A Long-Term Follow-up Study to Evaluate the Safety and Efficacy of Adeno Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase (G6Pase) in Adults With Glycogen Storage Disease Type Ia (GSDIa)
Conditions: Glycogen Storage Disease Type IA, Von Gierke's Disease (GSD Type Ia)
Sponsor: Ultragenyx Pharmaceutical Inc

Amendment 4 
 
401GSDIA02 
 
 
 
 
A Long-Term Follow-up Study to Evaluate the Safety and Efficacy of Adeno-Associated 
Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase 
(G6Pase) in Adults with Glycogen Storage Disease Type Ia (GSDIa) 
 
Protocol Number: 401GSDIA02 
 
Original Protocol: 30 JAN 2019 
Amendment 1: 17 FEB 2020 
Amendment 2: 23 MAR 2021 
Amendment 3: 06 OCT 2021 
Amendment 4: 03 APR 2023 
 
Brief Title: 
Study of Long-Term Safety and Efficacy of Gene 
Therapy in Glycogen Storage Disease Type Ia 
Product number: 
DTX401 
Indication: 
Glycogen storage disease type Ia 
IND Number:  
17965 
EudraCT Number: 
EU CT Number:  
2018-004473-27 
2023-504004-29-00 
Sponsor:  
Ultragenyx Pharmaceutical Inc. 
60 Leveroni Ct  
Novato, CA 94949 
USA 
Medical Monitor: 
 
 
PPD 
Telephone Number:
Fax Number:
 
This study will be performed in compliance with the protocol, Good Clinical Practice 
(GCP), and all applicable regulatory requirements and guidelines. 
 
Confidentiality Statement: This document and the information it contains is confidential and proprietary and is the 
property of Ultragenyx Pharmaceutical Inc. (Ultragenyx). Unauthorized disclosure, reproduction, transmission, or 
use of this document or information is strictly prohibited. By accepting this document, the recipient agrees that the 
information it contains will not be disclosed without prior written authorization from Ultragenyx, except to the 
extent required to satisfy Institutional Review Board/Independent Ethics Committee procedures, to obtain written 
informed consent from potential subjects, or as required by law.  
PPD
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STATEMENT OF COMPLIANCE 
Protocol Title: A Long-Term Follow-up Study to Evaluate the Safety and Efficacy of 
Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of 
Glucose-6-Phosphatase (G6Pase) in Adults with Glycogen Storage Disease Type Ia (GSDIa) 
Protocol Number: 401GSDIA02, Amendment 4 
INVESTIGATOR SIGNATURE: 
I have read Protocol 401GSDIA02, Amendment 4. I agree to conduct the study as detailed in this 
protocol and in compliance with the Declaration of Helsinki, Good Clinical Practice (GCP), and 
all applicable regulatory requirements and guidelines.  
 
 
 
 
 
 
 
Investigator Signature 
Date 
 
Printed Name: 
 
 
 
SPONSOR SIGNATURE: 
As the Sponsor representative, I confirm that Ultragenyx Pharmaceutical Inc. will comply with 
all Sponsor obligations as detailed in this protocol and in compliance with the Declaration of 
Helsinki, Good Clinical Practice (GCP), and all applicable regulation requirements and 
guidelines. I will ensure that the Investigator is informed of all relevant information that becomes 
available during the conduct of this study.  
 
 
 
 
 
 
 
MD 
Global Clinical Development 
Ultragenyx Pharmaceutical Inc. 
Date 
 
PPD
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PROTOCOL AMENDMENT HISTORY AND SUMMARY OF CHANGES 
The following overview summarizes significant changes to the protocol. 
Version 
Date 
Summary of Changes 
Version 1.0 
30 Jan 2019 
Original Protocol 
Version 2.0 
(Amendment 1) 
17 Feb 2020 
An overview of changes includes the following: 
• Assessments for vector shedding was added only for subjects that did not 
demonstrated clearance in Study 401GSDIA01 (Section 11.3.11, Table 1, 
and Table 2) 
• Section 6.2.3 was updated to reflect the number of ongoing studies with 
DTX401 as of December 2019 
• A complete physical examination was added to the Week 260 (or end of 
study) and Early withdrawal visit (Table 1 and Figure 2) 
• The recommended target carbohydrate range of the prefasting challenge 
dinner meal was decreased from 20-30 g to 15-20 g, and the prefasting 
challenge cornstarch dose was decreased from 35 g to 5 g, to minimize a 
potential insulin spike that could result in abrupt hypoglycemia and to 
normalize baseline glucose levels (Section 11.4.1 and Table 1) 
• Blood sample collection for measurement of glucose and lactate levels 
was added at the beginning of the controlled fasting challenge to provide 
baseline levels (Sections 11.3.7.1 and 11.4.1, and Table 1)  
• Instructions for glucose and lactate samples collected during the fasting 
challenge were corrected to state that samples should be prepared and 
transported in accordance with the site’s standard procedures (Sections 
11.3.7.1 and 11.4.1, and Table 1) 
• Continuous glucose monitoring was added to collect supplemental 
information on glucose level trends throughout the study (Sections 11.4.2 
and 13.5.3, and Table 1)  
• The exploratory study objective and endpoint related to morning glucose 
level were modified to glucose level due to the addition of continuous 
glucose monitoring (Sections 7, 13.5.4, and 13.1.3, and Figure 2) 
• Collection of blood for measurement of lipid levels was added on the 
morning of hospital admission for the fasting challenge (Section 11.4.1 
and Table 1) 
• Collection of blood for measurement of cortisol, fatty acid, glucagon, 
insulin, and ketone levels was added at the beginning and end of the 
fasting challenge, or more frequently at the Investigator’s discretion 
(Sections 11.3.7.2 and 11.4.1, and Table 1) 
• Details regarding the collection of morning glucose levels were clarified, 
including instances in which a subject is unable to use the assigned 
continuous glucose monitor (Section 11.4.2 and Table 1) 
• An enzyme-linked immunospot (ELISPOT) assay was added to assess 
any long-term potential cell-mediated immune responses to DTX401 
(Sections 8.1, 11.3, 11.3.9.1, 13.6, Figure 2, and Table 1) 
• Text was added to clarify that the reporting period for hypoglycemic 
events is throughout the study (Sections 11.3.6 and 13.4.2) 
• The table of Clinical Laboratory Parameters was updated for 
completeness (Table 2) 

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Version 
Date 
Summary of Changes 
• New health-related quality of life assessments (Patient Global Impression 
of Severity and Patient Global Impression of Change) were added to 
guide further development of these assessments (Section 11.6.1 and 
Table 1) 
• Language was added to clarify that a clinically significant change or 
abnormal vital sign measurement will be recorded as an AE or SAE if it 
is felt to be clinically significant in the medical and scientific judgment of 
the Investigator (Section 11.3.2) 
• Language was added to clarify that nonemergent hospitalization for 
cornstarch management will not be considered an SAE (Section 12.1.1) 
• Language was added to clarify that Investigators should rate AE intensity 
based on medical judgment and that the current version of the National 
Cancer Institute Common Terminology Criteria for Adverse Events can 
be used to guide the rating of an adverse event (Section 12.1.2) 
• Language was added to indicate that additional interim analyses may be 
conducted at the Sponsor’s discretion (Section 13.7) 
• Language was added to further clarify the minimum report requirements 
for concomitant therapies, including any changes that occur in 
concomitant medication use, and to guidance on recording concomitant 
procedures (Section 10.5)  
• The type of sample (eg, blood) to be collected was specified (Sections 
11.3.9, 11.3.8, and 11.3.10) 
• The frequency of assessing prescribed diet and diet intake was increased 
to monthly for the duration of the study (Section 11.8.2 and Table 1) 
• The frequency of assessing prescribed cornstarch (or equivalent) and 
cornstarch (or equivalent) intake was increased to monthly for the 
duration of the study. It was also noted that follow-up phone calls may 
occur regularly (approximately once a month) to further discuss if 
adjustments are for a subject’s cornstarch use (Section 11.8.3 and 13.1.3, 
and Table 1) 
• Measurement of weight was added to all study visits for the duration of 
the study (Figure 2 and Table 1) 
• Magnetic resonance imaging was moved from safety assessments to 
efficacy assessments (Sections 8.1, 11.3, and 11.4.4) 
• A liver ultrasound assessment was added to visits occurring in between 
visits with magnetic resonance imaging assessments, specifically at 
Weeks 78, 130, 182, and 234 (Section 11.4.5, Figure 2, and Table 1) 
• Measuring the change from baseline in liver ultrasound results over time 
to 260 weeks following IV administration of DTX401, by dose level was 
added as an exploratory objective and endpoint (Sections 7 and 13.1.3)     
• Language regarding management of GSDIa was clarified (Section 6.1) 
• Language was added to further clarify the process of record retention, 
including specifying record retention for 25 years to align with regulatory 
requirements (Section 14.4.3) 
• The sample size was increased from between 6 and 12 subjects to 
approximately up to 18 subjects due to an expansion in the sample size of 
Study 401GSDIA01 (Sections 8.1.2 and 13.1.4) 

