning to conceive a child during the study 
27. Subject requires invasive ventilatory support 
28. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
29. Subject has a medical or any other extenuating condition or circumstance that may, in the 
opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
30. Subject has a history of allergy or sensitivity to miglustat or other iminosugars 
31. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor 
32. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
Cohort 4 
Inclusion Criteria 
24. Male and female subjects between 18 and 75 years of age, inclusive 
25. Subject must provide signed informed consent prior to any study-related procedures 
26. Subject has documented 6MWT on three separate occasions, each at least six months 
apart with at least two values in the past three years 
27. Subjects of childbearing potential must agree to use medically accepted methods of 
contraception during the study and for 90 days after last co-administration of ATB200 
and AT2221 
28. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA 
enzyme activity or by GAA genotyping 
29. Subject has received ERT for the previous ≥ 7 years 
30. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme) at a frequency of 
once every other week 
31. Subject has received and completed the last 2 infusions without a drug-related AE 
resulting in dose interruption 
32. Subject must be able to walk between 75 and 600 meters on the 6MWT 
33. Upright FVC must be 30% to 85% of predicted normal value 
Exclusion Criteria 
33. Subject has received any investigational therapy including adjunctive therapy for Pompe 
disease, other than alglucosidase alfa within 30 days, or 5 half-lives of the therapy or 

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treatment, whichever is longer, prior to the Baseline Visit, or anticipates doing so during 
the study 
34. Subject has received treatment with prohibited medications (see Section 8.7) within 
30 days of the Baseline Visit 
35. Subject, if female, is pregnant or breastfeeding at screening 
36. Subject, whether male or female, is planning to conceive a child during the study 
37. Subject requires invasive ventilatory support  
38. Subject uses noninvasive ventilatory support ≥ 6 hours a day while awake 
39. Subject has a medical or any other extenuating condition or circumstance that may, in the 
opinion of the investigator or the Medical Monitor, pose an undue safety risk to the 
subject or compromise his/her ability to comply with protocol requirements 
40. Subject has a history of anaphylaxis to alglucosidase alfa 
41. Subject has a history of high sustained anti-rhGAA antibodies (see Section 10.4) 
42. Subject has a history of allergy or sensitivity to miglustat or other iminosugars  
43. Subjects with active systemic autoimmune disease such as lupus, scleroderma, or 
rheumatoid arthritis; all subjects with autoimmune disease must be discussed with the 
Amicus Medical Monitor  
44. Subjects with active bronchial asthma; all subjects with bronchial asthma must be 
discussed with the Amicus Medical Monitor 
9.3. 
Withdrawal Criteria 
Subjects may discontinue study treatment, withdraw from the study, or be withdrawn from the 
study for any reason including, but not limited to, the following:  
• at their own request or at the request of their legally authorized representative∗ 
• if, in the investigator’s opinion, continuation in the study would be detrimental to the 
subject’s well-being 
• occurrence of an intolerable treatment-emergent adverse event (TEAE) as determined 
by the investigator and/or the subject  
• failure of the subject to return to the study site for scheduled visits 
• persistent noncompliance 
• sponsor decision to terminate the study 
                                                 
∗“Legally authorized representative” means an individual or judicial or other body authorized under applicable law 
to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the 
research. 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
Page 66 of 158 
Pregnancy 
Any subject who becomes pregnant during the study must be withdrawn from study treatment 
and will be followed through the outcome of the pregnancy.  
In all cases, the reason for and date of withdrawal must be recorded in the eCRF and in the 
subject’s medical records. The subject must be followed up to establish whether the reason was 
an AE and, if so, the AE must be reported as described in Section 11.4. All subjects who 
discontinue study treatment will be encouraged to return for an ET Visit. 
In case the subject wishes to discontinue treatment, the investigator must inquire and document 
in the medical record whether:  
• the subject only wants to discontinue study treatment but agrees to the follow-up 
procedures as outlined in the protocol  
• the subject wants to discontinue study treatment and all follow-up procedures  
• the subject wants to revoke the consent to collect and use further data  
Note: In the US, the authorization to use and disclose data for research can only be revoked in 
writing by the subject.  
The investigator must make every effort to contact subjects who discontinue study treatment or 
visits or are lost to follow-up and schedule the ET assessments. Attempts to contact subjects who 
are lost to follow-up (eg, times and dates of attempted telephone contact, receipt for sending a 
registered letter) must be documented in the subject’s source document. 
9.4. 
Replacement of Subjects 
Subjects who withdraw or are withdrawn from the study may be replaced. If one of the 2 sentinel 
subjects withdraws prematurely from the study, that subject will be replaced by the next subject 
enrolled in the study (eg, if Subject 1 withdraws, Subject 3 will replace that subject as a sentinel 
subject). 
Replacement of a subject may only occur after consultation with, and written approval of, the 
Amicus Medical Monitor. 
9.5. 
Subjects of Reproductive Potential 
The allowed methods of contraception described in the following text are only effective when 
used consistently, correctly, and in accordance with the product label. 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. 
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. 
Woman of childbearing potential: defined as all women physiologically capable of becoming 
pregnant, must use highly effective contraception during the study and through 90 days after the 
study treatment. Highly effective contraception is defined as either: 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
Page 67 of 158 
• Total abstinence: When this is in line with the preferred and usual lifestyle of the 
subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
• Sterilization: Subject has had surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least 6 weeks before taking study treatment. In case 
of oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow up hormone level assessment and she is not of childbearing 
potential. 
• Male partner sterilization (with the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate). For female study subjects, male partner(s) must 
have undergone sterilization. 
• Use a combination of 2 of the following (eg, both a+b) (all countries, with the 
exception of the UK):  
a. placement of a nonhormonal intrauterine device or nonhormonal intrauterine 
system 
b. barrier method of contraception: condom or occlusive cap (diaphragm or cervical 
vault caps) with spermicidal foam/gel/film/cream/vaginal suppository (not 
applicable in Australia) 
c. hormonal contraception methods (eg, oral, injected, implanted) 
• Use of a combination of the placement of a nonhormonal intrauterine device/system 
and a hormonal contraception method (eg, oral, injected, implanted) (UK only) 
Note: Women are considered post-menopausal and not of childbearing 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 
serum FSH levels > 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 childbearing potential. 
Male subjects and their partners must use highly effective methods of contraception (double 
barrier, eg, spermicidal gel plus condom [all countries, except the UK]) 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 treatment 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 11.6.1. 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
Page 68 of 158 
10. 
STUDY ASSESSMENTS AND PROCEDURES  
The schedule of assessments and procedures display each study assessment and procedure along 
with the scheduled time of occurrence and can be found in Table 9 for subjects from Cohort 1 
through the end of Stage 2, Table 10 for subjects from Cohort 1 who continue to Stage 3 and 4, 
Table 11 for subjects from Cohort 2 who begin treatment in Stage 3, Table 12 for subjects from 
Cohort 3 who begin treatment in Stage 3, and Table 13 for subjects from Cohort 4 who begin 
treatment in Stage 3. Serial blood sampling time points for PK and immunological assessments 
are provided in Table 14. Sparse blood sampling time points for plasma total GAA protein for 
subjects from Cohorts 1 and 3 in Stage 3 are provided in Table 15. 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. 
Assessments that occur throughout the study, where applicable and to the extent possible, should 
be completed during the designated visit, preferably in the order specified in the study procedure 
manual. Once established, every effort should be made to maintain the order of procedures at 
each study visit throughout the study.  

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 69 of 158 
Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects 
Assessments or 
Proceduresa 
Screening 
Baseline 
Stage 1b 
Stage 2b 
Stage 3  
Period 1 
Period 2 
Period 3  
Period 4 
Period 5 
End of PK  
Visit 1 
Days -28 
to -1 
Visit 2 
Day 0 
Visit 3 
Day 1 
(±3 d) 
Visit 4 
Day 15 
(±3 d) 
Visit 5 
Day 29 
(±3 d) 
Visit 6 
Day 43 
(±3 d) 
Visit 7 
Day 57 
(±3 d) 
Visit 8 
Day 71 
(±3 d) 
Visit 9 
Day 85 
(±3 d) 
Visit 10 
Day 99 
(±3 d) 
Visit 11 
Day 113 
(±3 d) 
Visit 12 
Day 127 
(±3 d) 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
Assign subject 
number 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
IXRS 
Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history, 
fall history, and 
prior medications 
X 
X 
 
 
 
 
 
 
 
 
 
 
AEs, SAEs, 
IARs, and falls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nondrug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs
c, d  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examinatione 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study ATB200-02 Amendment 08 
 
Page 70 of 158 
Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Screening 
Baseline 
Stage 1b 
Stage 2b 
Stage 3  
Period 1 
Period 2 
Period 3  
Period 4 
Period 5 
End of PK  
Visit 1 
Days -28 
to -1 
Visit 2 
Day 0 
Visit 3 
Day 1 
(±3 d) 
Visit 4 
Day 15 
(±3 d) 
Visit 5 
Day 29 
(±3 d) 
Visit 6 
Day 43 
(±3 d) 
Visit 7 
Day 57 
(±3 d) 
Visit 8 
Day 71 
(±3 d) 
Visit 9 
Day 85 
(±3 d) 
Visit 10 
Day 99 
(±3 d) 
Visit 11 
Day 113 
(±3 d) 
Visit 12 
Day 127 
(±3 d) 
Patient-reported Outcomes 
R-PAct scale 
 
X 
 
 
 
 
 
 
 
 
 
X 
RHS 
 
X 
 
 
 
 
 
 
 
 
 
X 
FSS 
 
X 
 
 
 
 
 
 
 
 
 
X 
PROMIS® 
measurements for 
dyspnea, fatigue, 
physical 
functioning, and 
upper extremityf 
 
X 
 
 
 
 
 
 
 
 
 
X 
Clinical Safety Laboratory Assessments, Immunological Assessments, and Urine Collections 
Serum chemistry 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
anti-rhGAA 
antibodies
g 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
assessments of 
neutralizing 
antibodiesg 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study ATB200-02 Amendment 08 
 
Page 71 of 158 
Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Screening 
Baseline 
Stage 1b 
Stage 2b 
Stage 3  
Period 1 
Period 2 
Period 3  
Period 4 
Period 5 
End of PK  
Visit 1 
Days -28 
to -1 
Visit 2 
Day 0 
Visit 3 
Day 1 
(±3 d) 
Visit 4 
Day 15 
(±3 d) 
Visit 5 
Day 29 
(±3 d) 
Visit 6 
Day 43 
(±3 d) 
Visit 7 
Day 57 
(±3 d) 
Visit 8 
Day 71 
(±3 d) 
Visit 9 
Day 85 
(±3 d) 
Visit 10 
Day 99 
(±3 d) 
Visit 11 
Day 113 
(±3 d) 
Visit 12 
Day 127 
(±3 d) 
Blood sample for 
measurement of 
pro-inflammatory 
cytokines and/or 
other biomarkers 
of immune 
system 
activationh 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
exploratory 
biomarkers of 
Pompe disease 
and 
immunogenicityg 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IgE  
measurementi 
X 
If needed 
Confirm Pompe 
diagnosis: blood 
sample for GAA 
genotyping if 
needed 
X 
 
 
 
 
 
 
 
 
 
 
 
PK Assessments (also see Table 14 for times of blood sampling)j 
Serial blood 
samples for 
plasma GAA 
activityk 
 
 
X 
X 
X 
X 
X
l 
X 
X 
X
l 
X 
 

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Study ATB200-02 Amendment 08 
 
Page 72 of 158 
Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Screening 
Baseline 
Stage 1b 
Stage 2b 
Stage 3  
Period 1 
Period 2 
Period 3  
Period 4 
Period 5 
End of PK  
Visit 1 
Days -28 
to -1 
Visit 2 
Day 0 
Visit 3 
Day 1 
(±3 d) 
Visit 4 
Day 15 
(±3 d) 
Visit 5 
Day 29 
(±3 d) 
Visit 6 
Day 43 
(±3 d) 
Visit 7 
Day 57 
(±3 d) 
Visit 8 
Day 71 
(±3 d) 
Visit 9 
Day 85 
(±3 d) 
Visit 10 
Day 99 
(±3 d) 
Visit 11 
Day 113 
(±3 d) 
Visit 12 
Day 127 
(±3 d) 
Serial blood 
samples for 
plasma total 
GAA protein 
concentrationk 
 
 
X 
X 
X 
X 
X
l 
X 
X 
X
l 
X 
 
Serial blood 
samples for 
plasma AT2221 
concentrationm 
 
 
 
 
 
X 
X
l 
X 
X 
X
l 
X 
 
Miscellaneous Tests 
Collect aliquot of 
infusion solutionn 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancyo 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine sample for 
Hex4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary Function Tests 
SNIP 
 
X 
 
 
 
 
 
 
 
 
 
X 
MIP 
 
X 
 
 
 
 
 
 
 
 
 
X 
MEP 
 
X 
 
 
 
 
 
 
 
 
 
X 
FVC 
 
X 
 
 
 
 
 
 
 
 
 
X 

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Study ATB200-02 Amendment 08 
 
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Table 9: 
Schedule of Assessments for Stages 1 and 2, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Screening 
Baseline 
Stage 1b 
Stage 2b 
Stage 3  
Period 1 
Period 2 
Period 3  
Period 4 
Period 5 
End of PK  
Visit 1 
Days -28 
to -1 
Visit 2 
Day 0 
Visit 3 
Day 1 
(±3 d) 
Visit 4 
Day 15 
(±3 d) 
Visit 5 
Day 29 
(±3 d) 
Visit 6 
Day 43 
(±3 d) 
Visit 7 
Day 57 
(±3 d) 
Visit 8 
Day 71 
(±3 d) 
Visit 9 
Day 85 
(±3 d) 
Visit 10 
Day 99 
(±3 d) 
Visit 11 
Day 113 
(±3 d) 
Visit 12 
Day 127 
(±3 d) 
Motor Function Tests
p 
Gower’s 
maneuver 
 
X 
 
 
 
 
 
 
 
 
 
X 
TUG 
 
X 
 
 
 
 
 
 
 
 
 
X 
10MWT 
 
X 
 
 
 
 
 
 
 
 
 
X 
4-stair climb 
 
X 
 
 
 
 
 
 
 
 
 
X 
GSGC score 
 
X 
 
 
 
 
 
 
 
 
 
X 
6MWT 
 
X 
 
 
 
 
 
 
 
 
 
X 
Muscle Strength Tests 
Manual muscle 
strength by MRC 
 
X 
 
 
 
 
 
 
 
 
 
X 
Quantitative 
muscle strength 
by hand-held 
dynamometer 
 
X 
 
 
 
 
 
 
 
 
 
X 
Study Dosing 
AT2221 (mg) 
 
 
N/A 
N/A 
N/A 
130 
130 
130 
260 
260 
260 
260
q 
ATB200 (mg/kg) 
 
 
5 
10 
20 
20 
20 
20 
20 
20 
20 
20
q 
Abbreviations: 6MWT = 6-Minute Walk Test; 10MWT = 10-Meter Walk Test; AE = adverse event; anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; 
ECG = electrocardiogram; ET = Early Termination (visit); FSS = Fatigue Severity Scale; FVC = forced vital capacity; GAA = human acid α-glucosidase; GAA = gene that encodes 
human acid α-glucosidase (GAA protein); GSGC = gait, stairs, Gower, chair maneuver; Hex4 = hexose tetrasaccharide; IAR = infusion-associated reaction; 
IgE = immunoglobulin E; IXRS = interactive response technology trial management system; MRC = medical research criteria; MEP = maximum expiratory pressure; 
MIP = maximum inspiratory pressure; N/A = not applicable; PK = pharmacokinetics; PROMIS = Patient-reported Outcomes Measurement Information System; 

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Study ATB200-02 Amendment 08 
 