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Version 
Date 
Summary of Changes 
• Additional time points were added for the 24-hour urine collection, 
reflecting a collection at all inpatient visits or visits with a controlled 
fasting challenge (Figure 2 and Table 1)  
• The Schedule of Events table was updated to include a row header 
indicating which visits are inpatient and which visits are outpatient 
(Table 1) 
• The protocol was reformatted, and numbering of sections, figures, and 
tables was updated 
Version 3.0 
(Amendment 2) 
23 Mar 2021 
Changes include the following: 
• The Sponsor’s address has been revised (Title Page). 
• The Coordinating Investigator for the study has been removed (Title Page 
and Section 13.2).  
• The Sponsor Contact was changed from
MD to
MD (Sponsor Signature). 
• The sample size was decreased from “approximately up to 18 subjects” to 
“approximately up to 12 subjects” based on current plans to end 
enrollment in Study 401GSDIA01 after Cohort 4 (Sections 2, 7.1.2, 
and 12.1.4). 
• The following changes were made to the controlled fasting challenge 
assessment (Table 1, Table 2, Sections 10.3.7.1, 10.3.7.2, 10.4.1, and 
12.5.1): 
o The definition of euglycemia for the end of the controlled fasting 
challenge changed from ≥ 60 mg/dL (≥ 3.33 mmol/L) to ≥ 54 mg/dL 
(≥ 3.0 mmol/L).  
o The composition of the dinner meal was updated from a prespecified 
carbohydrate range (15–20 g) to a personalized meal for each subject, 
including a target carbohydrate range and overall composition in 
protein, fats and dietary fiber that is as close as possible to the subject’s 
most current dinner prescription but not higher than the carbohydrate 
content of the dinner prescription recorded at their baseline visit in 
Study 401GSDIA01. 
o The prefasting cornstarch dose was updated from 5 g to match the 
respective subject’s most recent cornstarch prescription and timing post 
dinner, but not higher than the prescribed amount recorded at the 
baseline visit in Study 401GSDIA01. 
o Blood samples on the morning of the controlled fasting challenge were 
updated to include clinical chemistry (including lipid levels), 
hematology, coagulation panel, and urinalysis, to be sent to the central 
laboratory, and samples for AST and ALT levels to be sent to the local 
laboratory for STAT analysis.  
o Blood sample assessments at the beginning and end of the controlled 
fasting challenge were updated to include cortisol, ACTH, free fatty 
acids, glucagon, insulin, C-peptide, growth hormone, IGFBP1, alanine 
and ketone levels (3-hydroxy butyrate), and the instructions regarding 
laboratory sample collection before and during the controlled fasting 
challenge have been revised for clarity. 
o A final sample for glucose, lactate, growth hormone, IGFBP1, ACTH, 
and cortisol measurement has been added 30 minutes after the end of 
the controlled fasting challenge. 
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Version 
Date 
Summary of Changes 
o Capillary glucose measurement has been added, to be performed at the 
same time points as blood collection for STAT analysis.  
• Language was added to specify that liver MRI will be conducted after the 
controlled fasting challenge is complete (Table 1; Figure 2; 
Section 10.4.4). 
• Text was added to clarify the duration of MRI image retention and the 
potential for MRI images to be analyzed to better understand the effect of 
DTX401 on GSDIa or other metabolic deficiencies (Section 10.4.4). 
• The contact information for SAE and pregnancy reporting was updated 
(Sections 11.1.4.2 and 11.4). 
• A new section was added to address changes to the study schedule and/or 
study operations due to the COVID-19 pandemic and the availability of 
remote visits to be performed by Firma Clinical Research is described 
(Section 7.3). 
• A telephone interview (Year 2 – Exit Interview)  to better quantify the 
subject experience in the study has been added at Week 104 (or early 
withdrawal if the subject withdraws prior to Week 104), and added to the 
study endpoints (Table 1; Figure 2; Sections 2, 10.6.2, and 12.1.3). 
• Vector shedding sample collection requirements were clarified to include 
blood samples (Table 1; Sections 10.3.7 and 10.3.11)  
• The option for study visits at Weeks 65, 91, 130, 182, and 234 to be 
conducted via home healthcare and/or telemedicine has been added, if 
extenuating circumstances prevent the subject from attending an in-
person clinical site visit. (Table 1; Section 7.1).  
• The option for a subject to ship the CGM receiver to the clinical site has 
been added, if a study visit is conducted remotely or skipped entirely for 
any reason (Table 1; Section 10.4.2). 
• Text referring to regulatory guidance has been revised to accommodate 
current guidance and future revisions (Section 13.1). 
• The Patient Global Impression of Change (PGI-C) has been added to the 
health-related quality of life assessments (Table 1; Sections 4, 10.6.1, and 
Appendix 5).  
• The numbering of sections was updated as necessary, and the in-text 
reference citations and list of references were reformatted to align with 
current Sponsor document styles. 
Version 4.0 
(Amendment 3) 
06 Oct 2021 
Changes include the following: 
• 
Addition of newly identified risk, based on available published 
literature (Sections 5.2.2 and 5.3) 
o 
Dorsal root ganglion and peripheral nerve pathologies have 
been added as a potential risk with DTX401, based on reports 
from nonclinical studies of other rAAV gene therapy products. 
Subjects will be monitored for this potential risk during 
targeted physical examinations and through collection of 
adverse event data. 
• 
Addition of peripheral and central nervous systems examination to the 
targeted examination (Table 1 and Section 10.3.4). 
Version 5.0  
(Amendment 4) 
03 Apr 2023 
Changes include the following: 

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Version 
Date 
Summary of Changes 
• 
The PPD Medical Monitor was changed from 
 MD to
MD (Title Page). 
• 
The Sponsor Contact was changed from
MD 
to
MD (Sponsor Signature). 
• 
Removed unnecessary planned study period detail from synopsis. 
• 
Additional detail around completed Study 401GSDIA01 has been added 
(Synopsis and Section 5.4). 
• 
Renamed ‘exploratory’ endpoints and objectives to be ‘tertiary’ 
endpoints and objectives (Synopsis, Section 6, and Section 12) to align 
with company standards.  
• 
Revised tertiary objectives to be more descriptive rather than repetitions 
of the tertiary endpoints (Synopsis, Section 6, and Section 12). 
• 
Updated primary, secondary, and tertiary endpoints so the assessments 
are analyzed by cohort and overall rather than dose level (Synopsis, 
Section 6, and Section 12). 
• 
Revised tertiary endpoint “urine albumin” to be “24-hour urine protein” 
(Synopsis, Section 6, and Section 12) for scientific accuracy. 
• 
Revised tertiary endpoint “change from baseline in MRI results of the 
liver” to “change from baseline in liver size and fat fraction (by MRI)” 
to specify what is being examined by MRI (Synopsis, Section 6, and 
Section 12). 
• 
Revised tertiary endpoint “average monthly use of cornstarch” to be 
“average daily use of cornstarch” (Synopsis, Section 6, and Section 12) 
to allow for more precise data collection. 
• 
Removed “the change from baseline in liver ultrasound results over 
time to 260 weeks following IV administration of DTX401” from the 
tertiary endpoint list (Synopsis, Section 6, and Section 12). 
• 
Updated the Week 130, 182, and 234 visits to be “OP/HH” instead of 
“InP/HH” (Table 1).  
• 
Added footnote limiting HRQoL assessments to PGI-S and PGI-C at the 
Week 156, 182, 208, 234, 260, 286, and 312 visits to reduce subject 
burden (Table 1).  
• 
Corrected a clerical error in Table 1: moved the Week 130 visit from 
under the “Follow-up: Year 2” column and into the “Follow-up Years 3-
6 column.” 
• 
Added Week 286 and 312 visits and explanation that subjects can roll 
into the DTX401 disease monitoring program (DMP) upon completion 
of Week 208 in Study 401GSDIA02 with Sponsor approval (Synopsis, 
Table 1, Section 6, Section 7.1.3.1, Section 7.1.3.5, Section 7.2, 
Section 10.3.1, Section 11.1.4.1, and Section 11.1.4.2) to ensure subject 
access to safety follow up ahead of the DMP’s availability. 
• 
Added detail around integrating the analysis from Studies 401GSDIA01 
and 401GSDIA02 (Synopsis and Section 12.3.1) for clarity on statistical 
analysis.  
• 
Added brief title and EU CT Number (Title Page) and new sections 
(Section 7.1.3.2, Section 7.1.3.3, Section 7.1.3.6, Section 7.1.4, and 
Section 13.1.4) to address EU CTR requirements. 
• 
Removed the controlled fasting challenge assessment (and associated 
assessments [24-hour urine collection, lipid levels, cortisol, ACTH, free 
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Version 
Date 
Summary of Changes 
fatty acids, glucagon, insulin, C-peptide, growth hormone, IGFBP1, 
alanine and ketone levels (3-hydroxy butyrate), dinner before controlled 
fasting challenge, cornstarch dose after dinner but before starting 
controlled fasting challenge, and glucose and lactate (venous) sample]) 
from Week 130, 182, and 234 visits (Table 1) to reduce subject burden. 
• 
Removed the liver MRI assessment from Weeks 104, 156, and 208 
visits (Table 1 and Figure 2) to reduce subject burden. 
• 
Shifted liver ultrasound collection from Weeks 130, 182, and 234 to 
Weeks 104, 156, 208, 260, and 312 (Table 1 and Figure 2) to reduce 
subject burden. 
• 
Updated tertiary objectives and endpoints to include assessment of 
lactate levels (Synopsis, Section 6, and Section 12). 
• 
Updated Section 5.2.3 to reflect completed and ongoing clinical studies. 
• 
Updated Section 10.4.2 to include additional instruction around the 
pairing of CGM sensors and the study-issued receiver and the uploading 
of data from the receivers. 

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2. 
PROTOCOL SYNOPSIS 
Name of Sponsor: Ultragenyx Pharmaceutical Inc. (Ultragenyx) 
Ultragenyx Product: DTX401 
Title: A Long-Term Follow-up Study to Evaluate the Safety and Efficacy of Adeno-Associated 
Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase (G6Pase) 
in Adults with Glycogen Storage Disease Type Ia (GSDIa) 
Study Phase: Phase 1/2 
Study Rationale: 
The design of this study is consistent with global regulatory guidelines for protocol design. 
Study 401GSDIA02 is a long-term follow-up study to evaluate the safety and efficacy of 
adenoassociated virus (AAV) serotype 8 (AAV8)-mediated gene transfer of glucose-6-
phosphatase (G6Pase) in adults with glycogen storage disease type Ia (GSDIa). Only subjects 
who received DTX401 in Study 401GSDIA01 are eligible to participate in Study 401GSDIA02. 
Study 401GSDIA01 was a Phase 1/2, open-label safety and dose-finding study of AAV8-
mediated gene transfer of G6Pase in adults with GSDIa, during which subjects received a single 
intravenous (IV) dose of DTX401 with steroids (prednisone) to manage alanine aminotransferase 
(ALT) elevation. Overall, 12 patients were enrolled in following cohorts of 3 subjects each: 
• Cohort 1: Dose 1 (2.0 × 1012 genome copies [GC]/kg) with a reactive steroid regimen 
(prednisone starting dose of 40 mg/day) 
• Cohort 2: Dose 2 (6.0 × 1012 GC/kg) with a reactive steroid regimen (prednisone 
starting dose of 40 mg/day) 
• Cohort 3: Dose 2 (6.0 × 1012 GC/kg) with an optimized reactive steroid regimen 
(prednisone starting dose of 60 mg/day) 
• Cohort 4: Dose 2 (6.0 × 1012 GC/kg) with a prophylactic steroid regimen 
No investigational product (IP) will be administered during Study 401GSDIA02. 
Study Design: 
In Study 401GSDIA01, subjects were followed for 1 year after dosing with DTX401. In Study 
401GSDIA02, subjects will be followed for at least 3 additional years (and up to 5 additional 
years) for a total of 4-6 years of follow-up after administration of DTX401. Subjects will visit 
the study site approximately every 13 weeks during the first year of Study 401GSDIA02 and 
then approximately every 26 weeks through the end of the study at Week 312 (Year 6) for safety 
and efficacy evaluations. A long-term disease monitoring program (DMP) DTX401-CL401 is 
planned.  Once the DMP is available to enroll, and after subjects reach the Week 208 visit in 
Study 401GSDIA02, subjects will transition to the DMP with Sponsor approval.  The Schedule 
of Events is presented in Table 1. 
Objectives: 
Primary Objective 
The primary objective of this study is as follows: 

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• To determine the long-term safety of DTX401 following a single IV dose in adults 
with GSDIa 
Secondary Objective 
The secondary objective of this study is as follows: 
• To evaluate the long-term effect of DTX401 on symptom-free euglycemia in a setting 
of a controlled fasting challenge (CFC) 
Tertiary Objectives 
The tertiary objectives for this study are as follows: 
• To evaluate the long-term effect of DTX401 on lipid profiles (total cholesterol, 
low-density lipoprotein, and triglycerides) 
• To evaluate the long-term effect of DTX401 on uric acid 
• To evaluate the long-term effect of DTX401 on proteinuria 
• To evaluate the long-term effect of DTX401 on liver size and fat content 
• To evaluate the long-term effect of DTX401 on hepatic adenoma progression  
• To assess the long-term impact of DTX401 on cornstarch requirements 
• To assess the long-term impact of DTX401 on glucose homeostasis 
• To assess the long-term impact of DTX401 on the subject's health-related quality of 
life (HRQoL) and sleep quality 
• To describe the long-term immune response to AAV8 capsid proteins after IV 
administration of DTX401 
• To describe the long-term immune response to G6Pase after IV administration of 
DTX401 
• To evaluate the long-term effect of DTX401 on lactate levels 
• To evaluate the long-term effects of DTX401 on the endocrine and metabolic 
responses to fasting 
Study Endpoints: 
The primary endpoint is as follows: 
• The incidence of AEs and SAEs for each cohort and overall assessed by severity and 
relationship to IP 
The secondary endpoint is as follows: 
• The change from Day 0 (Study 401GSDIA01) in time to first hypoglycemic event 
during a controlled fasting challenge over time by cohort and overall, following IV 
administration of DTX401 

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The tertiary endpoints are as follows: 
• Total cholesterol, low-density lipoprotein, and triglycerides, by time point, cohort, 
and overall 
• Uric acid, by time point, cohort, and overall 
• 24-hour urine protein, by time point, cohort, and overall 
• The change from baseline in liver size and fat fraction (by MRI) over time following 
IV administration of DTX401, by cohort, and overall 
• The average daily use of cornstarch (or equivalent) over time, by cohort, and overall 
• Assessment of serum glucose levels over time, summarized by cohort 
• Subject responses to HRQoL and sleep quality assessments over time following IV 
administration of DTX401, by cohort and overall 
• Year 2 – Exit Interviews 
• The development of neutralizing antibodies to AAV8 (as determined by a cell-based 
assay) over time, by cohort, and overall 
• The development of anti-AAV8 binding antibodies (as determined by ELISA) over 
time, by cohort, and overall 
• The development of anti-G6Pase antibodies over time, by cohort, and overall 
• Assessment of lactate levels over time, summarized by cohort and overall 
Number of Sites: Up to 12 global study sites  
Number of Subjects: Approximately 12 subjects 
Study Population: 
Individuals eligible to participate in this study must meet all of the following criteria:  
1. Received DTX401 in Study 401GSDIA01  
2. Willing and able to provide written informed consent after the nature of the study has 
been explained, and prior to any research-related procedures being performed 
3. Willing and able to comply with all scheduled study visits, procedures, and requirements 
Individuals who meet any of the following exclusion criteria will not be eligible to participate in 
the study: 
1. Planned or current participation in any other interventional clinical study that may 
confound the safety or efficacy evaluation of DTX401 during this study 
2. Presence or history of any condition that, in the view of the Investigator, poses a risk to 
subject safety or places the subject at high risk of poor compliance or not completing the 
study or that would significantly affect the interpretation of study results 
Investigational Product, Dosage, and Administration: Not applicable. 

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DTX401: 
No IP will be administered during Study 401GSDIA02. All subjects enrolled in Study 
401GSDIA02 will have received a single IV dose of DTX401 during their participation in Study 
401GSDIA01.  
Reference Therapy: Not applicable. 
Duration of Study: 
In Study 401GSDIA01, subjects were followed for 1 year after dosing with DTX401. In Study 
401GSDIA02, subjects will be followed for at least 3 additional years (and up to 5 additional 
years) for a total of 4-6 years of follow-up after administration of DTX401. The duration of 
Study 401GSDIA02 for each subject is defined as the date the subject provides written informed 
consent through the Week 312 (Year 6) visit. Once the DMP is available to enroll, and after 
subjects reach the Week 208 visit in Study 401GSDIA02, subjects will transition to the DMP 
with Sponsor approval. 
Procedures and Assessments: 
Safety will be assessed based on adverse events (AEs), serious adverse events (SAEs), vital sign 
measurements, body weight, physical examination findings, ECG findings, documented 
symptomatic hypoglycemic events, clinical laboratory assessments (clinical chemistry, 
hematology, coagulation panel, and urinalysis), measurement of neutralizing antibody titer to 
AAV8, measurement of AAV8 binding antibody immunoglobulin G, measurement of cell-
mediated immune response to AAV8 and G6Pase, measurement of antiG6Pase antibodies, and 
concomitant medications. 
Efficacy will be assessed for each cohort and overall based on the change from Day 0 (Study 
401GSDIA01) measurements in time to first hypoglycemic event during a controlled fasting 
challenge over time following administration of DTX401. Other efficacy assessments include 
average daily cornstarch use, glucose levels, liver imaging results, and HRQoL and sleep 
assessments. No control group will be enrolled in Study 401GSDIA02. 
Statistical Considerations: 
The study is expected to enroll approximately up to 12 subjects. This is dependent on the number 
of subjects who enrolled in Study 401GSDIA01 and who meet the eligibility criteria for 
Study 401GSDIA02. The sample size is not based on a power calculation. 
No formal hypothesis will be tested. All statistical evaluations will be descriptive. An integrated 
analysis using data from both Study 401GSDIA01 and Study 401GSDIA02 will be performed to 
summarize and assess the long-term safety and efficacy of DTX401; there will not be a 
standalone analysis of data from only Study 401GSDIA02. 
Interim Analysis 
Administrative analyses may be performed during the study to support registrational activities, 
respond to regulatory inquiries, or at the Sponsor’s discretion. 
Safety Analyses 
The incidence of AEs will be summarized for each cohort and overall by system organ class and 
preferred term. Additionally, AEs may be summarized for each cohort and overall by severity 