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rhGAA = recombinant human acid α-glucosidase; RHS = Rotterdam Handicap Scale; R-PAct = Rasch-built Pompe-specific activity; SAE = serious adverse event; SNIP = Sniff 
Nasal Inspiratory Pressure; TUG = Timed Up and Go 
a All study assessments will be performed on the day indicated for each period. Twenty-four-hour PK assessments will take place on the second day of each visit (see Table 14). 
b Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be followed by safety review by investigators and Amicus Medical Monitor before dosing 
all the other subjects. 
c Sitting vital sign assessments will include measurement of body temperature, rate of respiration, heart rate, and systolic and diastolic blood pressures. 
d Vital signs will be monitored at hours 0, 1, 4, 6, 12, and 24 (Stage 1) and 0, 1, 4, 6, 11, and 25 (Stage 2). Vital signs should be measured after the blood draws for PK 
assessments if possible. A standard 12-lead ECG will be performed after infusion at all study visits and at the beginning and end of the infusion (approximately 4 hours after the 
start of infusion) for all PK visits. 
e Comprehensive physical examination at Screening and Visit 12; brief physical examination will be performed at other visits where indicated. 
f PROMIS assessments will be administered if a validated instrument is available for the country. 
g Blood sampling is to be performed before the infusion commences or AT2221 is dosed. The blood draw can be taken at the same time as clinical safety sample, which is 
described in the laboratory flowchart. Total GAA protein concentration may be measured as well, as assay sensitivity can be affected by GAA protein. 
h Three blood samples will be taken: one just prior to dosing of AT2221 (if applicable), one just prior to the start of infusion (preferably within 5 to 10 minutes prior to the start of 
infusion), and another approximately 2 hours or halfway through the infusion. For Screening and Baseline visits, the blood draws are to be spaced apart at time points similar to 
PK visit. 
i At Screening, a sample will be obtained. At all other visits, a blood sample will be obtained for IgE determination if a subject has signs of infusion-related reaction or 
anaphylaxis (see Section 11.1.3). The sample should be obtained 6 to 8 hours after the onset of the reaction and at 24 hours for IgE measurement. A third sample is to be drawn 
immediately before the next administration of study drug.Total GAA protein concentration will be measured as well, as assay sensitivity can be affected by GAA protein.  
j The 24-hour PK sample for each PK assessment will be collected on the second day of each visit.  
k Blood samples for plasma GAA activity levels and total GAA protein concentrations are to be taken just prior to initiation of infusion (Time 0) and at times indicated in 
Table 14. 
l Blood sample for plasma GAA activity, total GAA protein, and AT2221 will be collected prior to administration of the oral dose of AT2221. There will be no subsequent serial 
PK blood draws. 
m Blood samples for plasma AT2221 concentrations are to be taken just prior to AT2221 oral administration (Time 0) and at times indicated in Table 14. 
n Infusion solution aliquots will be stored for future analysis as needed. 
o For female subjects of childbearing potential, if applicable. 
p Motor function tests can be performed between Day -7 and Day 0 for baseline measures. 
q Study treatment will not be dispensed to subjects who complete the ET Visit. No infusion solution will be collected.

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Study ATB200-02 Amendment 08 
 
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Table 10: 
Schedule of Assessments for Stages 3 and 4, Cohort 1 Subjects 
Assessments or 
Proceduresa 
Stage 3 Cohort 1 Subjects
b 
Stage 4 
Month 3 
(±3 d) 
Month 6 
(±3 d) 
Month 9 
(±3 d) 
Month 12 
(±3 d) 
Month 15 
(±3 d) 
Month 18 
(±3 d) 
Month 21 
(±3 d) 
Month 24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
AEs, SAEs, IARs, and 
falls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nondrug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient-reported Outcomes 
R-PAct scale 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RHS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS® 
measurements for 
dyspnea, fatigue, 
physical functioning, 
and upper extremitye 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study ATB200-02 Amendment 08 
 
Page 76 of 158 
Table 10: 
Schedule of Assessments for Stages 3 and 4, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 1 Subjects
b 
Stage 4 
Month 3 
(±3 d) 
Month 6 
(±3 d) 
Month 9 
(±3 d) 
Month 12 
(±3 d) 
Month 15 
(±3 d) 
Month 18 
(±3 d) 
Month 21 
(±3 d) 
Month 24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Global Impression of Change 
PGIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SGIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Laboratory Assessments, Immunological Assessments, and Urine Collections 
Serum chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
anti-rhGAA antibodiesf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
assessments of 
neutralizing antibodies
f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
measurement of 
pro-inflammatory 
cytokines and/or other 
biomarkers of immune 
system activationg 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood sample for 
exploratory biomarkers 
of Pompe disease and 
immunogenicityf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for plasma 
GAA total proteinh 
 
 
 
 
 
X 
 

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Study ATB200-02 Amendment 08 
 
Page 77 of 158 
Table 10: 
Schedule of Assessments for Stages 3 and 4, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 1 Subjects
b 
Stage 4 
Month 3 
(±3 d) 
Month 6 
(±3 d) 
Month 9 
(±3 d) 
Month 12 
(±3 d) 
Month 15 
(±3 d) 
Month 18 
(±3 d) 
Month 21 
(±3 d) 
Month 24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
IgE measurementi 
If needed 
Miscellaneous Tests 
Urine pregnancyj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine sample for Hex4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary Function Tests 
SNIP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MIP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MEP 
X 
X 
X 
X 
 X 
X 
X 
X 
X 
FVC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Motor Function Tests 
Gower’s maneuver 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TUG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
10MWT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4-stair climb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GSGC score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6MWT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Muscle Strength Tests 
Manual muscle strength 
by MRC 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc. 
Study ATB200-02 Amendment 08 
Page 78 of 158 
Table 10: 
Schedule of Assessments for Stages 3 and 4, Cohort 1 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 1 Subjects
b 
Stage 4 
Month 3 
(±3 d) 
Month 6 
(±3 d) 
Month 9 
(±3 d) 
Month 12 
(±3 d) 
Month 15 
(±3 d) 
Month 18 
(±3 d) 
Month 21 
(±3 d) 
Month 24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Quantitative muscle 
strength by hand-held 
dynamometer 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Dosing 
AT2221 (260 mg) 
X 
Every other week oral co-administration 
ATB200 (20 mg/kg) 
X 
Every other week infusion co-administration 
Abbreviations: 6MWT = 6-Minute Walk Test; 10MWT = 10-Meter Walk Test; AE = adverse event; anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; 
ECG = electrocardiogram; ET = Early Termination (visit); FSS = Fatigue Severity Scale; FVC = forced vital capacity; GAA = human acid α-glucosidase; GAA = gene that 
encodes human acid α-glucosidase (GAA protein); GSGC = Gait, Stairs, Gower, Chair maneuver; Hex4 = hexose tetrasaccharide; IAR = infusion-associated reaction; 
IgE = immunoglobulin E; MRC = medical research criteria; MEP = maximum expiratory pressure; MIP = maximum inspiratory pressure; PGIC = Physician Global Impression of 
Change; PROMIS = Patient-reported Outcomes Measurement Information System; rhGAA = recombinant human acid α-glucosidase; RHS = Rotterdam Handicap Scale; 
R-PAct = Rasch-built Pompe-specific activity; SAE = serious adverse event; SGIC = Subject Global Impression of Change; SNIP = Sniff Nasal Inspiratory Pressure; 
TUG = Timed Up and Go 
a All study assessments will be performed in the month indicated. 
b Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be followed by safety review by investigators and Amicus Medical Monitor before dosing 
all the other subjects. 
c Sitting vital sign assessments will include measurement of body temperature, rate of respiration, heart rate, and systolic and diastolic blood pressures. 
d Comprehensive physical examinations will be performed during the visits for Month 12, Month 24, and every assessment visit in Stage 4. Brief physical examinations will be 
performed at all other visits. 
e PROMIS assessments will be administered if a validated instrument is available for the country. 
f Blood sampling is to be performed before the infusion commences or AT2221 is dosed. The blood draw can be taken at the same time as clinical safety sample, which is 
described in the laboratory flowchart. Total GAA protein concentration may be measured as well, as assay sensitivity can be affected by GAA protein. 
g Three blood samples will be taken: one just prior to dosing of AT2221 (if applicable), one just prior to the start of infusion (preferably within 5 to 10 minutes prior to the start of 
infusion), and another approximately 2 hours or halfway through the infusion. For Screening and Baseline visits, the blood draws are to be spaced apart at time points similar to 
PK visit. 
h Sparse blood samples for plasma total GAA protein will be taken at any one visit after at least 18 months of ATB200/AT2221 treatment at times indicated in Table 15. 
i A blood sample will be obtained for IgE determination if a subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion reaction (in the opinion of 
the investigator). A blood draw is to be performed 6 to 8 hours after the start of the infusion reaction and at 24 hours for IgE measurement. A third sample is to be drawn 
immediately before the next administration of study drug. Total GAA protein concentration will be measured as well, as assay sensitivity can be affected by GAA protein. 
j For female subjects of childbearing potential, if applicable. 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 79 of 158 
Table 11: 
Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects 
Assessments or 
Proceduresa 
Stage 3 Cohort 2 Subjects
b 
Stage 4 
Screening 
Days -28 to 
-1 
Baseline 
Day 0 
(±1 d) 
Day  
1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month 
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assign subject 
number 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IXRS Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history, 
fall history, and 
prior medications 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
AEs, SAEs, IARs, 
and falls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nondrug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examinationd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 80 of 158 
Table 11: 
Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 2 Subjects
b 
Stage 4 
Screening 
Days -28 to 
-1 
Baseline 
Day 0 
(±1 d) 
Day  
1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month 
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Patient-reported Outcomes 
R-PAct scale 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RHS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS® 
measurements for 
dyspnea, fatigue, 
physical 
functioning, and 
upper extremitye 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Global Impression of Change 
PGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Laboratory Assessments, Immunological Assessments, and Urine Collections 
Serum chemistry 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
anti-rhGAA 
antibodies
f 
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 81 of 158 
Table 11: 
Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 2 Subjects
b 
Stage 4 
Screening 
Days -28 to 
-1 
Baseline 
Day 0 
(±1 d) 
Day  
1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month 
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Blood sample for 
assessments of 
neutralizing 
antibodiesf 
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
measurement of 
pro-inflammatory 
cytokines and/or 
other biomarkers 
of immune system 
activationg 
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood sample for 
exploratory 
biomarkers of 
Pompe disease 
and 
immunogenicityf 
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IgE measurementh 
X 
If needed 
Confirm Pompe 
diagnosis: blood 
sample for GAA 
genotyping if 
needed 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Miscellaneous Tests 
Collect aliquot of 
infusion solution 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Urine pregnancyi 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 82 of 158 
Table 11: 
Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 2 Subjects
b 
Stage 4 
Screening 
Days -28 to 
-1 
Baseline 
Day 0 
(±1 d) 
Day  
1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month 
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Urine sample for 
Hex4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary Function Testsj 
SNIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MEP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FVC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Muscle Strength Testsk 
Manual muscle 
strength by MRC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quantitative 
muscle strength 
by hand-held 
dynamometer 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 83 of 158 
Table 11: 
Schedule of Assessments for Stages 3 and 4, Cohort 2 Subjects (Continued) 
Assessments or 
Proceduresa 
Stage 3 Cohort 2 Subjects
b 
Stage 4 
Screening 
Days -28 to 
-1 
Baseline 
Day 0 
(±1 d) 
Day  
1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month 
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
every 
6 months 
Study Dosing 
AT2221 (260 mg) 
Every other week oral co-administration 
ATB200 
(20 mg/kg) 
Every other week infusion co-administration 
Abbreviations: AE = adverse event; anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; ECG = electrocardiogram; ET = Early Termination (visit); 
FSS = Fatigue Severity Scale; FVC = forced vital capacity; GAA = human acid α-glucosidase; GAA = gene that encodes human acid α-glucosidase (GAA protein); Hex4 = hexose 
tetrasaccharide; IAR = infusion-associated reaction; IgE = immunoglobulin E; IXRS = interactive response technology trial management system; MRC = medical research criteria; 
MEP = maximum expiratory pressure; MIP = maximum inspiratory pressure; PGIC = Physician Global Impression of Change; PROMIS = Patient-reported Outcomes 
Measurement Information System; rhGAA = recombinant human acid α-glucosidase; RHS = Rotterdam Handicap Scale; R-PAct = Rasch-built Pompe-specific activity; 
SAE = serious adverse event; SGIC = Subject Global Impression of Change; SNIP = Sniff Nasal Inspiratory Pressure 
a All study assessments will be performed on the day indicated for each month. 
b Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be followed by safety review by investigators and Amicus Medical Monitor before dosing 
all the other subjects. 
c Sitting vital sign assessments will include measurement of body temperature, rate of respiration, heart rate, and systolic and diastolic blood pressures. 
d Comprehensive physical examinations will be performed at the first visit, and during the visits for Month 12, Month 24, and every assessment visit in Stage 4. Brief physical 
examinations will be performed at all other visits. 
e PROMIS assessments will be administered if a validated instrument is available for the country. 
f Blood sampling is to be performed before the infusion commences or AT2221 is dosed. The blood draw can be taken at the same time as clinical safety sample, which is 
described in the laboratory flowchart. Total GAA protein concentration may be measured as well, as assay sensitivity can be affected by GAA protein. 
g Three blood samples will be taken: one just prior to dosing of AT2221 (if applicable), one just prior to the start of infusion (preferably within 5 to 10 minutes prior to the start of 
infusion), and another approximately 2 hours or halfway through the infusion. For Screening and Baseline visits, the blood draws are to be spaced apart at time points similar to 
PK visit. 
h At Screening, a sample will be obtained. At all other visits, if a subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion reaction (in the 
opinion of the investigator), a blood draw is to be performed 6 to 8 hours after the start of the infusion reaction and at 24 hours for IgE measurement. A third sample is to be 
drawn immediately before the next administration of study drug. Total GAA protein concentration will be measured as well, as assay sensitivity can be affected by GAA protein. 
i For female subjects of childbearing potential, if applicable. 
j Pulmonary function tests and/or assessments will be performed for subjects without invasive ventilatory support only. 
k Muscle strength tests will be performed for upper limbs only. 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 84 of 158 
Table 12: 
Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects 
Assessments or 
Procedures
a 
Stage 3 Cohort 3 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 2 
(±3 d) 
Week 4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assign subject 
number 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IXRS Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history, 
fall history, and 
prior medications 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
AEs, SAEs, IARs, 
and falls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nondrug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs
d, e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination
f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 85 of 158 
Table 12: 
Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 3 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 2 
(±3 d) 
Week 4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Patient-reported Outcomes  
R-PAct scale 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RHS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS® 
measurements for 
dyspnea, fatigue, 
physical 
functioning, and 
upper extremityg 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Global Impression of Change 
PGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Laboratory Assessments, Immunological Assessments, and Urine Collections 
Serum chemistry 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
anti-rhGAA 
antibodies
h 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
assessments of 
neutralizing 
antibodies
h 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 86 of 158 
Table 12: 
Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 3 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 2 
(±3 d) 
Week 4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Blood sample for 
measurement of 
pro-inflammatory 
cytokines and/or 
other biomarkers 
of immune system 
activationi 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood sample for 
exploratory 
biomarkers of 
Pompe disease and 
immunogenicityh 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood samples for 
plasma total GAA 
proteinj 
 
 
 
 
 
 
 
 
 
 
X 
 
IgE measurementk 
X 
If needed 
Confirm Pompe 
diagnosis: blood 
sample for GAA 
genotyping if 
needed 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Assessments (see also Table 14 for time of blood samples)l 
Serial blood 
samples for plasma 
GAA activity 
 
 
X 
Xm 
X 
 
 
 
 
 
 
 
 
 
Serial blood 
samples for plasma 
total GAA protein 
concentration 
 
 
X 
Xm 
X 
 
 
 
 
 
 
 
 
 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 87 of 158 
Table 12: 
Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 3 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 2 
(±3 d) 
Week 4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Serial blood 
samples for plasma 
AT2221 
concentration 
 
 
X 
Xm 
X 
 
 
 
 
 
 
 
 
 
Miscellaneous Tests 
Collect aliquot of 
infusion solutionn 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Urine pregnancyo 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine sample for 
Hex4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary Function Tests 
SNIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MEP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FVC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Motor Function Tests 
Gower’s maneuver 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TUG 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
10MWT 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4-stair climb 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GSGC score 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6MWT 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 88 of 158 
Table 12: 
Schedule of Assessments for Stages 3 and 4, Cohort 3 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 3 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 2 
(±3 d) 
Week 4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Muscle Strength Tests 
Manual muscle 
strength by MRC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quantitative 
muscle strength by 
hand-held 
dynamometer 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Dosing 
AT2221 (260 mg) 
 
 
X 
Every other week oral co-administration 
ATB200 
(20 mg/kg) 
 
 
X 
Every other week infusion co-administration 
Abbreviations: 6MWT = 6-Minute Walk Test; 10MWT = 10-Meter Walk Test; AE = adverse event; Anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; 
ECG = electrocardiogram; ET = Early Termination (visit); FSS = Fatigue Severity Scale; FVC = forced vital capacity; GAA = human acid α-glucosidase; GAA = gene that encodes 
human acid α-glucosidase (GAA protein); GSGC = Gait, Stairs, Gower, Chair maneuver; Hex4 = hexose tetrasaccharide; IAR = infusion-associated reaction; 
IgE = immunoglobulin E; IXRS = interactive response technology trial management system; MRC = medical research criteria; MEP = maximum expiratory pressure; 
MIP = maximum inspiratory pressure; PGIC = Physician Global Impression of Change; PK = pharmacokinetics; PROMIS = Patient-reported Outcomes Measurement Information 
System; rhGAA = recombinant human acid α-glucosidase; RHS = Rotterdam Handicap Scale; R-PAct = Rasch-built Pompe-specific activity; SAE = serious adverse event; 
SGIC = Subject Global Impression of Change; SNIP = Sniff Nasal Inspiratory Pressure; TUG = Timed Up and Go 
a All study assessments will be performed on the day indicated for each visit. 
b Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be followed by safety review by investigators and Amicus Medical Monitor before dosing 
all the other subjects. 
c Stage 4 begins after 2 years in Stage 3. Frequency of assessments is every 6 months. 
d Sitting vital sign assessments will include measurement of body temperature, rate of respiration, heart rate, and systolic and diastolic blood pressures. 
e Vital signs will be monitored at hours 0, 1, 4, 6, 12, and 24 for all PK visits. A standard 12-lead ECG will be performed after infusion at all study visits and at the beginning and 
end of the infusion (approximately 4 hours after the start of infusion) for all PK visits. 
f Comprehensive physical examinations will be performed at the first visit, and during the visits for Month 12, Month 24, and every assessment visit in Stage 4. Brief physical 
examinations will be performed at all other visits. 
g PROMIS assessments will be administered if a validated instrument is available for the country. 
h Blood sampling is to be performed before the infusion commences or AT2221 is dosed. The blood draw can be taken at the same time as clinical safety sample, which is 
described in the laboratory flowchart. Total GAA protein concentration may be measured as well, as assay sensitivity can be affected by GAA protein. 

Amicus Therapeutics, Inc.  
Study ATB200-02 Amendment 08 
 
Page 89 of 158 
i Three blood samples will be taken: one just prior to dosing of AT2221 (if applicable), one just prior to the start of infusion (preferably within 5 to 10 minutes prior to the start of 
infusion), and another approximately 2 hours or halfway through the infusion. For Screening and Baseline visits, the blood draws are to be spaced apart at time points similar to 
PK visit. 
j Sparse blood sampling for plasma total GAA protein will be performed for Cohort 1 and Cohort 3 patients at any one visit after at least 18 months but no more than 24 months of 
ATB200/AT2221 treatment at times indicated in Table 15. 
k At Screening, a sample will be obtained. At all other visits, if a subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion reaction (in the 
opinion of the investigator), a blood draw is to be performed 6 to 8 hours after the start of the infusion reaction and at 24 hours for IgE measurement. A third sample is to be 
drawn immediately before the next administration of study drug. Total GAA protein concentration will be measured as well, as assay sensitivity can be affected by GAA protein. 
l The 24-hour PK sample for each PK assessment will be collected on the second day of each visit (see Table 14). 
m Blood sample for plasma GAA activity, total GAA protein, and AT2221 will be collected prior to administration of the oral dose of AT2221. There will be no subsequent serial 
PK blood draws. 
n Infusion solution aliquots will be stored for future analysis as needed. 
o For female subjects of childbearing potential, if applicable. 

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Table 13: 
Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects 
Assessments or 
Procedures
a 
Stage 3 Cohort 4 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assign subject 
number 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IXRS Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history, 
fall history, and 
prior medications 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
AEs, SAEs, IARs, 
and falls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nondrug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs
d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination
e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 13: 
Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 4 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Patient-reported Outcomes  
R-PAct scale 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RHS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSS 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS® 
measurements for 
dyspnea, fatigue, 
physical 
functioning, and 
upper extremityf 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Global Impression of Change 
PGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Laboratory Assessments, Immunological Assessments, and Urine Collections 
Serum chemistry 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
anti-rhGAA 
antibodies
g 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for 
assessments of 
neutralizing 
antibodies
g 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 13: 
Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 4 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Blood sample for 
exploratory 
biomarkers of 
Pompe disease and 
immunogenicityg 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IgE measurementh 
X 
If needed 
Confirm Pompe 
diagnosis: blood 
sample for GAA 
genotyping if 
needed 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Miscellaneous Tests 
Collect aliquot of 
infusion solutioni 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Urine pregnancyj 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine sample for 
Hex4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary Function Tests 
SNIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MIP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MEP 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FVC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 13: 
Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 4 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Motor Function Tests 
Gower’s maneuver 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TUG 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
10MWT 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4-stair climb 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GSGC score 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6MWT 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Muscle Strength Tests 
Manual muscle 
strength by MRC 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quantitative 
muscle strength by 
hand-held 
dynamometer 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 13: 
Schedule of Assessments for Stages 3 and 4, Cohort 4 Subjects (Continued) 
Assessments or 
Procedures
a 
Stage 3 Cohort 4 Subjects
b 
Stage 4c 
Screening 
Days -28 
to -1 
Baseline 
Day 0 
Day 1 
(±3 d) 
Week 
2 
(±3 d) 
Week 
4 
(±3 d) 
Month 
3 
(±3 d) 
Month 
6 
(±3 d) 
Month 
9 
(±3 d) 
Month 
12 
(±3 d) 
Month
15 
(±3 d) 
Month 
18 
(±3 d) 
Month 
21 
(±3 d) 
Month 
24/ET 
(±3 d) 
Month 
30/ET 
(±7 d) 
Study Dosing 
AT2221 (260 mg) 
 
 
X 
Every other week oral co-administration 
ATB200 
(20 mg/kg) 
 
 
X 
Every other week infusion co-administration 
Abbreviations: 6MWT = 6-Minute Walk Test; 10MWT = 10-Meter Walk Test; AE = adverse event; Anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; 
ECG = electrocardiogram; ET = Early Termination (visit); FSS = Fatigue Severity Scale; FVC = forced vital capacity; GAA = human acid α-glucosidase; GAA = gene that encodes 
human acid α-glucosidase (GAA protein); GSGC = Gait, Stairs, Gower, Chair maneuver; Hex4 = hexose tetrasaccharide; IAR = infusion-associated reaction; 
IgE = immunoglobulin E; IXRS = interactive response technology trial management system; MRC = medical research criteria; MEP = maximum expiratory pressure; 
MIP = maximum inspiratory pressure; PGIC = Physician Global Impression of Change; PROMIS = Patient-reported Outcomes Measurement Information System; 
rhGAA = recombinant human acid α-glucosidase; RHS = Rotterdam Handicap Scale; R-PAct = Rasch-built Pompe-specific activity; SAE = serious adverse event; SGIC = Subject 
Global Impression of Change; SNIP = Sniff Nasal Inspiratory Pressure; TUG = Timed Up and Go 
a All study assessments will be performed on the day indicated for each visit. 
b Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be followed by safety review by investigators and Amicus Medical Monitor before dosing 
all the other subjects. 
c Stage 4 begins after 2 years in Stage 3. Frequency of assessments is every 6 months. 
d Sitting vital sign assessments will include measurement of body temperature, rate of respiration, heart rate, and systolic and diastolic blood pressures. 
e Comprehensive physical examinations will be performed at the first visit, and during the visits for Month 12, Month 24, and every assessment visit in Stage 4. Brief physical 
examinations will be performed at all other visits. 
f PROMIS assessments will be administered if a validated instrument is available for the country. 
g Blood sampling is to be performed before the infusion commences or AT2221 is dosed. The blood draw can be taken at the same time as clinical safety sample, which is 
described in the laboratory flowchart. Total GAA protein concentration may be measured as well, as assay sensitivity can be affected by GAA protein. 
h At Screening, a sample will be obtained. At all other visits, if a subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion reaction (in the 
opinion of the investigator), a blood draw is to be performed 6 to 8 hours after the start of the infusion reaction and at 24 hours for IgE measurement. A third sample is to be 
drawn immediately before the next administration of study drug. Total GAA protein concentration will be measured as well, as assay sensitivity can be affected by GAA protein. 
i Infusion solution aliquots will be stored for future analysis as needed. 
j For female subjects of childbearing potential, if applicable. 

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Table 14: 
Pharmacokinetic Blood Sampling (Cohorts 1 and 3) 
Stage 1: Periods 1, 2, and 3 Cohort 1 
Time from Start of ATB200 IV Infusion (hr) 
 
-1 
0 
1 
2 
3 
3.5 
4 
4.5 
5 
6 
8 
10 
12 
24 
PK Assessmentsa 
Plasma GAA 
activity 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma total GAA 
protein 
concentration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunological Assessments 
Anti-rhGAA 
neutralizing 
antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neutralizing 
antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pro-inflammatory 
cytokinesb 
X 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
IgE measurementc 
If needed 
Stage 2: Periods 4 (Visits 6 and 8) and 5 (Visits 9 and 11) Cohort 1 and Stage 3 Cohort 3 - (Day 1 and Week 4 Visits) 
Time from Start of AT2221 Oral Administration (hr) 
 
0 
1 
1.5 
2 
2.5 
3 
3.5 
4 
4.5 
5 
5.5 
6 
7 
9 
11 
12 
13 
24 
25 
PK Assessmentsa 
 
Plasma GAA 
activity 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
Plasma GAA total 
protein 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 

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Table 14: 
Pharmacokinetic Blood Sampling (Cohorts 1 and 3) (Continued) 
Stage 2: Periods 4 (Visits 6 and 8) and 5 (Visits 9 and 11) Cohort 1 and Stage 3 Cohort 3 - (Day 1 and Week 4 Visits) 
Time from Start of AT2221 Oral Administration (hr) 
 
0 
1 
1.5 
2 
2.5 
3 
3.5 
4 
4.5 
5 
5.5 
6 
7 
9 
11 
12 
13 
24 
25 
Plasma AT2221 
concentrationd 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 
 
X 
Immunological Assessments 
 
Anti-rhGAA 
antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neutralizing 
antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pro-inflammatory 
cytokinesb 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IgE measurement
c 
If needed 
Abbreviations: anti-rhGAA antibodies = antibodies that recognize and can bind to rhGAA; GAA = human acid α-glucosidase; IgE = immunoglobulin E; 
IV = intravenous; PK = pharmacokinetics 
a Blood samples for PK assessments from Time 0 to 13 hours should be completed ± 5 minutes from the indicated target time. The 24- and 25-hour time points 
should be completed ± 1 hour of the indicated target time. 
b Three blood samples will be taken: one just prior to dosing of AT2221 (if applicable), one just prior to the start of infusion (preferably within 5 to 10 minutes 
prior to the start of infusion), and another approximately 2 hours or halfway through the infusion. 
c A blood sample will be obtained for IgE determination if a subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion reaction 
(in the opinion of the investigator). A blood draw is to be performed 6 to 8 hours after the start of the infusion reaction and at 24 hours for IgE measurement. A 
third sample is to be drawn immediately before the next administration of study drug.Total GAA protein concentration will be measured as well, as assay 
sensitivity can be affected by GAA protein levels. 
d Blood samples for plasma AT2221 concentrations are to be taken just prior to AT2221 oral administration (Time 0) and at times indicated. 

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Table 15: 
Sparse Pharmacokinetic Blood Sampling 
Stage 3: Cohorts 1 and 3a - (any one visit after at least 18 months of ATB200/AT2221 treatment) 
Time from Start of AT2221 Administrationb (hr) 
 
1 
2 
2.5 
3 
3.5 
4 
4.5 
5 
5.5 
6 
6.5 
7 
8 
9 
12 
13 
PK Assessmentsb 
Plasma GAA total 
protein 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
a If the subject has completed Stage 3, sparse PK sampling will be performed in Stage 4. 
bSampling times will be shifted by 1 hour earlier for PK analysis and provided this way in the final PK and clinical databases. 

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10.1. 
Description of Study Visits 
Please refer to the schedules of assessments in Table 9, Table 12, and Table 14 for the listing and 
timing of all PK assessments for all visits during the study. 
10.1.1. 
Screening Visit 
All subjects will complete the 1-day Screening Visit up to 4 weeks (or 28 days) before starting 
study treatment. Subjects from Cohorts 2, 3, and 4 who are newly enrolled in the study will 
complete a Screening Visit in Stage 3. 
Assessments may be repeated if requested by the Amicus Medical Monitor. 
The Screening Visit must be registered in the interactive response technology trial management 
system (IXRS) to trigger drug shipment to the site. Refer and comply with detailed guidelines in 
the IXRS manual. 
10.1.2. 
Baseline 
All subjects will complete a Baseline Visit. The Baseline Visit will be Day 0. Functional 
assessments for baseline measures can be performed between Day -7 to Day 0, as it may not be 
possible for a subject to complete them all in a single day. If an assessment is not performed 
during the Baseline Visit, the Screening value may be used as the baseline value. 
Retrospective data for patients from Cohorts 1, 2, and 3: All available data for 6MWT, 
pulmonary function tests, other motor function tests such as 10-meter walk, 4-stair climb, and 
Gower's, quantitative (dynamometry) and qualitative muscle strength tests, Gait, Stairs, Gower, 
and Chair maneuver (GSGC) score, and patient-reported outcomes (PROs), if available should 
be recorded in the Electronic Data Capture (EDC).  
Retrospective data will be gathered from subjects in Cohort 4: At least three 6MWT results, each 
at least 6 months apart must be available and entered in the EDC. At least two 6MWT results 
should be within the past three years. Additionally, pulmonary function tests, other motor 
function tests such as 10-meter walk, 4-stair climb, and Gower's, quantitative (dynamometry) 
and qualitative muscle strength tests, GSGC score, and PROs, if available should be recorded in 
the EDC. In addition to the above requirement, all available data will be collected. 
10.1.3. 
Stage 1, Period 1 (Visit 3, Day 1), Period 2 (Visit 4, Day 15), and Period 3 
(Visit 5, Day 29) (Cohort 1 Subjects Only) 
During Period 1, sentinel dosing will be initiated for the first 2 subjects who receive 
5 mg/kg ATB200. The site may proceed with dosing the remainder of the subjects receiving 
5 mg/kg ATB200, as described in Section 8.2. The same process will be followed for Periods 2 
and 3. 
Dosing for Periods 1, 2, and 3 is as follows: 
• Period 1: Each subject will receive a single IV infusion of 5 mg/kg ATB200 
• Period 2: Each subject who has completed Period 1 will receive a single IV infusion 
of 10 mg/kg ATB200 