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and relationship to IP, if applicable. Serious AEs will be presented for each cohort and overall by 
relationship to IP. Summary tables will present the total numbers of AEs as well as the number 
of subjects with AE incidence by system organ class and preferred term. For incidence of 
relationship to IP, subjects will be counted only once, in the category of the strongest 
relationship to IP within each system organ class/preferred term. All other safety analyses will be 
summarized.  
The safety database for Study 401GSDIA02 will include assessment results from Study 
401GSDIA02 only. 
Efficacy Analyses 
Symptom-free euglycemia will be measured using the duration of controlled fasting challenge. 
The duration of the controlled fasting challenge is defined as time to any of the following three 
conditions: 1) glucose <54 mg/dL (<3.0 mmol/L); 2) signs/symptoms of hypoglycemia; 
3) 15 hours fasting without hypoglycemia. The change from Baseline will be calculated using 
Day 0 in Study 401GSDIA01 as Baseline. All other efficacy analyses will be summarized, at 
minimum.

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Table 1: 
Schedule of Events 
Procedure 
Period 
– 
Follow-up: Year 21 
Follow-up: Years 3-62 
Early 
Withdrawal 
Week 
Visit 1  
(Week 
52)3 
Week 
65 
Week 
78 
Week 
91 
Week 
104 
Week 
130 
Week 
156 
Week 
182 
Week 
208 
Week 
234 
Week 
260  
Week 
2864 
Week 
3124 
Visit 
Window 
(Days) 
±7 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
N/A 
Visit Type 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP 
OP 
InP 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications, therapies, and 
procedures 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
Vital sign measurements 
(heart rate, BP, RR) 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
Body weight measurement 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
24-hour urine collection 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Clinical chemistry, 
hematology, coagulation 
panel, urinalysis 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
Lipid levels 
X8 
 
X8 
 
X8 
 
X8 
 
X8 
 
X8 
 
X8 
X8 
Cortisol, ACTH, free fatty 
acids, glucagon, insulin, C-
peptide, growth hormone, 
IGFBP1, alanine and ketone 
levels (3-hydroxy butyrate) 
X9 
 
X9 
 
X9 
 
X9 
 
X9 
 
X9 
 
 
X9 
AAV8 neutralizing antibody 
testing (cell-based assay) 
X7 
 
 
 
X7 
 
X7 
 
X7 
 
X7 
 
 
X7 

Amendment 4 
 
401GSDIA02 
15 
Confidential 
Procedure 
Period 
– 
Follow-up: Year 21 
Follow-up: Years 3-62 
Early 
Withdrawal 
Week 
Visit 1  
(Week 
52)3 
Week 
65 
Week 
78 
Week 
91 
Week 
104 
Week 
130 
Week 
156 
Week 
182 
Week 
208 
Week 
234 
Week 
260  
Week 
2864 
Week 
3124 
Visit 
Window 
(Days) 
±7 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
N/A 
Visit Type 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP 
OP 
InP 
AAV8 binding antibody 
IgG testing (ELISA) 
X7 
 
 
 
X7 
 
X7 
 
X7 
 
X7 
 
 
X7 
Cell-mediated immune 
response to AAV8 and 
G6Pase (ELISPOT) 
X7 
 
 
 
X7 
 
X7 
 
X7 
 
X7 
 
 
X7 
Anti-G6Pase antibody assay 
X7 
 
 
 
X7 
 
X7 
 
X7 
 
X7 
 
 
X7 
Complete physical 
examination 
X7 
 
 
 
 
 
 
 
 
 
X7,10 
X7,10 
X7 
X7 
Targeted physical 
examination11 
 
X 
X7 
X 
X7 
(X) 
X7 
(X) 
X7 
(X) 
X7,10 
X7,10 
 
 
12-Lead ECG 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
Liver MRI12 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Liver ultrasound 
 
 
X7 
 
X7 
 
X7 
 
X7 
 
X7 
 
X7 
 
AE/SAE monitoring 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X 
X7 
Assessment of symptomatic 
hypoglycemic events 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
Assessment of prescribed 
diet and dietary intake13 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
Assessment of cornstarch 
(or equivalent) use13 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X 
X7 
X7 
CGM14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Amendment 4 
 
401GSDIA02 
16 
Confidential 
Procedure 
Period 
– 
Follow-up: Year 21 
Follow-up: Years 3-62 
Early 
Withdrawal 
Week 
Visit 1  
(Week 
52)3 
Week 
65 
Week 
78 
Week 
91 
Week 
104 
Week 
130 
Week 
156 
Week 
182 
Week 
208 
Week 
234 
Week 
260  
Week 
2864 
Week 
3124 
Visit 
Window 
(Days) 
±7 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
N/A 
Visit Type 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP 
OP 
InP 
Collect and re-issue 
Morning Glucose Level 
monitoring worksheet15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of morning 
glucose levels16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dinner before controlled 
fasting challenge17 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Cornstarch dose after dinner 
but before starting 
controlled fasting 
challenge18 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Controlled fasting 
challenge19 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Glucose and lactate 
(venous) sample (local 
laboratory [STAT 
sample])20 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Blood, saliva, urine, and 
stool for vector shedding 
(qPCR)21 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 

Amendment 4 
 
401GSDIA02 
17 
Confidential 
Procedure 
Period 
– 
Follow-up: Year 21 
Follow-up: Years 3-62 
Early 
Withdrawal 
Week 
Visit 1  
(Week 
52)3 
Week 
65 
Week 
78 
Week 
91 
Week 
104 
Week 
130 
Week 
156 
Week 
182 
Week 
208 
Week 
234 
Week 
260  
Week 
2864 
Week 
3124 
Visit 
Window 
(Days) 
±7 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
±14 
N/A 
Visit Type 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP/ 
HH5 
InP 
OP 
OP 
InP 
HRQoL (PROMIS-29, 
PROMIS Social Isolation, 
PGI-S, PGI-C), and sleep 
quality (Pittsburgh Sleep 
Quality Index) assessments 
X 
X 
X 
X 
X 
X 
X22 
X22 
X22 
X22 
X22 
X22 
X22 
X 
Endpoint Outcomes 
Interview (Year 2 - Exit 
Interview)23 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Abbreviations: AAV8 = adeno-associated virus serotype 8; ACTH = adrenocorticotropic hormone ; AE = adverse event; BP = blood pressure; CGM = 
continuous glucose monitoring; ECG = electrocardiogram; ELISA = enzyme-linked immunosorbent assay; ELISPOT = enzyme-linked immunospot assay; 
EOS = end of study; EW = early withdrawal; G6Pase = glucose-6-phosphatase; HH = home healthcare visit; HRQoL = health-related quality of life; IGFBP1 
= insulin-like growth factor-binding protein 1; IgG = immunoglobulin G; InP = inpatient; MRI = magnetic resonance imaging; N/A = not applicable; OP = 
outpatient; PGI-C = Patient Global Impression of Change; PGI-S = Patient Global Impression of Severity; RR = respiratory rate; SAE = serious adverse 
event. 
Note: The periods and weeks in Study 401GSDIA02 begin at Year 2 and Week 52, respectively, and are relative to a time zero from the administration of 
DTX401 in Study 401GSDIA01. The study duration for Study 401GSDIA02 is up to 5 years. The end of study visit occurs at Week 208 or any visit thereafter 
upon availability of the DMP to enroll.  
1  During the first year of Study 401GSDIA02, visits will occur approximately every 13 weeks. 
2  After the first year of Study 401GSDIA02, visits will occur approximately every 26 weeks.   
3  The first visit for Study 401GSDIA02 may coincide with the Week 52/EOS/EW visit for Study 401GSDIA01. Assessments required for Study 401GSDIA02 
that are the same as those performed during the Week 52/EOS/EW visit for Study 401GSDIA01 do not need to be repeated if written informed consent for 
Study 401GSDIA02 is obtained before the Week 52/EOS/EW assessments are performed for Study 401GSDIA01. Assessments may be performed on more 
than 1 day provided that all assessments are completed, and results are available within the 7-day window. 
4  Visit will only be conducted if a subject has not yet entered the DTX401 DMP.  Visit can be outpatient but should be in-clinic. 
5 At Weeks 65, 91, 130, 182, and 234, every effort will be made to conduct an on-site assessment. However, under extenuating subject circumstances that, in 
the Investigator’s opinion, make an on-site visit not feasible, and after all reasonable measures to enable the subject's onsite visit have been exhausted, a home 
healthcare visit and/or telemedicine assessment may be conducted.  At these time points, the assessments in parentheses “(X)” will not be performed if the 
visit is changed to a home healthcare visit.  