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• Period 3: Each subject who has completed Period 2 will receive a single IV infusion 
of 20 mg/kg ATB200 
10.1.4. 
Stage 2, Period 4: Visit 6 (Day 43), Visit 7 (Day 57), and Visit 8 (Day 71) 
(Cohort 1 Subjects Only) 
For Period 4 (Visit 6 and Visit 8), the same assessments indicated for Period 1, Period 2, and 
Period 3 will be performed for all subjects who have completed Period 3 (refer to Section 10.1.3 
and Table 9).  
At Visit 7, only a pre-dose blood sample will be taken for plasma GAA activity levels, total 
GAA protein concentration, and AT2221 concentration. No post-dose PK blood samples will be 
taken.  
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of oral 
AT2221. 
10.1.5. 
Stage 2, Period 5: Visit 9 (Day 85), Visit 10 (Day 99), and Visit 11 (Day 113) 
(Cohort 1 Subjects Only) 
For Period 5 (Visit 9 and Visit 11), the same assessments indicated for Period 1, Period 2, and 
Period 3 will be performed for all subjects who have completed Period 4 (refer to Section 10.1.3 
and Table 9). 
At Visit 10, only a pre-dose blood sample will be taken for plasma GAA activity level, total 
GAA protein concentration, and AT2221 concentration. No post-dose PK blood samples will be 
taken.  
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of oral 
AT2221. 
10.1.6. 
End of PK: Visit 12 (Day 127)  
Assessments to be performed at the End of PK Visit are outlined in Table 9. The End of PK Visit 
will be considered Day 1 of Stage 3 for the subjects in Cohort 1. Subjects will receive 20 mg/kg 
ATB200 and 260 mg AT2221 at this visit. 
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of oral 
AT2221. 
10.1.7. 
Stage 3: PK Sampling for Cohort 3 Subjects 
All subjects will receive 20 mg/kg ATB200 and 260 mg AT2221 on a biweekly (every other 
week) basis in Stage 3. For Cohort 3 subjects, for the first and third doses of 20 mg/kg ATB200 
and 260 mg AT2221 at Day 1 and Week 4, serial blood samples for plasma GAA activity levels, 
total protein, and AT2221 will be performed according to Table 9. Cohort 4 will have no PK 
sampling. 
At Visit 2, a blood sample for plasma GAA activity levels, total GAA protein concentration, and 
AT2221 will be collected prior to administration of the oral dose of AT2221. There will be no 
subsequent serial PK blood draws in Stage 3. 

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Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of oral 
AT2221. 
10.1.8. 
Stage 3: Sparse PK Sampling for Cohorts 1 and 3 Subjects 
After at least 18 months of ATB200/AT2221 treatment in Stage 3, all Cohort 1 and 3 subjects 
will have sparse blood sampling for plasma total GAA protein taken for estimation of AUC and 
total plasma clearance (CLT) by compartmental or population PK modeling as indicated in 
Table 15. If the subject has completed Stage 3, the assessment will be performed in Stage 4. 
10.1.9. 
Stage 4: Open-label Extension 
All subjects will receive 20 mg/kg ATB200 and 260 mg AT2221 on a biweekly basis in Stage 4. 
Functional assessments will be performed every 6 months.  
Note: Subjects are required to fast at least 2 hours before and 2 hours after administration of oral 
AT2221. 
10.1.10. 
Early Termination Visit/End of Study  
Subjects who discontinue early from the study will no longer receive study treatment, regardless 
of study stage. They will undergo the same assessments as for the Month 24 Visit. Assessments 
are outlined in Table 9, Table 10, Table 11, Table 12, and Table 13.  
Upon study completion or subject discontinuation, subjects who are confirmed positive for 
anti-rhGAA antibodies will complete 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 1-, 3-, 6-, 9-, and 
12-months follow-up) or until they begin treatment with another ERT or investigational therapy. 
If anti-rhGAA antibodies are not confirmed positive at follow-up time points earlier than 
6 months, no further testing is required. 
10.1.11. 
Follow-up Period 
The follow-up period has one visit or telephone call. This visit will occur within 1 month after 
the last treatment visit unless the subject enters a separate study protocol or other program 
depending on local regulations. At the follow-up visit, the following assessments and procedures 
will be performed: weight, vital signs, physical examination, serum chemistry, hematology, urine 
pregnancy test (all females of childbearing potential), urinalysis, ECG, and recording of 
concomitant medications and adverse events. If the patient does not return for the follow-up visit, 
information will be collected about concomitant medications and adverse events via telephone 
call. 
10.1.12. 
Unscheduled Visits 
Unscheduled visits for medical reasons such as evaluation of AEs and additional laboratory tests 
and/or other investigations to further clarify an abnormal test/assessment result can be performed 
at any time at the investigator’s discretion or if requested by the Amicus Medical Monitor. The 
date and reason for the visit, in addition to information collected from procedures performed, 
should be captured in the subject’s medical record and/or on appropriate eCRFs. 

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10.2. 
Description of Study Assessments  
The following assessments or procedures are described in order of their appearance in the 
Schedule of Assessments and Procedures (Table 9, Table 10, Table 11, Table 12, and Table 13). 
Additional information on collection, processing, and shipping procedures for all samples will be 
provided in a supporting laboratory flowchart. Details of functional assessments are provided in 
the corresponding study functional assessment manual. 
Any study procedures that involve supine positions may be deferred if the subject is unable to 
complete them in a supine position. 
Due to the amount of time required to perform the functional assessments (ie, 6MWT, motor 
function tests, muscle strength tests, and pulmonary function tests), these tests may be scheduled 
either the day before or day after the subject’s infusion date if the combination of the functional 
assessments and the infusion procedure is too burdensome for the subject if performed on the 
same day. 
If a subject is ill or injured at a scheduled visit, the functional assessments may be deferred to 
when the subject’s condition has improved, in consultation with the Medical Monitor. 
10.2.1. 
Informed Consent 
Please refer to Section 15.2.1.  
10.2.2. 
Demographics 
Demographic data to be collected at Screening and includes date of birth and sex. In the US, race 
and ethnicity will also be recorded. 
10.2.3. 
Medical History, Fall History, and Prior Medications  
Medical history (including FVC and 6MWT, plasma CK, ALT, AST, and urine Hex4 lab results) 
including information on medications and procedures used to treat/manage each medical 
condition will be collected at the Screening Visit. This will include a history of falls over the last 
year. Study staff should complete a structured review of prior medications that are prohibited 
(Section 8.7) to ensure eligibility and should review again both the medical history (as listed 
above) and prior medications at Baseline Visit. Details are to be recorded for any past IARs 
(including intensity, start date, stop date, and outcome), medication use to manage symptoms 
(including dosage, frequency of administration, start date, and stop date), and any laboratory 
tests that were obtained as part of the assessment of IARs. Refer to Section 11.1.3 for further 
information on IARs. In addition, all available information on prior Ab titers and neutralizing 
antibodies associated with prior ERT use, including the assay technology and the facility where 
the assay(s) were performed, will be collected in the source documentation for subjects in 
Cohorts 1 and 2. 
10.2.4. 
Adverse Events and/or Serious Adverse Events 
Throughout the study, subjects will be given an opportunity to report AEs. The definitions, 
reporting, and follow-up of AEs and SAEs are described in Section 11.1.1. 

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Sentinel dosing for the first 2 sentinel subjects during all periods and in all stages will be 
followed for safety review by investigators and Amicus Medical Monitor before dosing all the 
other subjects. 
10.2.5. 
Concomitant Medications and Nondrug Therapies  
At each visit, subjects will be asked to report any medications (dosage, frequency, start date, and 
stop date) and procedures unreported since last visit. 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. Concomitant medications 
will be coded using the World Health Organization Medical Dictionary (WHOMD). 
10.2.6. 
Vital Signs, Weight, and Height 
Sitting vital sign assessments will include measurement of body temperature, respiration, heart 
rate, and systolic and diastolic blood pressures at times noted in Table 9, Table 10, Table 11, 
Table 12, and Table 13. During blood sample collection for PK assessments for Cohorts 1 and 3, 
vital signs will be taken after selected blood samples.  
During Stage 3, the subject weight will be measured at 3 month intervals in all cohorts. This 
weight will be used to revise the dose calculation of ATB200 if there has been a change since the 
previous 3 month measurement. 
During Stage 4, the subject weight will be measured at 6 month intervals in all cohorts. This 
weight will be used to revise the dose calculation of ATB200 if there has been a change since the 
previous 6 month measurement. 
Note: For visits where a subject is administered a new ATB200 dose level for the first time, vital 
signs will be monitored for the first 12 hours after the start of infusion. During the 48 hour 
observations period vital signs will be monitored, at a minimum, every 6 to 8 hours until the end 
of the 48-hour observation period. 
10.2.7. 
Physical Examination 
Subjects in Cohort 1 will undergo comprehensive or brief PEs according to the Schedule of 
Assessments tables. Any clinically significant (CS) abnormal observation, newly emerged, or 
worsened, during the study should be reported as an AE. 
10.2.8. 
Electrocardiogram 
A standard 12-lead ECG will be performed at visits indicated in the Schedule of Assessments 
tables. For PK visits, ECGs are performed at 2 time points: before dosing and at the end of the 
infusion (approximately 4 hours after the start of the infusion). Subjects will rest for 
approximately 5 minutes before the ECG recording begins and will be in the supine position 
throughout the ECG evaluation. Significant findings not present prior to or worsening after the 
start of treatment (ie, Baseline), which meet the definition of an AE, must be recorded in the 
eCRF. 

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10.2.9. 
Patient-reported Outcomes (Including Pompe-associated Scales)  
Patient-reported outcomes (PROs) to be assessed during this study include R-PAct Scale, 
Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS), and Patient-reported Outcomes 
Measurement Information System (PROMIS®) instruments (for dyspnea, fatigue, physical 
functioning, and upper extremity), and will be administered at Baseline, at the end of Stage 2 for 
Cohort 1, every 3 months in Stage 3 and every 6 months in Stage 4 for all subjects. The subject 
should be given the questionnaires to complete at the scheduled visit before any study related 
procedures take place.  
Subjects who have already initiated study drug treatment in this study should complete the 
PROMIS instruments from the perspective of their experience immediately prior to study entry. 
For these subjects, this retrospective recall will be done only once. All other instances will reflect 
current experience. 
The PRO tools are provided in Appendix 3, Appendix 4, Appendix 5, and Appendix 6. Countries 
in which the PRO tools are validated are noted in Appendix 7. 
10.2.10. 
Global Impression of Change 
The Subject Global Impression of Change (SGIC) and Physician Global Impression of Change 
(PGIC) will only be administered in Stage 3 and 4 as indicated in the Schedule of Assessments 
tables. The administrator of the SGIC will read the questions to the subject. 
The Global Impression of Change tools are provided in Appendix 8. 
10.2.11. 
Clinical Safety Laboratory Tests  
The collection, processing, and shipment of clinical laboratory samples will be fully described in 
the study laboratory flowchart. The parameters measured in the serum chemistry, hematology, 
and urinalysis are summarized in Table 16, Table 17, and Table 18, respectively. Blood and 
urine samples for clinical laboratory evaluations will be taken before study treatment 
administration in Stages 1, 2, 3, and 4 and will be collected according to the Schedule of 
Assessments tables. 
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”. Any results which are considered CS should be confirmed in a repeat test 
at the investigator’s discretion. The investigator should consider repeat testing of persistent CS 
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.  
All CS laboratory results will be reported as an AE or SAE, as appropriate. 
If any results demonstrate, in the investigator’s opinion, a CS abnormality that the subject has 
not previously experienced, then the subject should be asked to return as soon as possible for an 
unscheduled visit, so that repeat specimens can be obtained. 
Clinically significant values are provided in Appendix 2. 
10.2.11.1. Serum Chemistry  
The serum chemistry parameters are described in Table 16.  

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Table 16: 
Serum Chemistry Parameters 
ALT 
Creatinine 
Alkaline phosphatase 
Gamma–glutamyltransferase 
AST 
Glucose 
Albumin 
Lactate dehydrogenase (LDH) 
Bilirubin, total  
Magnesium 
Blood urea nitrogen  
Phosphorous 
Calcium, total 
Potassium 
Carbon dioxide, total (bicarbonate) 
Protein, total 
Chloride 
Sodium 
Creatine phosphokinase (CK) 
Uric acid 
10.2.11.2. Hematology 
The hematology parameters are described in Table 17. 
Table 17: 
Hematology Parameters  
Platelet count 
Automated WBC Differential 
Red blood cell count 
Neutrophils 
WBC count (absolute) 
Lymphocytes 
Hematocrit  
Monocytes 
Hemoglobin 
Eosinophils 
MCV 
Basophils 
10.2.11.3. Urinalysis 
Urinalysis parameters are described in Table 18. 
Table 18: 
Urinalysis Parameters 
Color 
Ketones  
Appearance 
Blood  
Specific gravity 
WBC 
pH 
Nitrite  
Protein 
Bilirubin 
Glucose 
Microscopy of sediment 

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10.2.12. 
Immunogenicity Assessments 
Blood samples for measurement of anti-rhGAA antibodies (total, neutralizing, and 
cross-reactive) will be collected at visits indicated in the tables of assessments and collection is 
to be performed before the infusion commences or AT2221 is dosed. The blood draw can be 
taken at the same time as clinical safety sample. Sample collection and processing instructions 
will also be provided in the study laboratory flowchart. 
Anti-rhGAA total antibodies and antibodies cross-reactive to alglucosidase alfa will be 
determined. Upon study completion or subject discontinuation, subjects who are confirmed 
positive for anti-rhGAA antibodies will complete 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 1-, 3-, 6-, 
9-, and 12-months follow-up) or until they begin treatment with another ERT or investigational 
therapy. If anti-rhGAA antibodies are not confirmed positive at follow-up time points earlier 
than 6 months, no further testing is required. 
Neutralizing antibody assays may include: 
• Inhibition of ATB200-mediated hydrolysis of  
4-methylumbelliferyl-α-D-glucopyranoside (4-MU-α Glc) 
• Inhibition of ATB200-mediated hydrolysis of glycogen 
• Inhibition of ATB200 binding to CI-MPR 
At Screening, a blood sample will be collected for immunoglobulin E (IgE) for all subjects. If a 
subject experiences anaphylaxis as defined in Appendix 1 or a moderate to severe infusion 
reaction (in the opinion of the investigator), 3 blood draws will be required for measurement of 
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. Total GAA protein concentration will be measured from the same 
blood draw sample as assay sensitivity can be affected by GAA protein levels. 
10.2.13. 
Pro-inflammatory Cytokines and Other Biomarkers of Immune System 
Activation 
Blood samples for pro-inflammatory cytokines and other biomarkers of immune system 
activation will be drawn at study visits as indicated in Table 14 (PK Blood Sampling). These 
blood samples will not be drawn for any cohorts in Stage 4 nor for Cohort 4 in Stage 3. 
10.2.14. 
GAA Genotyping 
At Screening, a blood sample will be collected from subjects for GAA gene sequencing to 
identify GAA genotypes that may be associated with Pompe disease (for subjects unable to 
provide GAA genotyping report during Screening). 
10.2.15. 
Pharmacokinetic Blood Sampling 
Serial blood samples for plasma GAA activity levels, total GAA protein concentration, and 
plasma AT2221 concentrations in Stages 1 and 2 for subjects from Cohort 1 and in Stage 3 for 
subjects from Cohort 3, will be performed at selected time points detailed in PK Blood Sampling 
(Table 14) and indicated in Table 9 and Table 12. Total GAA activity levels for 5, 10, and 

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20 mg/kg ATB200 in plasma will be determined by a validated enzymatic assays using 
4-MU-α Glc substrate. Total GAA protein concentrations in plasma for 5, 10, and 20 mg/kg 
ATB200 will be determined by a validated liquid chromatography–tandem mass spectroscopy 
(LC-MS/MS) quantification of rhGAA-specific “signature” peptide(s). Plasma AT2221 
concentrations for 130 mg and 260 mg AT2221 will be determined by a validated LC-MS/MS 
assay. 
Blood samples for plasma GAA activity, total GAA protein, and AT2221 determinations will be 
taken as follows: 
• Stage 1, a blood sample will be collected from subjects who are enrolled in Cohort 1 
for plasma GAA activity levels and total GAA protein only, just prior to initiation of 
infusion (Time 0) and post-dose at time points detailed in Table 9. 
• A blood sample will be collected from subjects who are enrolled in Cohort 1 in 
Stage 2 and Cohort 3 in Stage 3 for plasma GAA activity levels, total plasma GAA 
protein, and plasma AT2221 concentration just prior to AT2221 administration 
(Time 0) and post-dose at time points detailed in Table 14 and indicated in Table 9 
and Table 12. 
• Blood samples for PK assessments from Time 0 to 12 hours should be completed 
± 5 minutes from the indicated target time. The 25-hour time point should be 
completed ±1 hour of the indicated target time. The 24 and 25-hour PK samples will 
be collected on the second day of each visit. 
Additional information on the sample collection, sample handling, and sample analysis are 
provided in a separate study laboratory flowchart. 
10.2.16. 
Aliquot of Infusion Solution 
A 0.5 to 1 mL sample of the prepared ATB200 infusion solution will be collected from the 
infusion bag immediately before and immediately after the ATB200 infusions (before flushing 
the line) at visits indicated in the Schedule of Assessments. This sample may be analyzed for 
total ATB200 protein or aggregation. The time and date of each preparation of ATB200 infusion 
solution must be recorded. 
10.2.17. 
Pregnancy Test 
All female subjects of childbearing potential (as defined in Section 11.6.1) will have a urine 
pregnancy test performed at every study visit, except baseline.  
10.2.18. 
Urinary Hex4 
Urine samples for Hex4 determination will be collected at every scheduled visit (except 
Baseline) in Stages 1 and 2, every 3 months in Stage 3, and every 6 months in Stage 4 (see 
Table 9, Table 10, Table 11, Table 12, and Table 13). Hexose tetrasaccharide concentrations are 
to be determined by stable isotope dilution-electrospray ionization-tandem mass spectrometry 
with multiple reaction monitoring. Sample handling and shipment instructions will be outlined in 
the study laboratory flowchart. 

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10.2.19. 
Pulmonary Function Tests (PFTs)/Spirometry 
The following pulmonary function tests (PFTs) and/or assessments will be performed at the 
Baseline, every 3 months in Stage 3 and every 6 months in Stage 4 for all ambulatory and 
nonambulatory subjects without invasive ventilatory support and at the end of Stage 2 for 
Cohort 1. Detailed instructions for the PFT assessments will be provided in the corresponding 
section of a separate study procedure manual. 
Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and Sniff Nasal 
Inspiratory Pressure (SNIP) will be assessed using the Carefusion MicroRPM manometer. The 
subjects will be seated comfortably with back and feet supported (feet on floor). 
Forced vital capacity (FVC) will be assessed in sitting and supine positions using the nSpire 
KoKo® PFT Spirometer.  
10.2.20. 
Motor Function Tests – Ambulatory Subjects Only 
Motor function tests will be performed at Baseline for all subjects, at the end of Stage 2 for 
Cohort 1, every 3 months in Stage 3 and every 6 months in Stage 4 for all subjects in the order 
indicated in Table 9, Table 10, Table 11, Table 12, and Table 13. Motor function tests can be 
performed between Day -7 and Day 0 for baseline measures. Detailed instructions for these 
tests/assessments will be provided in a separate study procedure manual(s). 
10.2.20.1. 6-Minute Walk Test (6MWT) 
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.  
In the event of an invalid test, the subject may be offered the opportunity to repeat the 6MWT. 
The retest may occur immediately after the completion of the invalid 6MWT (following a rest 
period – minimum of 10 minutes) or the next day, based upon the judgment of the physical 
therapist and the investigator. 
10.2.20.2. Gower’s Maneuver  
This test involves measuring the time it takes a subject lying supine on the floor to get to a 
standing position. Subjects may use the floor or their legs, but the test must be performed without 
the assistance of any furniture.  
10.2.20.3. Timed Up and Go (TUG) 
The general information regarding Timed Up and Go; a timed test used to assess mobility (TUG) 
has been derived from Podsiadlo and Richardson (1991). The test involves a seated subject 
getting up from a standard armchair, walking to a line that is 3 meters (9.8 feet) long, turning 
around at the line, walking back to the chair, and sitting back down. The test begins when the 
subject’s buttocks begins to lift from the seat and ends when the subject’s buttocks touches the 
seat. 
10.2.20.4. 10-Meter Walk Test (10MWT) 
This timed walk test should be performed with walking shoes on a flat surface. The purpose of 
this test is to traverse the distance of 10 meters as fast and safely as possible.  

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10.2.20.5. 4-Stair Climb 
This test is performed with the use of “4 standard stairs.” This test will document the time to 
climb 4 standard stairs and will assist in assignment of the appropriate lower extremity functional 
grade for those individuals who are ambulatory.  
10.2.20.6. Gait, Stairs, Gower, and Chair Maneuver (GSGC) Score  
The GSGC score is obtained by adding the scores attributed to each functional test (gait by 
walking 10 meters, climbing 4 stairs, Gower’s maneuver, and rising from a chair) according to 
how the subject performed them and might vary from a minimum of 4 (normal performance) to a 
maximum of 27 (worst score). 
10.2.21. 
Muscle Strength Tests – All Subjects 
Manual muscle strength will be tested by medical research criteria (MRC) scale. All efforts 
should be made to maintain the same rater and method throughout the subject’s participation in 
the study. Muscle strength will also be measured using a hand-held dynamometer. Muscle 
groups tested include shoulder abductors, shoulder adductors, hip flexors, hip abductors, hip 
adductors (for hip adductors, hand held dynamometer only), knee extensors, knee flexors, elbow 
extensors, and elbow flexors.  
Nonambulatory subjects will perform muscle strength tests for upper limbs only. 
These assessments will be performed at baseline and Stage 3 and 4 as indicated in Table 9, 
Table 10, Table 11, Table 12, and Table 13. 
Detailed instructions for these tests will be provided in a separate study procedure manual. 
10.3. 
Biological Specimen 
Any biological specimens remaining at the end of the study may be used for future exploratory 
analyses 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. Future genetic testing will not be conducted for retained samples. 
10.4. 
High Sustained Antibody Titer 
High sustained antibody titer is defined as subjects with anti-GAA antibody titer of 1:51,200 or 
higher from the 2 most recent tests using Genzyme’s or comparable method prior to screening. If 
a comparable method is used, it should be discussed with the Amicus Medical Monitor. 
10.5. 
Infusion Only Visits 
In Stage 3 and 4, ATB200 is to be administered every 2 weeks as an IV infusion in combination 
with oral AT2221. Changes in the protocol prescribed duration of ATB200 infusion due to safety 
or tolerability issues will be documented in the eCRF. During these Infusion Only Visits, in 
addition to receiving the study treatment, AE/SAE will be collected. Each site should follow 
their facility guidelines for performing infusions to monitor vital signs or other safety processes 
that may be in place. These Infusion Only Visits are not outlined in the Schedule of Assessments. 

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10.6. 
Home Infusion  
Subjects participating in the study will be considered eligible for administration of 
ATB200/AT2221 on location at their home or residence after having received ATB200/AT2221 
administrations in the study for a period of at least 6 months and not having experienced an IAR 
for a period of 6 months prior to last infusion. Subjects with history of severe IARs are not 
eligible for home infusions; subjects with a history including a life-threatening IAR are not 
eligible for home infusions. Eligible subjects may request participation in the Home Infusion 
Program with requests granted on a case-by-case basis following discussion between the Medical 
Monitor and PI with prior approvals granted by Institutional Review Boards (IRBs)/Ethics 
Committees (ECs), and Regulatory Authorities (RAs). Administration of ATB200/AT2221 will 
be performed at home for eligible subjects by a trained research home infusion nurse provided by 
an Amicus designated service provider. All subjects participating in the Home Infusion Program, 
will be required to complete all functional assessments at their primary site as defined in the 
protocol. Safety monitoring at home including reporting of AEs, SAEs, and IARs is performed 
by home infusion nurse. Refer to Section 11.1.3 for further information on IARs, including their 
reporting and management.The home infusion nurse will document and report the findings direct 
to sites after every infusion as detailed in the manual for home infusion. 
Pre-requisites Criteria: 
Inclusion Criteria: 
• Received ATB200/AT2221 treatment for a minimum of one year  
• Meets following requirements regarding feasibility of the home site for ERT infusion: 
− Availability of utilities and equipment required for storage of Drug Product upon 
receipt  
− Accessibility for delivery of Drug Product and associated supplies 
−  Accessibility of trained home infusion nurse for preparation/administration 
− Preparation of ATB200 lyophilized drug product for reconstitution 
− Infusion of large volume parenteral product 
− Disposal of waste and discarding of used medical supplies 
• Amicus/designee deems the home site to be appropriate for home infusion following 
home assessment 
• PI agrees to collaborate with the home infusion agency/home infusion nurse with 
respect to providing advice and support as needed by the home infusion nurse 
Exclusion Criteria: 
• Any IAR in the past 6 months or recurrent severe or life-threatening IAR including 
anaphylaxis at any time. 

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11. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
The definition of an AE is presented in Section 11.1.1. For each subject, reporting of AEs begins 
at the time written informed consent is provided. Investigators are responsible for reporting AE 
information to Institutional Review Boards (IRBs), International Ethics Committees (IECs), or 
Research Ethics Boards (REBs) in accordance with the requirements of their institutions. 
11.1. 
Definitions  
11.1.1. 
Adverse Events 
An AE is any untoward medical occurrence in a 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 (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medical product, whether or not considered related to the medical product. Adverse events may 
include the onset of new illness and the exacerbation of pre-existing conditions. 
The routine evolution of the disease condition under treatment according to the protocol will be 
evaluated as part of the disease symptoms assessments. Changes in Pompe disease symptoms 
must be reviewed by the investigator or a medically qualified sub-investigator and be recorded as 
“Clinically Significant” or “Not Clinically Significant” in subjects’ source records. Changes in 
the disease condition may not qualify as AEs. However, if there is a clinically relevant 
worsening of a sign or symptom of the condition under treatment and the outcome fulfills the 
definition of an AE, it must be reported as directed in the protocol. 
Any AE that begins after the first dose of study medication (ATB200 and/or AT2221) will be 
considered a TEAE. 
Subjects experiencing AEs should be followed until their health has returned to baseline status or 
stabilized or have otherwise been explained. 
11.1.2. 
Serious Adverse Events  
An SAE is any AE occurring at any dose that results in any of the following outcomes: 
• Death. 
• Life-threatening, as assessed by either the investigator or Amicus (places the subject 
at immediate risk of death from the AE as it occurs; it does not refer to an event 
which hypothetically might have caused death if it were more severe). 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• Requires in-patient hospitalization (ie, admission to hospital, regardless of duration) 
or prolongs existing hospitalization. 
− Complications arising during hospitalization are AEs or SAEs, depending on 
nature of the event, and must be reported as described in this protocol. 
− Medications administered during hospitalization must be recorded in the 
Concomitant Medications eCRF module. 

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• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline does not have to be reported as an SAE provided the planned treatment 
is documented in Screening Visit source records. If not documented in the 
Screening Visit source records, an SAE report is required. Outpatient procedures 
performed in a hospital do not qualify as an SAE.  
• Is a congenital anomaly/birth defect. 
An important medical event that may not result in one of the above serious outcomes may be 
considered an SAE when, based upon appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the 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 in-patient 
hospitalization, or development of drug dependency or drug abuse. 
For all subjects, AEs and SAEs will be reported from time of informed consent signing, until 
30 days after end of study participation. 
11.1.3. 
Infusion-associated Reactions 
An IAR is 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, 
immediate 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 
Immediate-type 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-type reactions first manifest more than 24 hours post infusion, usually 1 to 3 days 
post infusion. The most common symptoms of late-type infusion reactions are pruritic skin 
eruptions, fever, malaise, and polyarthralgia. 
Any symptom or sign occurring during or within 2 hours of completion of the infusion should be 
reported as an immediate-type IAR and deemed drug-related AE, unless an alternative obvious 
explanation exists, eg, mechanical fall. Any symptom or sign occurring between 2 and 24 hours 
will be recorded as an IAR if it fits within the description of an IAR in the investigator’s opinion. 
It would be reported as immediate-type IAR and deemed a drug-related AE. 

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Any symptom or sign occurring between 24 and 96 hours after completion of the infusion that, in 
the investigator’s opinion, fits the clinical description of a symptom or sign associated with an 
IAR should be reported as a late-type IAR and deemed a drug-related AE. 
A symptom or sign that occurs 24 hours or later and in the investigator’s opinion is possibly, 
probably, or likely an IAR should be reported as such and deemed drug-related AE. 
Note: The list of IAR symptoms provided in Table 19 is not comprehensive. It is meant to serve 
as a guideline to the investigators to report and manage IAR as AE. Table 19 also provides a 
guideline for management of IARs and anaphylaxis (see also Appendix 1). It is at the 
investigator’s discretion to follow the guidelines or implement treatment protocol that their 
center is accustomed to following. 
In the event that a subject experiences an IAR, the subject should be premedicated for 
subsequent infusions with antihistamines, steroids, and/or acetaminophen. The premedications 
should be continued for a period of up to 1 year. Decision regarding discontinuation of 
premedications should occur only after discussion with Amicus Medical Monitor. 
Table 19: 
Guidelines for Management of Immediate 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/paracetamol and/or 
IV antihistamine. 
Prepare emergency equipment for any subsequent study 
treatment escalation. 
Subject must be observed at site or medical facility for 
2-4 hours after resolution of the symptoms. 
Record all details of times, concomitant medications, and 
infusion rates. 
Draw IgE and total GAA sample 6 to 8 and 24 hours after 
the start of the infusion reaction (2 samples). 
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 

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Table 19: 
Guidelines for Management of Immediate Infusion-associated Reactions 
(Continued) 
Severity 
Symptoms (such as, 
but not restricted to) 
Management Guidelines 
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 
PI/designee. 
Continue management as directed by the PI/designee. 
Watch for at least 1 hour after resolution of symptoms. 
If deemed appropriate by PI/investigator, resume study 
treatment infusion at reduced rate and prepare emergency 
equipment. 
If deemed appropriate by PI/investigator, 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 SAE if criteria for SAE reporting 
are met. 
Draw IgE and total GAA sample 6 to 8 and 24 hours after 
the start of the infusion reaction (2 samples). 