Amendment 4 
 
401GSDIA02 
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Confidential 
6 
 Any AEs that are ongoing at the completion of Study 401GSDIA01 will be considered medical history in Study 401GSDIA02. 
7 Assessments to be performed prior to the controlled fasting challenge.  
8 A blood sample for measurement of lipid levels will be collected on the morning of hospital admission for each controlled fasting challenge at approximately 
the same time starting at Day 0 (Study 401GSDIA01). The sample should be collected at least 2 to 4 hours after the subject’s last meal. 
9 If possible, a blood sample for measurement of cortisol, ACTH, free fatty acids, glucagon, insulin, C-peptide, growth hormone, IGFBP1, alanine and ketone 
levels (3-hydroxy butyrate) will be collected at the beginning and end of the controlled fasting challenge, or more frequently at the investigator’s discretion. 
10 A targeted physical examination will occur if a subject is not completing an end of study visit and a complete physical examination will occur if a subject is 
having an end of study visit. 
11  A targeted physical examination will include assessment of the skin, the abdomen with documentation of liver and spleen size, and the respiratory, 
cardiovascular, gastrointestinal, and peripheral and central nervous systems. 
12 An MRI of the liver will be performed to quantify glycogen and fatty liver content. The MRI will be performed after the controlled fasting challenge is 
complete for the Week 52 (Visit 1) only to avoid having to replace the CGM sensor prior to the fasting challenge. 
13 Assessment of daily prescribed diet and dietary intake as well as assessment of cornstarch (or equivalent) use will be reviewed at each study visit, and if 
possible, on a monthly basis through the final study visit. Follow-up phone calls may occur regularly (approximately once a month) to further discuss if 
adjustments are needed for a subject’s cornstarch use. 
14 Supplemental information on glucose level trends will be collected using a CGM device. If subjects do not already have a study-issued CGM device (as these 
are provided in Study 401GSDIA01), a study-issued CGM will be provided. Subjects should bring their CGM device to each visit, containing CGM data 
from the 28 days prior to visit). If a study visit is conducted remotely (home healthcare visit or telemedicine), or if a study visit is skipped entirely for any 
reason, arrangements will be made for the subject to ship the CGM receiver (ideally, containing CGM data from the 28 days prior to the remote/missed visit) 
to the clinical site. Data from the subject’s CGM device will be transferred to the Sponsor throughout the study, including a final data transfer at the end of 
the Week 312 visit or early withdrawal. 
15 If a subject is unable to use the assigned CGM, the subject should collect morning glucose levels at least 2 mornings per week throughout the study and 
record the values on the Morning Glucose Level monitoring worksheet provided at Visit 1. Subjects should measure their morning glucose level using their 
own glucose monitoring device before taking their morning dose of cornstarch. Subjects will be instructed to bring the completed worksheet to each study 
visit. 
16 If the subject was unable to use the assigned CGM but was able to complete the Morning Glucose Level monitoring worksheet, the subject’s worksheet will 
be collected and reviewed at the time points specified in Table 1, and a new worksheet will be provided to the subject.  
17 Before the controlled fasting challenge begins, the study site will provide dinner for the subject. The dinner meal will be personalized for each subject, and 
will include a target carbohydrate range and overall composition in protein, fats and dietary fibers that is as close as possible to the subject’s most current 
dinner prescription, but not higher in carbohydrate content than their dinner prescription recorded at their baseline visit in Study 401GSDIA01.  
18 After dinner, subjects will be given an oral dose of cornstarch equivalent per their most recent cornstarch prescription, at approximately the same time that 
they typically take it, but no later than 3 hours post dinner. The amount of cornstarch administered should not be higher than the prescribed amount recorded 
at their baseline visit in Study 401GSDIA01.  
19 In addition to the specified time points, if clinically indicated, the controlled fasting challenge can be performed at an unscheduled visit.   
20 During the controlled fasting challenge, blood samples for glucose and lactate (venous) will be collected at the beginning of the controlled fasting challenge 
and approximately every 60 minutes (±5 minutes) until glucose levels are at or below 70 mg/dL (≤3.9 mmol/L). Once glucose levels are at or below 
70 mg/dL (≤3.9 mmol/L), blood samples for glucose and lactate (venous) will be collected approximately every 30 minutes (±5 minutes) until the subject’s 
glucose level drops below 54 mg/dL (<3.0 mmol/L), the subject experiences symptoms of hypoglycemia per the Investigator’s discretion, or the fast reaches 
15 hours without hypoglycemia, whichever occurs first. Samples should be sent to the local laboratory (STAT sample) and results should be available within 
30 minutes or less of the blood sample collection for subject safety. Samples should be prepared and transported to the local laboratory in accordance with the 

Amendment 4 
 
401GSDIA02 
19 
Confidential 
site’s standard procedures. Capillary glucose will be performed at the same time points as blood samples for STAT analysis of glucose and lactate. Results of 
the capillary glucose and readings from CGM at corresponding time points will be noted on a controlled fasting challenge results sheet. At Week 312 visit a 
STAT lactate will be collected. A STAT glucose will not be collected at the Week 312 visit. 
21 Blood, saliva, urine, and stool for vector shedding will only be collected for subjects who did not demonstrate clearance in Study 401GSDIA01. Samples for 
vector shedding analysis will be collected until at least 3 consecutive negative results are obtained for each sample matrix. ‘ 
22 Only PGI-S and PGI-C will be collected at the visit. 
23 A 30-minute scripted telephone interview will be conducted by a third-party vendor, Endpoint Outcomes, to better quantify the subject experience in the 
study. The interview will be conducted at Week 104, or at the Early Withdrawal visit if the subject withdraws prior to Week 104. 

Amendment 4 
 
401GSDIA02 
20 
Confidential 
3. 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
STATEMENT OF COMPLIANCE .................................................................................................2 
PROTOCOL AMENDMENT HISTORY AND SUMMARY OF CHANGES ..............................3 
2. 
PROTOCOL SYNOPSIS .............................................................................................9 
3. 
TABLE OF CONTENTS ...........................................................................................20 
4. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...............................25 
5. 
BACKGROUND ........................................................................................................27 
5.1. 
Overview of GSDIa ....................................................................................................27 
5.2. 
Overview of DTX401 Development ..........................................................................28 
5.2.1. 
Brief Description of DTX401 .....................................................................................28 
5.2.2. 
Nonclinical Studies .....................................................................................................29 
5.2.3. 
Previous and Ongoing Clinical Studies ......................................................................29 
5.3. 
Summary of Overall Risks and Potential Benefits .....................................................29 
5.4. 
Study Rationale ...........................................................................................................30 
6. 
STUDY OBJECTIVES ..............................................................................................31 
7. 
INVESTIGATIONAL PLAN .....................................................................................32 
7.1. 
Overall Study Design and Plan ...................................................................................32 
7.1.1. 
Number of Study Sites ................................................................................................34 
7.1.2. 
Number of Subjects ....................................................................................................34 
7.1.3. 
Estimated Study Duration ...........................................................................................34 
7.1.3.1. 
Study Duration for Subjects ........................................................................................34 
7.1.3.2. 
Selection of Study Population ....................................................................................34 
7.1.3.3. 
Start of Study Definition .............................................................................................34 
7.1.3.4. 
Eligibility Determination Period (Visit 1 [Week 52]) ................................................34 
7.1.3.5. 
Study Completion .......................................................................................................35 
7.1.3.6. 
Continued Access to Study Intervention after the End of Study ................................35 
7.1.4. 
Subject Input into Design ...........................................................................................35 
7.2. 
Discussion of Study Design, Including Choice of Control Group .............................35 
7.3. 
Changes to the Protocol due to COVID-19 ................................................................35 
8. 
STUDY POPULATION .............................................................................................37 

Amendment 4 
 
401GSDIA02 
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Confidential 
8.1. 
Inclusion Criteria ........................................................................................................37 
8.2. 
Exclusion Criteria .......................................................................................................37 
8.3. 
Removal of Subjects from Therapy or Assessment ....................................................37 
9. 
TREATMENTS ..........................................................................................................39 
9.1. 
Investigational Product ...............................................................................................39 
9.2. 
Reference Therapy ......................................................................................................39 
9.3. 
Dosage Administration ...............................................................................................39 
9.4. 
Dosage Rationale ........................................................................................................39 
9.5. 
Concomitant Medications, Therapies, and Procedures ...............................................39 
9.6. 
Restricted or Prohibited Medications, Devices, and Procedures ................................39 
9.7. 
Treatment Compliance ................................................................................................39 
9.8. 
Treatment Group Allocation .......................................................................................39 
9.8.1. 
Method of Assigning Subjects to Treatment Groups .................................................39 
9.8.2. 
Blinding ......................................................................................................................40 
10. 
STUDY PROCEDURES ............................................................................................41 
10.1. 
Study Schedule ...........................................................................................................41 
10.2. 
Informed Consent and Eligibility Requirements ........................................................41 
10.3. 
Safety Assessments .....................................................................................................41 
10.3.1. 
Adverse Events ...........................................................................................................41 
10.3.2. 
Vital Sign Measurements ............................................................................................41 
10.3.3. 
Body Weight ...............................................................................................................42 
10.3.4. 
Physical Examinations ................................................................................................42 
10.3.5. 
Electrocardiograms .....................................................................................................42 
10.3.6. 
Hypoglycemic Events .................................................................................................42 
10.3.7. 
Clinical Laboratory Tests ...........................................................................................42 
10.3.7.1. 
Lactate .........................................................................................................................43 
10.3.7.2. 
Other Controlled Fasting Challenge Laboratory Assessments ...................................44 
10.3.7.3. 
24-Hour Urine Collection ...........................................................................................44 
10.3.8. 
Adeno-Associated Virus Serotype 8 Binding Antibody Immunoglobulin G 
Assay ...........................................................................................................................44 
10.3.9. 
Neutralizing Antibodies to AAV8 ..............................................................................44 
10.3.9.1. 
Cell-Mediated Immune Response ...............................................................................44 
10.3.10. 
Anti-Glucose-6-Phosphatase Antibody Assay ...........................................................44 

Amendment 4 
 
401GSDIA02 
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10.3.11. 
Vector Shedding .........................................................................................................45 
10.3.12. 
Pregnancy Testing and Contraception Requirements .................................................45 
10.4. 
Disease-Specific Clinical Assessments ......................................................................45 
10.4.1. 
Symptom-Free Euglycemia (Controlled Fasting Challenge) .....................................45 
10.4.2. 
Continuous Glucose Monitoring.................................................................................47 
10.4.3. 
Morning Glucose Assessments ...................................................................................47 
10.4.4. 
Magnetic Resonance Imaging .....................................................................................47 
10.4.5. 
Liver Ultrasound .........................................................................................................48 
10.5. 
Biomarker Assessments ..............................................................................................48 
10.6. 
Patient-Reported and Clinician-Reported Outcomes ..................................................48 
10.6.1. 
Health-Related Quality of Life and Sleep Quality Assessments ................................48 
10.6.2. 
Endpoint Outcomes Interview (Year 2 – Exit Interview) ...........................................48 
10.7. 
Pharmacokinetic Assessments ....................................................................................49 
10.8. 
Other Assessments ......................................................................................................49 
10.8.1. 
Demographic and Medical History Assessments .......................................................49 
10.8.2. 
Assessment of Prescribed Diet and Dietary Intake .....................................................49 
10.8.3. 
Assessment of Cornstarch (or Equivalent) Use ..........................................................49 
10.9. 
Appropriateness of Measurements .............................................................................49 
11. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING....................50 
11.1. 
Reporting and Follow-up of Adverse Events .............................................................50 
11.1.1. 
Adverse Event Terminology .......................................................................................50 
11.1.2. 
Severity of Adverse Events ........................................................................................51 
11.1.3. 
Relationship of Adverse Events to Investigational Product .......................................52 
11.1.4. 
Adverse Event Reporting ............................................................................................52 
11.1.4.1. 
General ........................................................................................................................52 
11.1.4.2. 
Requirements for Immediate Reporting of Serious Adverse Events and 
Serious Adverse Drug Reactions ................................................................................52 
11.1.4.3. 
Requirements for Reporting of Pregnancy in Subject or Partner ...............................53 
11.1.5. 
Safety Communication Plan .......................................................................................53 
11.1.5.1. 
Serious Adverse Drug Reaction Reporting .................................................................53 
11.1.5.2. 
Urgent Safety Matters and Non-SUSAR Reporting ...................................................54 
11.2. 
Safety Data Monitoring ..............................................................................................54 
11.3. 
Study Termination or Suspension Due to Safety Events ............................................54 

Amendment 4 
 
401GSDIA02 
23 
Confidential 
11.4. 
Safety Contact Information .........................................................................................54 
12. 
STATISTICAL METHODS .......................................................................................55 
12.1. 
Endpoints and Determination of Sample Size ............................................................55 
12.1.1. 
Primary Endpoint ........................................................................................................55 
12.1.2. 
Secondary Endpoint ....................................................................................................55 
12.1.3. 
Tertiary Endpoints ......................................................................................................55 
12.1.4. 
Sample Size Considerations .......................................................................................56 
12.2. 
Analysis Population ....................................................................................................56 
12.2.1. 
Full Analysis Set .........................................................................................................56 
12.3. 
Planned Methods of Analysis .....................................................................................56 
12.3.1. 
General Principles .......................................................................................................56 
12.4. 
Safety Analyses ..........................................................................................................56 
12.4.1. 
Adverse Events ...........................................................................................................56 
12.4.2. 
Hypoglycemic Events .................................................................................................56 
12.4.3. 
MRI Results of the Liver ............................................................................................57 
12.4.4. 
Clinical Laboratory Assessments ...............................................................................57 
12.5. 
Efficacy Analyses .......................................................................................................57 
12.5.1. 
Symptom-Free Euglycemia ........................................................................................57 
12.5.2. 
Use of Cornstarch (or Equivalent) ..............................................................................57 
12.5.3. 
Continuous Glucose Monitoring.................................................................................57 
12.5.4. 
Morning Glucose Levels .............................................................................................57 
12.5.5. 
Health-Related Quality of Life and Sleep Quality .....................................................57 
12.6. 
Immunogenicity Analysis ...........................................................................................57 
12.7. 
Interim Analyses .........................................................................................................57 
12.8. 
Data Monitoring Committee .......................................................................................58 
13. 
STUDY ETHICS AND CONDUCT ..........................................................................59 
13.1. 
Ethics ..........................................................................................................................59 
13.1.1. 
Institutional Review Board or Independent Ethics Committee and Competent 
Health Authority .........................................................................................................59 
13.1.2. 
Ethical Conduct of Study ............................................................................................59 
13.1.3. 
Subject Information and Consent ...............................................................................59 
13.1.4. 
Data Protection, Anonymization and Security ...........................................................60 
13.1.5. 
Future Use of Stored Study Samples ..........................................................................61 

Amendment 4 
 
401GSDIA02 
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Confidential 
13.2. 
Investigators and Study Administrative Structure ......................................................61 
13.2.1. 
Investigator Documentation ........................................................................................61 
13.3. 
Investigational Product Accountability ......................................................................61 
13.4. 
Data Handling and Record Keeping ...........................................................................62 
13.4.1. 
Case Report Forms and Source Documents ...............................................................62 
13.4.2. 
Data Quality Assurance ..............................................................................................62 
13.4.3. 
Record Retention ........................................................................................................62 
13.5. 
Financing and Insurance .............................................................................................63 
13.6. 
Publication Policy .......................................................................................................63 
14. 
REFERENCES ...........................................................................................................64 
15. 
APPENDICES ............................................................................................................67 
APPENDIX 1. PROMIS-29 ........................................................................................................68 
APPENDIX 2. PROMIS SOCIAL ISOLATION – SHORT FORM 4A ....................................63 
APPENDIX 3. PITTSBURGH SLEEP QUALITY INDEX (PSQI) ..........................................65 
APPENDIX 4. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) .........................70 
APPENDIX 5. PATIENT GLOBAL IMPRESSION OF CHANGE (PGI-C)............................72 
 
List of Tables 
Table 1: 
Schedule of Events .....................................................................................................14 
Table 2: 
Clinical Laboratory Parameters ..................................................................................43 
Table 3: 
General Guidelines for Grading Events Not Captured by the CTCAE ......................51 
Table 4: 
Ultragenyx Contact Information for SAE Reporting ..................................................54 
 
List of Figures 
Figure 1: 
Overview of Glycogenesis and Glycogenolysis .........................................................27 
Figure 2: 
Study Design ...............................................................................................................33 
 

Amendment 4 
 
401GSDIA02 
25 
Confidential 
4. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition or Explanation 
AAV 
adeno-associated virus 
AAV8 
adeno-associated virus serotype 8 
ACTH  
adrenocorticotropic hormone 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
CFR 
Code of Federal Regulations 
CGM 
continuous glucose monitoring  
DMP 
disease monitoring program 
DRG 
dorsal root ganglion 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
ELISPOT 
enzyme-linked immunospot assay 
EOS 
end of study 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
EW 
early withdrawal 
FDA 
Food and Drug Administration 
G6P 
glucose-6-phosphate 
G6Pase 
glucose-6-phosphatase (protein) 
G6PC 
glucose-6-phosphatase (gene) 
G6pc-/- 
glucose-6-phosphatase knockout 
GC 
genome copies 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GSDIa 
glycogen storage disease type Ia  
HCA 
hepatocellular adenoma 
HCC 
hepatocellular carcinoma 
HRQoL 
health-related quality of life 
ICF 
informed consent form 
ICH 
International Council for Harmonisation  