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Table 19: 
Guidelines for Management of Immediate Infusion-associated Reactions 
(Continued) 
Severity 
Symptoms (such as, 
but not restricted to) 
Management Guidelines 
Severe 
reaction, 
anaphylaxis, 
or anaphylac-
toid 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 
PI/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 PI/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 PI/investigator, study treatment 
infusion can be re-initiated 7 to 14 days with premedications 
and at the 4-hour duration. 
Draw IgE and total GAA sample 6 to 8 and 24 hours after 
the start of the infusion reaction (2 samples). 
Report SAE if criteria for SAE reporting are met. 
Abbreviations: GAA = human acid α-glucosidase; IgE = immunoglobulin E; IM = intramuscular; IV = intravenous; 
NS = normal saline; PI = Principal Investigator; SAE = serious adverse event; WFI = water for injection  
Sources: Vogel 2010; Sampson et al 2006 
11.2. 
Relationship to Study Treatment 
The investigator or a medically qualified sub-investigator will review each event and assess its 
relationship to study treatment based on available information according to the following 
guidelines: 
• Definite: A reaction that follows a distinct temporal relationship from administration 
of study treatment; that follows a known reaction to the agent or chemical group of 

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the study treatments; and that cannot be explained by the subject’s clinical state or 
other factors. 
• Probable: A reaction that follows a reasonable temporal sequence from administration 
of study treatment; that follows a known or expected response pattern to the 
suspected study treatment; 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 study treatment; that follows a known or expected response pattern to the 
suspected study treatment; but that could readily have been produced by a number of 
other factors. 
• Unlikely: A reaction that does not follow a reasonable temporal sequence from 
administration of study treatment. However, causality from study treatment cannot be 
ruled out. 
• Unrelated: A reaction for which sufficient data exist to indicate that the etiology is 
unrelated to study treatment. 
For the purpose of reporting SAEs to regulatory authorities and IRBs/ECs, any AE assessed by 
the investigator as definitely, probably, or possibly related to ATB200 and/or AT2221 will be 
considered “related” to study treatment (ie, associated with the use of study treatment). Any AE 
assessed as unlikely or unrelated will be considered “not related” to study treatment (ie, not 
associated with the use of study treatment). 
11.3. 
Assessment of Intensity 
The following definitions for rating intensity will be used for all AEs: 
• 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 intensity rests on medical judgment, the determination of 
intensity must be made with the appropriate involvement of the investigator or a medically 
qualified sub-investigator. 
It is important to distinguish the difference between SAEs and events that are deemed as severe 
in intensity. Adverse events of severe intensity are not serious if one of the definitions in 
Section 11.1.2 is not met; AEs of any intensity must be reported as SAEs if one of the definitions 
in Section 11.1.2 is met. 
11.4. 
Reporting Adverse Events 
Information regarding AEs is to be obtained by questioning or examining subjects. 

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At each visit, beginning from the time written informed consent is provided until 30 days after 
the last treatment visit, all new complaints and symptoms (ie, those not existing before subjects 
provide informed consent) must be recorded as AEs in the eCRF and in subjects’ source records. 
Findings documented on Screening ECGs that are unknown to subjects (ie, asymptomatic 
subjects) should be recorded as medical history (inclusive of FVC and 6MWT, plasma CK, ALT, 
AST, and urine Hex4 lab results). 
• Pre-existing complaints or symptoms that worsen (eg, increase in intensity, 
frequency) after subjects provide informed consent must be entered in the AE eCRF 
module. 
• CS laboratory abnormalities must be reported by the investigator as an AE or SAE as 
appropriate. 
• CS changes to Screening ECG results must be reported by the investigator as an AE 
or SAE as appropriate. CS values will be provided in Appendix 2. 
• AEs related to a protocol-required procedure. 
For each reported AE, the date the event started and ended, action taken, outcome (resolved, 
resolved with sequelae, ongoing, or fatal), intensity, and relationship to study treatment must be 
noted. Every effort should be made to report the start and end time AEs occurred. 
All subjects who have AEs, whether or not events are considered associated with the use of 
ATB200 administered as a single agent or the use of ATB200 co-administered with AT2221, 
must be monitored to determine the outcome. The clinical course of AEs will be followed 
according to accepted standards of medical practice, even after the end of the study, until their 
health has returned to baseline status or stabilized or have otherwise been explained. Should an 
AE result in death, a full autopsy 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). 
11.4.1. 
Reporting Serious Adverse Events 
If an AE is serious (as defined in Section 11.1.2), the investigator must submit a SAE report form 
at the time the SAE is identified. All SAEs must 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. Serious adverse event report forms must be faxed to the designated Safety 
Fax number (+ 1 732-289-6060). 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. FAX reporting is preferred, but in case of no 
access to a fax machine, send documentation to the following email address: 
saereporting_pompe@amicusrx.com. 
The initial report must be as complete as possible. All known details of the SAE, and an 
assessment of the causal relationship between the event and ATB200 administered as a single 
agent, the use of ATB200 co-administered with AT2221, 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, results of diagnostic procedures/evaluations related to the event, etc) 

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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 11.1.2) 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.  
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, she/he should contact the Amicus 
Medical Monitor to determine how the SAE should be documented and reported.  
The Amicus Medical Monitor will determine the expectedness of AEs according to current 
safety reference document (eg, current investigator brochure or other safety-related information 
as available). 
11.4.2. 
Additional Reporting Requirements for Suspected Unexpected Serious Adverse 
Reaction  
Any AE that is serious, unexpected, and associated with the use of study treatment (SUSAR, also 
referred to as Expedited Safety Report, Investigational New Drug Safety Report), has additional 
reporting requirements. All investigators conducting clinical trials with the study treatment will 
be notified of such events and must inform their IRBs/ECs as required in accordance with local 
law. Amicus will ensure 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 study treatment, 
and unexpected, regulatory authorities and IRBs/ECs 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 study treatment, and unexpected, regulatory authorities and IRBs/ECs 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/ECs 
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. 
11.4.3. 
Additional Reporting Requirements for Serious Adverse Reaction  
For subjects in this study that participate at more than one study site, Amicus drug safety 
personnel will forward a copy of the initial SAE report to any alternate site(s) attended by the 
subject. When all information related to the SAE is available, a MedWatch form will be sent to 
all sites at which the subject participates. 

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If additional information such as medical history (inclusive of FVC and 6MWT, plasma CK, 
ALT, AST, and urine Hex4 lab results) is obtained from the report or from a hospital discharge 
summary, the data should be reconciled by the primary site (site conducting Functional 
Assessment) and recorded in the eCRF accordingly. 
11.5. 
Study Treatment Interruptions/Discontinuation Due to an Adverse 
Event 
Investigators may choose to discontinue subjects from the study in the case of an AE or for 
administrative reasons. All discontinuations must be documented in the eCRF with the 
appropriate source documents and communicated to the Amicus Medical Monitor immediately.  
If the reason for discontinuation of the study is an abnormal assessment (eg, ECG finding) or a 
laboratory test abnormality, the information must be recorded as an AE in the eCRF and source 
records. 
11.6. 
Other Reporting Situations 
11.6.1. 
Pregnancy 
Pregnancy in and of itself is not regarded as an AE; however, pregnancy information on female 
subjects and female partner of male subjects, participating in this study, is collected by Amicus. 
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, must be reported 
using Amicus’ pregnancy notification form (subject to receipt of any data privacy release 
approvals where required under local privacy laws) within 5 working days of the investigator or 
study staff becoming aware of the pregnancy. If an SAE occurs in conjunction with the 
pregnancy, the same SAE reporting requirements described in Section 11.4.1 apply. Instructions 
regarding collection of pregnancy and outcome information will be provided by Amicus.  
11.6.2. 
Overdose/Underdose 
Any event associated with, or observed in conjunction with, a product overdose/under dose 
(whether accidental or intentional) is considered by Amicus to be an AE and must be reported as 
such. If a subject experiences an overdose (defined as ≥ 20% higher than the assigned dose of 
study treatment for that period in the protocol) or an underdose (defined as ≥ 20% lower than the 
assigned dose of study treatment for that period in the protocol) during the course of the study 
(whether symptomatic or not), Amicus Medical Monitor must be notified within 5 working days 
of the investigator or study staff first becoming aware of the overdose. Follow-up information 
must be forwarded on the outcome as applicable. If an SAE occurs in conjunction with the 
overdose, the same SAE reporting requirements described in Section 11.4.1 apply. 
If a subject is unable to schedule a treatment (infusion) up to 7 days after the actual scheduled 
date, this is considered as a missed dose. The subject will receive the next dose per his/her 
schedule. In this case, the interval between 2 doses will be approximately 4 weeks. This is 
recorded as a protocol deviation and an adverse event. Amicus Medical Monitor must be notified 
within 5 working days of the investigator or study personnel first becoming aware of the missed 
dose. Follow-up information must be forwarded on the outcome as applicable. If an SAE occurs 

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in conjunction with the underdose, the same SAE reporting requirements described in 
Section 11.4.1 apply. 

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12. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
This section outlines the planned statistical analyses. Further details of the data handling rule and 
statistical calculations will be provided in a separate statistical analysis plan (SAP).  
12.1. 
Endpoints 
12.1.1. 
Primary Endpoints 
Safety: 
• Identification and counts of TEAEs, treatment-emergent SAEs, including IARs 
• Changes from baseline in 12-lead ECG  
• Changes from baseline in clinical safety laboratory evaluations: serum chemistry, 
hematology, and urinalysis  
• Changes from baseline in PEs 
• Changes from baseline in vital signs 
• Changes from baseline in serum CK 
PK for subjects from Cohort 1: 
• Plasma GAA activity levels and total GAA protein concentration PK parameters: 
Cmax, tmax, AUC0-t, AUC0-∞, t½, steady state volume of distribution (Vss), and CLT for 
each dose level 
• Stage 1: Ratios of plasma GAA activity levels and total GAA protein concentration 
Cmax, AUC0-t, and AUC0-∞ for 20 mg/kg versus 5 mg/kg, 20 mg/kg versus 10 mg/kg, 
and 10 mg/kg versus 5 mg/kg 
• Stage 2: Ratios of plasma GAA activity levels and total GAA protein concentration 
Cmax, AUC0-t, and AUC0-∞ for 20 mg/kg ATB200 (from Stage 1) versus single-dose 
20 mg/kg ATB200 + 130 mg AT2221, and versus single-dose 20 mg/kg ATB200 + 
260 mg AT2221  
• Stage 2: Ratios of plasma GAA activity levels and total GAA protein concentration 
Cmax, AUC0-t, and AUC0-∞ for 20 mg/kg ATB200 + 130 mg AT2221 single-dose 
versus multiple-dose, and 20 mg/kg ATB200 + 260 mg AT2221 single-dose versus 
multiple-dose 
• Plasma AT2221 PK parameters: Cmax, tmax, AUC0-t, AUC0-∞, t½, total clearance 
following oral administration (CLT/F), and terminal phase volume of distribution 
following oral administration (Vz/F) for each dose level 
• Ratios of plasma AT2221 Cmax, AUC0-t, and AUC0-∞ for 260 mg single-dose versus 
130 mg single-dose, and for 260 mg multiple-dose versus 130 mg multiple-dose 
• Ratios of plasma AT2221 Cmax, AUC0-t, and AUC0-∞ for 130 mg multiple-dose versus 
130 mg single-dose, and 260 mg multiple-dose versus 260 mg single-dose 

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12.1.2. 
Secondary Endpoints 
Functional: 
• For ambulatory subjects: change and percent change from Baseline in Gower’s 
Maneuver, 4-stair-climb, 6MWT, 10-Meter Walk Test (10MWT), GSGC score, TUG, 
muscle strength tests (MRC and hand-held dynamometer [for both upper and lower 
limbs]), and pulmonary function tests (FVC, MIP, MEP, and SNIP [for subjects 
without invasive ventilatory support]) 
• For nonambulatory subjects: change and percent change from Baseline in muscle 
strength tests (MRC and hand-held dynamometer [upper limbs only]) and pulmonary 
function tests (FVC, MIP, MEP, and SNIP [for subjects without invasive ventilatory 
support]) 
Patient-reported Outcomes: 
• Change and percent change from Baseline in FSS, RHS, and R-PAct Scale 
Global Impression of Change: 
• PGIC and SGIC 
PK parameters for subjects from Cohorts 1 and 3: 
• Plasma GAA activity levels and total GAA protein concentration PK parameters: 
Cmax, tmax, AUC0-t, AUC0-∞, t½, CLT and Vss 
• Plasma GAA activity levels and total GAA protein concentration ratios for Cmax, 
AUC0-t, and AUC0-∞ for single-dose versus multiple-dose 
• Plasma AT2221 PK parameters: Cmax, tmax, AUC0-t, AUC0-∞, t½, CLT/F, and Vz/F 
• Plasma AT2221 Cmax, AUC0-t, and AUC0-∞ ratios for single-dose versus multiple-dose 
• Single-dose plasma GAA activity levels, total protein concentration and AT2221 
Cmax, AUC0-t, and AUC0-∞ ratios for subjects from Cohort 3 versus subjects from 
Cohort 1 following 20 mg/kg ATB200 alone, 20 mg/kg ATB200 + 130 mg AT2221 
single-dose, and 20 mg/kg ATB200 + 260 mg AT2221 single-dose 
12.1.3. 
Exploratory Endpoints 
• Anti-rhGAA antibodies (total and neutralizing)  
• Cross-reactivity of anti-rhGAA antibodies to alglucosidase alfa  
• Pro-inflammatory cytokines and other biomarkers of immune system activation 
• PD biomarkers: urinary Hex4 and serum CK  
• Evaluation of anti-rhGAA antibody impact on AUC and CLT after at least 18 months 
of ATB200/AT2221 treatment as compared to AUC and CLT after the first and third 
doses of 20 mg/kg ATB200 + 260 mg AT2221  

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12.2. 
Hypotheses 
No formal statistical hypotheses are specified for this study. 
12.3. 
Sample Size Considerations 
No formal sample size calculation was performed. The sample size between 18 to 34 subjects is 
considered adequate for the purpose of this study. 
12.4. 
Data Analysis Considerations 
12.4.1. 
Analysis Populations 
• Safety Population: this includes all enrolled subjects who have been exposed to at 
least 1 dose of study treatment (ATB200 and/or AT2221). 
− The Safety population will be used in the analysis of all safety parameters 
(including AEs, vital signs, laboratory assessments, and biomarkers). 
• PK Analysis Population: includes enrolled subjects who have been exposed to at least 
1 dose of study treatment (ATB200 and/or AT2221) and have completed at least 1 PK 
period. 
− The PK population will be used for PK analyses. 
• Intent-to-Treat Population: includes all enrolled subjects. 
• Other populations may be defined in the SAP. 
12.4.2. 
Interim Analyses 
Interim analyses will be performed in the study as needed. Full details for the interim analysis 
will be presented in the SAP. 
12.4.3. 
PK/PD Analysis 
12.4.3.1. Drug Concentration Data 
Blood samples will be collected at serial time points specified in Table 14 for plasma GAA 
activity, plasma total GAA protein concentration, and plasma AT2221 concentration for all 
subjects. Plasma GAA activity levels, total GAA protein, and AT2221 concentrations will be 
used to compute PK parameters defined in Section 12.4.3.2.  
12.4.3.2. PK Parameters 
Plasma PK parameters will be computed by noncompartmental analysis with Phoenix® 
WinNonlin® version 6.4. For the purpose of calculating PK parameters, values below the limit of 
quantification (BLQ) will be set to 0 when a BLQ occurs before the first measurable 
concentration. If a BLQ occurs after a measurable concentration in a profile and is followed by a 
value above the lower limit of quantification, then the BLQ will be treated as “missing”. If a 
BLQ value occurs at the end of the blood sampling interval (after the last quantifiable 
concentration) it will also be treated as “missing”. For descriptive statistics of plasma activity 