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Abbreviation 
Definition or Explanation 
IEC 
Independent Ethics Committee 
IGFBP1 
insulin-like growth factor-binding protein 1 
IgG 
immunoglobulin G 
IND 
Investigational New Drug (application) 
InP 
inpatient 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
LFT 
liver function test 
MRI 
magnetic resonance imaging 
OP 
outpatient 
PGI-S 
Patient Global Impression of Severity 
PGI-C 
Patient Global Impression of Change 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SUSAR 
suspected unexpected serious adverse reaction 
 

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5. 
BACKGROUND 
5.1. 
Overview of GSDIa 
Glucose-6-phosphatase is a glucose-6-phosphate (G6P) hydrolase located in the endoplasmic 
reticulum that is primarily expressed in the liver, kidneys, and intestine. It is a highly 
hydrophobic protein with 9 transmembrane domains (Pan et al., 1998). The amino and carboxyl 
termini of the glucose-6-phosphatase (G6Pase) protein are located on opposite sides of the 
endoplasmic reticulum membrane, with the active site of the enzyme facing the endoplasmic 
reticulum lumen (Lei et al., 1993; Lei et al., 1995b; Lei et al., 1995c). Glucose-6-phosphatase is 
responsible for catalyzing the terminal step in hepatic and renal glycogenolysis and 
gluconeogenesis (Figure 1): the hydrolysis of G6P to glucose and inorganic phosphate provides a 
significant amount of circulating glucose (Foster and Nordlie, 2002). In patients with glycogen 
storage disease type Ia (GSDIa), free glucose molecules are not generated for export into the 
body’s circulation, and as a result, glucose from glycogen stores is unavailable during periods of 
fasting, resulting in severe hypoglycemia. The excess G6P molecules are shunted toward the 
production of triglycerides (eventually stored as fat) and the pentose-phosphate pathway (leading 
to increased uric acid production). Additionally, during periods of prolonged hypoglycemia, an 
increased rate of glycolysis and catabolism of muscle and fats results in a build-up of lactate 
(Chou and Mansfield, 1999; Chou, 2001; van Schaftingen and Gerin, 2002). 
Figure 1: 
Overview of Glycogenesis and Glycogenolysis 
 
Glycogen storage disease type Ia, also known as von Gierke disease, is a severe autosomal 
recessive inborn error of metabolism that is caused by mutations of the glucose-6-phosphatase 
(G6PC) gene located on chromosome 17q21 (Lei et al., 1993; Chou, 2001). Patients affected by 
GSDIa present with severe hypoglycemia and seizures at a few months of age. Like many other 
inherited disorders, GSDIa can be readily detected by screening a bloodspot sample for one of 
several common mutations (Lei et al., 1995a). The importance of diagnosing and treating GSDIa 
early is emphasized by the severe complications that arise when the disease is left untreated, 

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including life-threatening hypoglycemia, severe lactic acidosis, growth failure, renal Fanconi 
syndrome, and pancreatitis. Acute complications of GSDIa, such as hypoglycemia, severe 
metabolic acidosis, and renal tubular dysfunction, respond favorably to and can be prevented 
with strict dietary restrictions and frequent consumption of uncooked cornstarch. However, these 
restrictions have significant limitations and require constant vigilance to avoid acute metabolic 
decompensation that is accompanied by life-threatening hypoglycemia and lactic acidosis. In 
addition, dietary restrictions are often not an effective means of preventing the long-term clinical 
complications associated with GSDIa, including proteinuria (that may progress to renal failure), 
growth retardation, osteopenia, and the formation of hepatocellular adenomas (HCAs) and 
hepatocellular carcinomas (HCCs) (Chen et al., 1988; Wolfsdorf and Crigler, 1997; Wolfsdorf et 
al., 1997; Wolfsdorf et al., 1999). 
Complications, such as hepatomegaly (resulting from the pathological accumulation of glycogen 
in the liver), an increase in the number and size of HCAs, and the development of HCCs become 
more common as individuals with GSDIa age (Franco et al., 2005). For example, HCAs are 
present in 70% to 80% of GSDIa patients over the age of 25 years, with up to 10% of HCAs 
developing into life-threatening HCCs (Franco et al., 2005; Reddy et al., 2007; Lee et al., 2012). 
Orthotopic liver transplantation has become a treatment option for patients and has been shown 
to correct hypoglycemia and other biochemical abnormalities associated with GSDIa, as well as 
result in an increase in body height (Matern et al., 1999; Boers et al., 2014). These results 
provide evidence for the efficacy and benefit of restoring G6PC expression in the liver of 
patients with GSDIa. However, given that liver transplantation is limited by donor availability 
and is associated with significant risk of morbidity and mortality including a very high rate of 
renal failure (Davis and Weinstein, 2008; Boers et al., 2014), there is a significant unmet medical 
need for a treatment that allows for sustained euglycemia and prevention of the long-term 
complications and life-threatening hypoglycemia that are associated with GSDIa. In nonclinical 
studies, adeno-associated virus (AAV) serotype 8 (AAV8)-mediated delivery of G6PC in mice 
and dogs with GSDIa has restored G6Pase activity and ameliorated disease sequelae (Koeberl et 
al., 2009; Koeberl et al., 2008; Weinstein et al., 2010; Chou and Mansfield, 2011), providing 
evidence that gene transfer could have significant benefit in patients with GSDIa. 
5.2. 
Overview of DTX401 Development 
A brief overview of existing information on DTX401 is provided below; a comprehensive 
review of available data is contained in the Investigator’s Brochure (IB) provided by Ultragenyx, 
which should be reviewed prior to initiating the study. 
5.2.1. 
Brief Description of DTX401 
DTX401 is a nonreplicating, recombinant AAV8 vector that contains a codon-optimized, wild-
type human G6PC coding sequence. DTX401 demonstrates thermal stability, which is a general 
property of AAV and parvoviruses. DTX401 is supplied as a slightly hyperosmotic buffered 
formulation solution of approximately 400 milliosmole at pH 8.0. DTX401 is a homogeneous, 
monodisperse solution that is clear and colorless without visible particulates. 

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5.2.2. 
Nonclinical Studies 
Ultragenyx has conducted a comprehensive nonclinical program to support the single 
intravenous (IV) administration of DTX401. Studies of potential clinical significance and 
relevance to this protocol are summarized below. 
The safety and tolerability of DTX401 were evaluated in a non-Good Laboratory Practice (GLP) 
nonclinical study. Doses up to 1.0×1013 genome copies (GC)/kg were evaluated in the neonatal 
glucose-6-phosphatase knockout (G6pc-/-) mouse model. Results demonstrated the ability of the 
candidate transgene constructs to prolong survival, improve biochemical markers of GSDIa 
disease, and drive persistent expression of G6Pase in the liver. The potential toxicity and 
biodistribution of DTX401 were evaluated in a GLP nonclinical study. Doses up to 6.5×1013 
GC/kg were evaluated in C57BL/6 mice. In this study, adverse histopathological findings were 
observed in the spleen and mandibular and mesenteric lymph nodes (lymphoid hyperplasia) and 
liver (single cell necrosis/apoptosis, Kupffer cell hypertrophy/hyperplasia), at Day 29 at the 
highest dose (6.5×1013 GC/kg); accompanied by increases in clinical chemistry (including 
alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and hematology 
parameters. These findings are potentially due to an immune response to the administration of a 
high dose of a foreign protein, as a persistent interferon-γ T-cell response was observed to the 
AAV8 capsid. The adverse findings were at the high dose only, and completely resolved by Day 
92 with no additional intervention. Based on these findings, the no observed adverse effect level 
of DTX401 in this study was determined to be 1×1013 GC/kg. 
Dorsal root ganglion (DRG) and peripheral nerve pathologies have been reported in nonhuman 
primates, piglets, and mice administered rAAV gene therapy products (Bolt et al., 2021; Van 
Alstyne et al., 2021; Hordeaux et al., 2020a; Hordeaux et al., 2020b; Hinderer et al., 2018; 
Schuster et al., 2014). The clinical relevance and translation of these nonclinical DRG and nerve 
pathologies is not known. The main parameters demonstrated to affect severity of the DRG 
findings was route of administration, where IV dosing was shown to be more resistant to DRG 
lesions compared to CNS routes of delivery, and vector dose (> 1 × 1013 GC/kg). DTX401 is 
designed to be hepatotropic and show little transgene expression in tissues outside the liver. 
The totality of the available literature information and DTX401 nonclinical data, combined with 
the used clinical dose (6.0 × 1012 GC/kg), use of a liver-specific promoter, and IV route of 
administration, suggests that the risk of DRG and peripheral nerve-related toxicities occurring 
with DTX401 treatment is low. Despite the low risk with DTX401, DRG pathology is currently 
being assessed as part of the 92-day GLP toxicology study in mice as a follow up to these recent 
publications. 
5.2.3. 
Previous and Ongoing Clinical Studies 
Study 401GSDIA01 was completed in November 2022 and two clinical studies with DTX401 
(Studies 401GSDIA02 and DTX401-CL301) are ongoing. 
5.3. 
Summary of Overall Risks and Potential Benefits 
Adeno-associated virus vectors represent a class of viral vectors that are nonreplicating, 
nonintegrating, and present a low risk for gene therapy-related delayed adverse reactions. 