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and concentration data, all BLQs will be set to 0 and included in designated statistical 
calculations. PK analyses performed on preliminary quality checked activity or concentration 
data will use nominal time points. PK analyses performed on final activity or concentration data 
will use actual time points. PK endpoints may include the following: 
Plasma GAA activity levels and total GAA protein concentration PK parameters will be 
calculated as follows:  
• Cmax: Maximum observed activity level or concentration obtained directly from the 
activity or concentration profile 
• tmax: Time of the first occurrence of the maximum observed activity level or 
concentration obtained directly from the activity or concentration profile 
• Kel or λz: The apparent terminal phase elimination rate constant will be estimated by 
linear regression of logarithmically transformed concentration (or activity) versus 
time data. Only those data points which are judged to describe the terminal log-linear 
decline will be used in the regression. 
• AUC0-t: The area under the plasma drug concentration-time curve from 0 time 
(predose) to the time of last quantifiable concentration (t) will be calculated with the 
linear up/log-down trapezoidal method 
• AUC0-∞: The area under the plasma drug concentration-time curve from 0 time 
(predose) extrapolated to infinite time will be calculated as follows: 
AUC0-∞ = AUC0-t + Ct/+λz 
Where Ct is the last observed quantifiable concentration 
• t½β: The beta-phase terminal elimination half-life, calculated as natural log (ln)[2]/λz 
from the last 3 or more quantifiable concentrations from the beta phase of elimination 
• t½α: The alpha-phase terminal half-life, calculated as ln(2) / λz from the first 3 or more 
quantifiable concentrations after Cmax. Estimated for plasma GAA activity levels and 
total GAA protein concentration only 
• CLT: total plasma clearance after IV administration, calculated as Dose/AUC0-∞  
• Vss: Steady-state volume of distribution from an IV administration, calculated as 
Dose•AUMC/(AUC)2, where AUMC is area under the first moment curve 
Plasma AT2221 PK parameters will include the parameters listed above in addition to the 
following:  
• CLT/F: Total plasma clearance from an oral administration, calculated as 
Dose/AUC0-∞ 
• Vz/F: Volume of distribution based on the terminal elimination phase from an oral 
administration, calculated as Dose/(AUC0-∞ ∙λz) 

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12.4.4. 
Statistical Methods 
12.4.4.1. Statistical Plan for PK Data  
For the purpose of summarizing drug concentration/activity data, all BLQs will be set to 
zero (0) values. Drug concentration/activity data will be summarized with descriptive statistics 
including arithmetic means, standard deviations (SDs), coefficients of variation, median, 
minimum, and maximum, standard error of the mean, and 5th and 95th percentiles. 
Pharmacokinetic parameters will be summarized with descriptive statistics including N (number 
of subjects in the treatment population), arithmetic means, SDs, coefficients of variation, median, 
minimum, and maximum. Geometric means will be calculated for AUC0-t, AUC0-∞, and Cmax.  
The following statistical analysis of variance (ANOVA) comparisons will be performed to assess 
the relative bioavailability on PK parameters Cmax, AUCt-0, and AUC0-∞ for plasma GAA activity 
levels and total GAA protein concentrations:  
Cohort 1 Subjects: 
• 20 mg/kg ATB200 + 130 mg AT2221 (single dose) versus 20 mg/kg ATB200 alone 
• 20 mg/kg ATB200 + 260 mg AT2221 (single dose) versus 20 mg/kg ATB200 alone 
• 20 mg/kg ATB200 + 130 mg AT2221 (single dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (single dose) 
• 20 mg/kg ATB200 + 130 mg AT2221 (multiple dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (multiple dose) 
• 20 mg/kg ATB200 + 130 mg AT2221 (single dose) versus 20 mg/kg ATB200 + 
130 mg AT2221 (multiple dose) 
• 20 mg/kg ATB200 + 260 mg AT2221 (single dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (multiple dose) 
Cohort 3 Subjects: 
• 20 mg/kg ATB200 + 260 mg AT2221 (single dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (multiple dose) 
Cohort 3 versus Cohort 1 Subjects: 
• 20 mg/kg ATB200 + 260 mg AT2221 (multiple dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (multiple dose) 
• 20 mg/kg ATB200 + 260 mg AT2221 (single dose) versus 20 mg/kg ATB200 + 
260 mg AT2221 (single dose) 
• 20 mg/kg ATB200 + 260 mg AT2221 (multiple dose) versus 20 mg/kg ATB200 
alone 
• 20 mg/kg ATB200 + 260 mg AT2221 (single dose) versus 20 mg/kg ATB200 alone 
Following ln-transformation, plasma GAA activity levels and total GAA protein concentration 
Cmax, AUC0-∞, and AUC0-t, will be separately analyzed using a fixed effects model with fixed 
effect terms for treatment or subject group. Point estimates, and their associated 90% confidence 

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intervals (CIs) will be constructed for the differences, test treatment or subject group, and 
reference treatment or subject group. The point estimates and their associated 90% CIs will then 
be back-transformed to provide point estimates and 2-sided 90% CIs for the ratios of 
test/reference, on the original scale. 
A dose proportionality assessment will be performed using the power method for 5, 10, and 
20 mg/kg ATB200 in Stage 1 and for 130 and 260 mg AT2221 in Stage 2. 
For the dose proportionality analysis, in Stage 1, the reference treatment will be 5 mg/kg 
ATB200, and the test treatments will be 10 mg/kg and 20 mg/kg ATB200 and, in Stage 2, the 
reference treatment will be 130 mg AT2221, and the test treatment will be 260 mg AT2221. For 
the ANOVA comparisons within Stage 2, the reference treatments will be single-dose, and the 
test treatments will be multiple-dose, and between Stages 1 and 2, the reference treatment will be 
20 mg/kg ATB200 alone, and the test treatments will be 20 mg/kg ATB200 + 130 mg AT2221 
and 20 mg/kg ATB200 + 260 mg AT2221. For between subject comparisons, the reference 
group will be Cohort 1 subjects, and test group will be Cohort 3 subjects. 
For effect of anti-rhGAA antibody on total GAA protein exposures and plasma clearance, 
statistical comparisons between after at least 18 months of treatment in Stage 3 versus the first 
and third doses of treatment with 20 mg/kg ATB200 + 260 mg AT2221 will be performed on 
estimated plasma total GAA protein AUCs, plasma clearance, and 4-, 6-, 8-, and 12-hour plasma 
total GAA protein concentrations. PK data from both cohorts will be pooled for the statistical 
comparisons.  
12.4.4.2. Efficacy Analyses 
Details of the analysis methodology for all non-PK endpoints will be provided in the main SAP 
for the study. 
In general, descriptive statistics will be provided for all efficacy endpoints. Continuous variables 
will be summarized using the number of observations (n), mean, standard deviation, median, 
minimum, and maximum, while categorical variables will be summarized using frequency and 
percentages. The absolute and percent changes from baseline for the continuous efficacy 
variables will be similarly summarized.  
Each cohort will have its own baseline, and analysis will be performed by cohort and overall. In 
addition, summary analyses will be performed by combining Cohort 1, 3, and 4 for ambulatory 
subjects, or by combining Cohort 1 and 4 for ERT-experienced subjects. For Cohort 1, the 
analysis will also be provided by treatment dosing regimen. The visit values and the change from 
baseline to the post-baseline assessment will be analyzed by scheduled visit. The 95% CI (for the 
mean change from baseline and/or median difference) by scheduled visit will be provided for 
summary purposes only. 
12.4.4.3. Safety Analyses 
Adverse events and concomitant medications terms will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA) version 16.1 or higher and WHO Drug Dictionary.  
In general, TEAEs will be grouped by MedDRA System Organ Classes and by Preferred Terms. 
Summary statistics will be provided by cohort for AEs, ECG shift changes, vital signs shift 
changes, and clinical laboratory shift data based on the potentially CS values defined in 

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Appendix 2. In addition, summary statistics (n, mean, median, SD, minimum, and maximum) 
will be provided for values at each visit and changes from baseline at each visit for ECG, vital 
signs, and clinical laboratory assessments by cohort. 
Prior and concomitant medications will also be summarized by cohort. A by-subject listing of 
protocol deviations will be provided. 
12.4.4.4. Immunological Analyses  
The effect of immunogenicity results on PK, PD, efficacy, and safety will be explored. Further 
details will be provided in the SAP. Assessments may include the following:  
• Baseline anti-rhGAA antibody-positive (total and neutralizing) subjects as a 
percentage of the total number of subjects whose baseline samples were tested for 
anti-rhGAA antibodies 
• Antibody range (median and interquartile range [IQR]) of the baseline anti-rhGAA 
antibody-positive samples (total and neutralizing) 
• Percentage of baseline anti-drug antibody-positive subjects with significant increases 
in anti-rhGAA antibodies (total and neutralizing) after biologic drug administration 
(ie, when any one sample taken after the initial drug administration has an 
anti-rhGAA titer that is greater than the baseline titer by a scientifically reasonable 
margin) 
• anti-rhGAA antibody-positive subjects at every visit as a percentage of the total 
number of subjects whose baseline samples were tested for anti-rhGAA (total and 
neutralizing) 
• anti-rhGAA antibody-positive subjects at every visit as a percentage of the total 
number of subjects whose samples were tested at that visit for anti-rhGAA (total and 
neutralizing) 
• Antibody range (median and IQR) of the anti-rhGAA antibody-positive samples at 
every visit (total and neutralizing) 
• Kinetics and duration of anti-rhGAA antibodies over time in the study (total and 
neutralizing) 
• Evaluation of high, mid, low, or no antibody groups (total and neutralizing) on 
plasma GAA activity levels and total GAA protein concentration Cmax AUC, and CL 
over time in the study 
• Evaluation of high, mid, low, or no antibody (total and neutralizing) groups on 
PD assessments (Hex4 and CK) over time in the study 
• Cytokine levels and changes over time in the study  
12.4.4.5. Baseline Demographic and Subject Characteristics 
Baseline demographics and subject characteristics will be presented for all subjects included in 
the statistical analysis. Analyses will also be performed separately for subjects in Cohorts 1, 2, 3, 
and 4. 

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Functional assessments at baseline will be summarized for all subjects and will include the 
following: 
• For subjects in Cohorts 1, 3, and 4: Motor function tests (Gower’s Maneuver, 6MWT, 
10MWT, GSGC, TUG, 4-stair climb), muscle strength tests (MRC and hand-held 
dynamometer [for both upper and lower limbs]), and PFTs (FVC, MIP, MEP, and 
SNIP) 
• For subjects in Cohort 2: muscle strength tests (MRC and hand-held dynamometer 
[upper limbs only]) and PFTs (FVC, MIP, MEP, and SNIP [in subjects with 
noninvasive ventilatory support only]) 
• For all cohorts: PROs (FSS, RHS, and R-PAct Scale) 
12.4.4.6. Subject Disposition 
A summary table will be provided for subjects enrolled, included in all statistical analyses, 
completed each visit, discontinued the study, and reasons for discontinuation. 

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13. 
STUDY TREATMENTS 
13.1. 
Description of Study Treatments 
ATB200 (recombinant human acid α-glucosidase [rhGAA]) functions as ERT. 
AT2221 (N-butyldeoxynojirimycin) is an iminosugar that functions as a selective 
pharmacological chaperone of GAA or rhGAA.  
Table 20: 
Investigational Product 
 
Investigational Product 
Product Name 
ATB200 
AT2221 
Dosage Form 
lyophilized powder for 
intravenous infusion 
hard gelatin capsule 
Unit Dose 
15 mg/mL 
65 mg 
Route of Administration 
intravenous 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  
Manufacturer 
WuXi AppTec 
Biopharmaceuticals Co., Ltd 
108 Meiliang Road 
Mashan, Binhu District, 
WuXi, China 
AAI Pharma 
1726 N. 23rd Street 
Wilmington, NC 28405 
USA 
13.2. 
Packaging and Labeling 
AT2221 (65 mg) will be supplied by Amicus as hard gelatin capsules in plastic bottles and will 
be administered orally. 
ATB200 (105 mg/vial) will be supplied by Amicus 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. 
Each container will be labeled in conformance to 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. 
13.3. 
Study Treatment Administration 
13.3.1. 
ATB200 
The doses of ATB200 are either 5, 10, or 20 mg/kg body weight.  

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ATB200 does not contain any preservatives. Vials are single-use only. Reconstituted vials should 
be retained at the site until the study monitor checks accountability. 
In all stages, ATB200 is to be administered every 2 weeks as an approximate 4-hour IV infusion 
(± 15 minutes). Changes in the duration of ATB200 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. Intravenous administration of ATB200 (during all stages) should be 
performed by qualified study personnel. Any delegation of this responsibility must follow 
Section 15.4. Rate and duration of infusion must be constant for each infusion. Changes in the 
rate and/or duration of infusion due to safety or tolerability issues will be documented. 
13.3.2. 
AT2221 
The doses of AT2221 are either 130 mg or 260 mg administered orally, approximately 1 hour 
before ATB200 infusion. For a 130 mg dose, take 2 capsules. For a 260 mg dose, take 
4 capsules. 
At each visit in Stage 2, the administration of AT2221 oral capsule(s) 1 hour before the IV 
infusion of ATB200 should be supervised by the investigator or a qualified designee. Subjects 
should fast for at least 2 hours before and 2 hours after administration of AT2221. 
13.4. 
Study Treatment Accountability 
In accordance with local regulatory requirements, the investigator, designated site staff, or head 
of the medical institution (where applicable) must document the amount of investigational 
product dispensed and/or administered to study subjects, the amount returned by study subjects, 
and the amount received from and returned to Amicus (or designee), when applicable. Product 
accountability records must be maintained throughout the course of the study. 
13.5. 
Handling, Storage, Return, and Disposal of Study Treatment 
Sites will be instructed to store AT2221 65 mg oral capsules according to the conditions 
identified on the labels of each study treatment, at room temperature (15°C to 25°C/59°F to 
77°F) with excursions permitted to (30°C/86°F) in a secure area, free from environmental 
extremes, and with restricted access.  
Sites will be instructed to store ATB200 lyophilized powder vials according to the conditions 
identified on the label, at cold temperature (2°C to 8°C/36°F to 46°F) with short excursions 
permitted to (25°C/77°F) in a secure area, free from environmental extremes, and with restricted 
access. 
A temperature log must be maintained for the duration of the study, and the temperature of the 
storage room (or cabinet) in which study treatment is stored must be recorded for each working 
day of the week that pharmacy staff (or designated study staff) is available. Temperature is 
required to be recorded using a standard Min-Max thermometer that has calibration records 
available (details usually contained within the device leaflet) and is maintained according to 
institutions standard maintenance policy. 

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Study treatment is to be stored only at the site(s) listed on the Form FDA 1572. Study treatment 
is to be dispensed only to subjects who have provided written informed consent, have met all 
entry criteria, and are assigned subject numbers. 
The investigator, or appropriately assigned designee, will inventory and acknowledge receipt of 
all shipments of study treatments. The investigator must keep an accurate record/log of the 
quantities of study treatment dispensed and administered to each subject. The study monitor will 
periodically check the supplies of study treatment s held at the site to verify accountability of all 
study treatment s used and to verify the study treatment accountability logs are completed and 
maintained in the investigator study file. When instructed by the study monitor, the investigator 
will return all original containers of study treatments, whether empty, or containing used or 
unused study treatments to Amicus or their designee for destruction. Sites may not destroy study 
treatments on site unless Amicus has provided prior written approval. 

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14. 
STUDY MANAGEMENT 
14.1. 
Documentation of Protocol-required Information and Study 
Findings 
14.1.1. 
Electronic Case Report Form Completion 
This protocol will use eCRFs with remote electronic data capture provided through a qualified 
third party vendor. The data will be entered on the eCRFs in a timely manner on an ongoing 
basis as defined in the Data Management Plan. The investigator, or designated representative, 
should complete the eCRF pages as soon as possible after information is collected, preferably on 
the same day that the subject is seen for an examination, treatment, or any other study procedure. 
Any outstanding entries must be completed immediately after the final examination. An 
explanation should be given for all missing data. 
Details of eCRFs completion and correction will be explained to the investigator. The 
investigator is responsible for ensuring that data are properly recorded on each subjects eCRFs 
and related documents. If the investigator authorizes other persons to make entries into the eCRF 
pages, the names, positions, signatures, and initials of these persons must be supplied to Amicus. 
The completed eCRF must be reviewed and electronically signed by the investigator who signed 
the study protocol signature page to ensure that the observations and findings are recorded on the 
eCRFs correctly and completely. 
At the end of the study, eCRFs (including queries and audit trails) will be retained by Amicus 
and copies will be sent to the investigator to maintain as the investigator’s copy. 
14.2. 
Data Management 
Only data specified in the protocol will be collected as part of this study. All eCRF data will be 
entered into the Electronic Data Capture (EDC) system managed by the contract research 
organization (CRO). Additional protocol specified data, such as laboratory and ECG data, may 
be collected through third party vendors and integrated with eCRF data by the CRO to create 
complete datasets for analysis. All protocol-specified data will be transmitted electronically to 
Amicus (or the CRO). 
Management of clinical data will be performed in accordance with applicable Amicus standards 
and data cleaning procedures as defined in the Data Management Plan to ensure the integrity of 
the data (eg, determining errors and inconsistencies in the data, and ensuring data are corrected 
by site personnel or designees). Adverse events and concomitant medications terms will be 
coded using MedDRA version 16.1 or higher and WHOMD. 
After database lock, each site will receive a compact disc (CD) containing all of their 
site-specific eCRF data as entered into the EDC system for the study, including full discrepancy 
and audit history. Additionally, a CD copy of all of the study center’s data from the study will be 
retained by Amicus or designee for storage. 

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14.3. 
Safety Steering Committee (SSC) 
An SSC is a committee consisting of medical experts from Amicus (the Amicus Medical 
Monitor), study investigators, and additional medical experts (as needed) formed to evaluate the 
safety data from sentinel dosing. Subsequent dosing in the study will proceed if the SSC 
identifies no significant safety issues or concerns that would preclude further treatment and 
assesses ATB200 co-administered with AT2221 sentinel dose as safe and well tolerated. 
The formation and use of an SSC will be determined prior to the beginning of this study, or if, 
during the study, deemed necessary by Amicus. Specific details pertaining to the membership, 
roles, responsibilities, and procedures of the SSC will be documented in the SSC Charter. An 
SSC Charter will include operational and logistical procedures for the SSC. 
14.4. 
Study Monitoring, Source Data Verification, and Onsite Audits 
Monitoring and auditing procedures developed or endorsed by Amicus will be followed, in 
compliance with Good Clinical Practice (GCP) guidelines. Direct access to the onsite study 
documentation and medical records must be ensured by the investigator. 
Monitoring will be done by personal visits from an Amicus representative (ie, study monitor) 
who will check the eCRFs for completeness and clarity, and crosscheck them with source 
documents. In addition to the monitoring visits, frequent communications (eg, letter, e-mail, 
telephone, and fax) by the study monitor will ensure that the study is conducted according to the 
protocol design and regulatory requirements. 
Domestic and foreign regulatory authorities, the IEC/IRB, an auditor authorized by Amicus may 
request access to all source documents, eCRFs, and other study-related documentations for onsite 
audit or inspection. Direct access to these documents must be guaranteed by the investigator, 
who must provide support at all times for these activities. Medical records and other study 
documents may be copied during audit or inspection provided that the subject names are 
obliterated on the copies to ensure confidentiality. 
The investigator should contact Amicus immediately if contacted by a regulatory authority 
regarding an inspection or audit. 
14.5. 
Records Retention 
The investigator must obtain approval in writing from Amicus before destruction of any records. 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an International Conference on Harmonisation (ICH) region and until 
there are no pending or contemplated marketing applications in an ICH region, or at least 2 years 
have elapsed since the formal discontinuation of clinical development of ATB200 administered 
as a single agent and co-administered with AT2221. However, because of international 
regulatory requirements or country-specific requirements, Amicus may request retention for a 
longer period. 
Prior to any decision regarding the disposal or destruction of study documents, the investigator 
should contact Amicus. Amicus may request that the site take alternative actions other than 
disposal or destruction of study documents. 

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Essential documents include: 
• signed informed consent documents for all subjects 
• subject identification code list∗, screening log (if applicable), and enrollment log 
• composition of the IEC/IRB (or other applicable statement) and record of all 
communications between the investigator and IEC/IRB as well as between the 
investigator and Amicus or CRO 
• list of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study and their signatures 
• copies of eCRFs and documentation of corrections for all subjects 
• investigational product accountability records 
• record of any body fluids or tissue samples retained 
• all other source documents (eg, subject medical records, hospital records, laboratory 
records, etc) 
• all other documents as listed in Section 8 of the ICH GCP E6 guidelines (ie, Essential 
Documents for the Conduct of a Clinical Trial) 
Normally, these records will be held in the investigator's archives. If the investigator is unable to 
meet this obligation, he or she must ask Amicus for permission to make alternative 
arrangements. Details of these arrangements must be documented. 
14.6. 
Use of Study Findings 
All information concerning ATB200 administered as a single agent and co-administered with 
oral AT2221 as well as any matter concerning the operation of Amicus, such as clinical 
indications for ATB200 administered as a single agent and co-administered with oral AT2221, 
its formula, methods of manufacture, and other scientific data relating to it, that have been 
provided by Amicus and are unpublished, are confidential, and must remain the sole property of 
Amicus. The investigator will agree to use the information only for the purpose 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. 
                                                 
∗EU legislation requires this list to be maintained for a minimum of 15 years. 

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Amicus will ensure that a final report on the study is prepared. Amicus will ensure that the study 
findings are reported in a manner that complies with applicable requirements for reporting 
clinical study results. 
As required by local regulation or by the IEC/IRB, a summary of the study will be submitted by 
Amicus to the regulatory authorities and by the investigator to the IEC/IRB. 
14.7. 
Study Close-out  
The end of study is defined as date of database lock. 
The study must be closed at the site on completion. Study close-out will be performed by the 
study monitor upon closure of the study. 
Completion or premature termination of the study will be reported by Amicus to the regulatory 
agency and by Amicus or by the investigator to the IEC/IRB as required by local regulation or by 
the IEC/IRB. 
Furthermore, Amicus or the investigator has the right to close any study site at any time. As 
much as possible, premature closure would occur after mutual consultation. 
Study materials must be returned, disposed of, or retained as directed by Amicus (Section 13.5 
and Section 14.5). 

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15. 
STUDY CONDUCT CONSIDERATIONS 
This global study will include both Investigational New Drug (IND) (US) and non-IND (foreign) 
sites. All investigators will be required to certify their compliance with both ICH E6 GCP and 
their respective country’s applicable laws and regulations. Both IND and non-IND sites will be 
operating under a single protocol (ie, there will not be a separate protocol for non-IND sites). 
The sponsor will ensure 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. 
15.1. 
Posting of Information on Publicly Available Clinical Trial Registers 
Amicus will be responsible for registering this study in a public registry that meets the 
requirements specified by the International Council of Medical Journal Editors, such as 
www.clinicaltrials.gov. 
15.2. 
Ethical and Legal Aspects 
15.2.1. 
Subject Information and Informed Consent  
Signed written informed consent is to be obtained from each subject prior to enrollment into the 
study. The document must be in a language understandable to the subject and must specify who 
informed the subject. Where required by local law, the person who informs the subject must be a 
physician. 
The subject (subject’s legally authorized representative) must be given the opportunity to read 
the informed consent document and have all their questions and concerns addressed before 
giving consent in writing. If the subject or subject’s legally authorized subject representative is 
unable to read, oral presentation and explanation of the written informed consent form 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 or by a local legally-recognized alternative (eg, the 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. 
The subject's consent must be confirmed at the time of consent by the personally dated signature 
(or thumbprint or mark) of the subject or subject’s legally authorized representative or guardian 
and by the personally-dated signature of the person conducting the informed consent discussions. 
A copy of the signed informed consent 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 informed consent. 
The witness and the person conducting the informed consent discussions must also sign and 
personally date the consent document. Until a signed written consent has been obtained, the 
investigator will not undertake any measures specifically required for this study. 

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The investigator may inform the subject’s primary physician about the subject’s participation in 
the study if the subject has a primary physician and if the subject agrees to the primary physician 
being informed. 
15.2.2. 
Ongoing Information for IEC/IRB  
The information listed below must be submitted to IECs/IRBs according to timelines specified 
by individual IEC/IRB documented submission policies and procedures, or by local law. 
Submissions may be made by Amicus (or designee) or by the investigator. The parties 
responsible for submissions will be identified and documented prior to shipment of study 
treatments. 
• AE information 
• expedited safety reports 
• periodic reports on the progress of the study 
15.2.3. 
Compliance With Good Clinical Practice (GCP) 
This study is to be conducted according to globally accepted standards of GCP (as defined in the 
ICH GCP E6 guidelines), in agreement with the current version of Declaration of Helsinki, and 
in keeping with local regulations. 
15.2.3.1. Quality Control  
In accordance with applicable regulations, GCP, and Amicus’ procedures, Amicus or its 
designee will contact the site prior to the start of the study to review with the study staff 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. 
Amicus or its designee will monitor the study to ensure: 
• data are authentic, accurate, and complete 
• safety and rights of subjects are being protected 
• study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements 
The investigator and the head of the medical institution (where applicable) agrees to allow the 
monitor direct access to all relevant documents. 
15.2.3.2. 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 medical institution) must 
agree to grant the advisor(s), auditor(s), and inspector(s) direct access to all relevant documents 
and to allocate their time and the time of their staff to discuss the conduct of the study, any 

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findings/relevant issues, and to implement any corrective and/or preventative actions to address 
any findings/issues identified during the regulatory audit or inspection. 
15.2.4. 
Subject Data Protection 
Subject names will not be supplied to Amicus. A unique subject number will be recorded in the 
case report form, and if the subject name appears on any other document (eg, laboratory report), 
it must be obliterated on the copy of the document to be supplied to Amicus. Study findings 
stored on a computer will be stored in accordance with local data protection laws (eg, European 
Union [EU] Directive 95/46/EC, EU Directive 94/45/EC, and the General Data Protection 
Regulation (GDPR) (EU) 2016/679]). The subject will be informed that representatives of 
Amicus, IEC/IRB, or regulatory authorities may inspect their medical records to verify the 
information collected, and that all personal information made available for inspection will be 
handled in strictest confidence and in accordance with local data protection laws. 
The investigator will maintain a personal subject identification list (subject numbers with the 
corresponding subject names) to enable records to be identified. 
15.3. 
Clinical Study Protocols and Amendments 
Any nonadministrative changes to the protocol, initiated either by Amicus or by the investigator, 
will require a formal amendment procedure. Approval of all amendments must be obtained from 
Amicus, relevant IEC/IRB, and regulatory authorities (in accordance with local requirements) 
prior to implementation. Changes to the administrative aspects of the study will not require 
formal protocol amendments or IEC/IRB approval, but can be treated as administrative 
amendments. However, the IEC/IRB should be kept informed of such changes. Changes in study 
staffing or contact information are examples of administrative changes not requiring formal 
protocol amendments. 
Protocol deviations to eligibility criteria, addition or deletion of tests, dosing, duration of 
treatment, and/or any other aspect of the study design that may significantly impact subject 
safety or scientific integrity, are not permitted under GCP or by Amicus, unless necessary to 
eliminate an immediate hazard to the subject(s). 
Where Amicus and/or investigator must take urgent safety measures to protect the subjects from 
an immediate hazard, a protocol deviation may be allowed prior to obtaining approval from the 
relevant IEC/IRB (and/or regulatory authorities) according to 21 Code of Federal Regulations 
(CFR) 312.30(b) (2). In such cases, Amicus and IEC/IRB must be notified within 1 business day. 
Amicus and the relevant IEC/IRB, where required by local law, must be informed of all protocol 
deviations and violations, and the investigators shall document such protocol deviations and 
violations in subject source document and eCRF. 
15.4. 
Delegation of Investigator Duties 
The investigator should ensure that all persons assisting with this study are adequately qualified; 
informed about their study-related duties and functions, the protocol and any amendments to the 
protocol, and the study treatment. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she delegates significant study-related duties. 

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Should the investigator delegate the supervision of the administration of study treatment to a 
designated person, the designee should have the appropriate medical qualifications to effectively 
conduct or supervise any potential resuscitation procedures. 
15.5. 
Liability and Insurance 
Liability and insurance provisions for this study are given in separate agreements. 
15.6. 
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, ATB200 and AT2221, 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, or Amicus on behalf of the investigator, will also 
disclose these financial interests to the IEC/IRB and the investigator will disclose his/her 
financial interests to the subjects in the informed consent information. 
Where required by regulation, Amicus or investigator will also submit the financial arrangements 
for the study to the regulatory authorities or to the IEC/IRB. 
Financial disclosures will be provided by each sub-investigator to whom the investigator 
delegates significant study-related responsibilities. 
15.7. 
Protocol Adherence 
Adherence to the protocol is required. Any significant changes to the clinical trial will be 
incorporated into a protocol amendment and submitted to the IEC/IRB (and, where applicable, 
regulatory authorities) for approval before implementation of the change(s). 
Protocol deviations to inclusion/exclusion criteria, addition or deletion of tests, dosing and/or 
duration of treatment, or any other aspect of the study design that may significantly impact 
subject safety or erode data/scientific integrity, are not permitted under GCP or by Amicus 
unless necessary to eliminate an immediate hazard to the subject (or subjects). Where Amicus 
and/or investigator must take urgent safety measures to protect subjects from an immediate 
hazard, a protocol deviation may be allowed before obtaining approval from the relevant 
IEC/IRB (and/or regulatory authorities). In such cases, the IEC/IRB (and/or regulatory 
authorities) shall be notified of the need for the urgent protocol deviation, the measures taken, 
and the plan for further action. In all cases, reporting to IEC/IRBs and regulatory authorities will 
comply with applicable local requirements. 
Amicus and IEC/IRB must be informed of protocol violations and the investigators shall 
document such protocol violations in subject source records and case report forms. 

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16. 
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Zavesca Package Insert (2008). miglustat capsules, 100mg. South San Francisco, CA, Actelion 
Pharmaceuticals US Inc. 
Zavesca Prescribing Information (2014). miglustat. South San Francisco, CA, Actelion 
Pharmaceuticals US, Inc. 

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APPENDIX 1. SAMPSON CRITERIA FOR ANAPHYLAXIS  
 
Source: Sampson, Muñoz-Furlong et al. 2006  

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APPENDIX 2. POTENTIALLY CLINICALLY SIGNIFICANT 
GUIDELINES 
Criteria for identifying abnormalities as potentially CS are based on the Guidelines for the 
Division of Neuropharmacological Drug Products, US Food and Drug Administration (revised 
on April 2, 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 
which are known to be elevated in some adults with Pompe disease (eg, AST, ALT, LDH) and 
safety laboratory analytes which are not listed below will be reviewed to determine if they are to 
be noted as potentially CS based on the magnitude of the out of range value as compared to the 
normal range and the subject’s baseline value, and whether the out of range value is coded as 
CS 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 
a Reference value: baseline or initial visit value, as appropriate. 

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APPENDIX 3. RASCH-BUILT POMPE-SPECIFIC ACTIVITY (R-PACT) 
SCALE 
 

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APPENDIX 4. ROTTERDAM HANDICAP SCALE (RHS) 
 

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APPENDIX 5. FATIGUE SEVERITY SCALE (FSS) 
 

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APPENDIX 6. PROMIS INSTRUMENTS 
 

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APPENDIX 7. PATIENT-REPORTED OUTCOMES: AVAILABLE 
LANGUAGES 
Rasch-built 
Pompe-specific 
Activity 
(R-PAct) Scale 
Rotterdam 
Handicap 
Scale (RHS) 
Fatigue 
Severity 
Scale 
(FSS) 
PROMIS 
Dyspnea 
PROMIS 
Fatigue 
PROMIS 
Physical 
Functioning 
PROMIS 
Upper 
Extremity 
English 
German 
Dutch 
English 
Dutch 
German 
English 
Dutch 
German 
English 
Dutch 
German 
English 
Dutch 
German 
English 
Dutch 
German 
English 
Dutch 
German 
(pending) 

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APPENDIX 8. PHYSICIAN GLOBAL IMPRESSION OF CHANGE 
(PGIC) AND SUBJECT GLOBAL IMPRESSION OF 
CHANGE (SGIC) 
 

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