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Recommended long term safety monitoring for subjects enrolled in AAV gene therapy clinical 
trials is a minimum of 5 years (CBER, 2006; CHMP, 2009).  
Subjects enrolled into Study 401GSDIA02 will be followed for long-term safety and efficacy of 
the single IV infusion of DTX401 administered in Study 401GSDIA01. Subjects will not receive 
any additional doses of DTX401. Despite the low risk of DRG and peripheral nerve-related 
toxicities as mentioned in Section 5.2.2, subjects will be regularly assessed for clinically 
meaningful signs of sensory neuropathy throughout the 401GSDIA02 study, and if this event 
occurs, they will be further evaluated and closely monitored. The overall risk and potential 
benefits for subjects enrolled into Study 401GSDIA02 are considered acceptable for a follow-up 
study. 
5.4. 
Study Rationale 
Study 401GSDIA02 is a long-term follow-up study to evaluate the safety and efficacy of AAV8-
mediated gene transfer of G6Pase in adults with GSDIa. Only subjects who received DTX401 in 
Study 401GSDIA01 are eligible to participate in Study 401GSDIA02. Study 401GSDIA01 was a 
Phase 1/2, open-label safety and dose-finding study of AAV8-mediated gene transfer of G6Pase 
in adults with GSDIa, during which subjects received a single IV dose of DTX401 with steroids 
(prednisone) to manage alanine aminotransferase (ALT) elevation. Overall, 12 patients were 
enrolled in following cohorts of 3 subjects each: 
• Cohort 1: Dose 1 (2.0 × 1012 genome copies [GC]/kg) with a reactive steroid regimen 
(prednisone starting dose of 40 mg/day) 
• Cohort 2: Dose 2 (6.0 × 1012 GC/kg) with a reactive steroid regimen (prednisone 
starting dose of 40 mg/day) 
• Cohort 3: Dose 2 (6.0 × 1012 GC/kg) with an optimized reactive steroid regimen 
(prednisone starting dose of 60 mg/day) 
• Cohort 4: Dose 2 (6.0 × 1012 GC/kg) with a prophylactic steroid regimen 
No investigational product (IP) will be administered during Study 401GSDIA02. 

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6. 
STUDY OBJECTIVES  
Primary Objective 
The primary objective of this study is as follows: 
• To determine the long-term safety of DTX401 following a single IV dose in adults 
with GSDIa 
Secondary Objective 
The secondary objective of this study is as follows: 
• To evaluate the long-term effect of DTX401 on symptom-free euglycemia in a setting 
of a controlled fasting challenge 
Tertiary Objectives  
The tertiary objectives of this study are as follows: 
• To evaluate the long-term effect of DTX401 on lipid profiles (total cholesterol, 
low-density lipoprotein, and triglycerides) 
• To evaluate the long-term effect of DTX401 on uric acid 
• To evaluate the long-term effect of DTX401 on proteinuria 
• To evaluate the long-term effect of DTX401 on liver size and fat content 
• To evaluate the long-term effect of DTX401 on hepatic adenoma progression  
• To assess the long-term impact of DTX401 on cornstarch requirements 
• To assess the long-term impact of DTX401 on glucose homeostasis 
• To assess the long-term impact of DTX401 on the subject's health-related quality of 
life (HRQoL) and sleep quality 
• To describe the long-term immune response to AAV8 capsid proteins after IV 
administration of DTX401 
• To describe the long-term immune response to G6Pase after IV administration of 
DTX401 
• To evaluate the long-term effect of DTX401 on lactate levels  
• To evaluate the long-term effects of DTX401 on the endocrine and metabolic 
responses to fasting 

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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design and Plan 
Study 401GSDIA02 is a long-term follow-up study to evaluate the safety and efficacy of AAV8-
mediated gene transfer of G6Pase in adults with GSDIa. In Study 401GSDIA01, subjects were 
followed for 1 year after dosing with DTX401. In Study 401GSDIA02, subjects will be followed 
for at least 3 additional years (and up to 5 additional years) for a total of 4-6 years of follow-up 
after administration of DTX401. Subjects will visit the study site approximately every 13 weeks 
during the first year of Study 401GSDIA02 and then approximately every 26 weeks through the 
end of the study at Week 312 (Year 6) for safety and efficacy evaluations. A long-term disease 
monitoring program (DMP) DTX401-CL401 is planned.  Once the DMP is available to enroll, 
and after subjects reach the Week 208 visit in Study 401GSDIA02, subjects will transition to the 
DMP with Sponsor approval. 
Safety will be assessed based on adverse events (AEs), serious adverse events (SAEs), vital sign 
measurements, body weight, physical examination findings, ECG findings, documented 
symptomatic hypoglycemic events, clinical laboratory assessments (clinical chemistry, 
hematology, coagulation panel, and urinalysis), measurement of neutralizing antibody titer to 
AAV8, measurement of AAV8 binding antibody immunoglobulin G (IgG), measurement of cell-
mediated immune response to AAV8 and G6Pase, measurement of anti-G6Pase antibodies, and 
concomitant medication. 
Efficacy will be assessed for each cohort and overall based on the change from Day 0 
(Study 401GSDIA01) measurements in time to first hypoglycemic event during a controlled 
fasting challenge over time following administration of DTX401. Other efficacy assessments 
include average daily cornstarch use, glucose levels, liver imaging results, and HRQoL and sleep 
assessments. No control group will be enrolled in Study 401GSDIA02. 
All study visits and the timing of assessments are detailed in Table 1. A schematic of the study 
design is provided in Figure 2. 
Study visits will be inpatient visits to accommodate the controlled fasting challenge, or 
outpatient visits when the controlled fasting challenge is not performed per protocol. 
At Weeks 65, 91, 130, 182, and 234, every effort will be made to conduct an on-site assessment. 
However, under extenuating subject circumstances that, in the Investigator’s opinion, make an 
on-site visit not feasible, and after all reasonable measures to enable the subject's onsite visit 
have been exhausted, a home healthcare visit and/or telemedicine assessment may be conducted 
at these time points. 
Additional unscheduled visits, either on site or home healthcare/telemedicine visits, may be 
performed to monitor subject safety, especially after any changes to the subject’s diet and 
cornstarch regimen. 

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Figure 2: 
Study Design 
Visit 1 (Week 52) 
• Visit 1 (Week 52) assessments may coincide with Week 52/EOS/EW visit in Study 401GSDIA01. 
• End of study or EW assessments for Study 401GSDIA01 do not need to be repeated for this study if written 
informed consent for Study 401GSDIA02 is obtained before the Week 52/EOS or EW assessments are 
performed for Study 401GSDIA01.  
• Assessments may be performed on more than 1 day provided that all assessments are completed and results 
are available within the 7 day window. 
Follow-up: Year 2 
(~Every 13 weeks: Weeks 65, 78, 91, 104) 
• Concomitant medications, AEs, SAEs, targeted physical examination, vital sign measurements, body 
weight, clinical laboratory assessments 
• Measurement of neutralizing and IgG antibodies as well as cell-mediated immune response to AAV8 and 
anti-G6Pase antibodies (Week 104) 
• Perform liver ultrasound (Week 78 and 104) 
• Assess symptomatic hypoglycemic events 
• Assess prescribed diet/dietary intake and cornstarch (or equivalent) use 
• Assessment of glucose levels 
• Complete controlled fasting challenge and 24-hour urine collection (both at Weeks 78 and 104)  
• Administer HRQoL and sleep quality assessments 
• Endpoint Outcomes telephone interview (Week 104 only) 
Follow-up: Years 3-6 
(~Every 26 weeks: Weeks 130, 156, 182, 208, 234, 260, 286, EOS [312]) 
• Concomitant medications, AEs, SAEs, targeted and complete (Week 312 or EW) physical examination, vital 
sign measurements, body weight, clinical laboratory assessments 
• Measurement of neutralizing antibodies and IgG antibodies as well as cell-mediated immune response to 
AAV8 and anti-G6Pase antibodies (Weeks 156, 208, 260) 
• Perform liver ultrasound (Weeks 156, 208, 260, 312) 
• Assess symptomatic hypoglycemic events 
• Assess prescribed diet/dietary intake and cornstarch (or equivalent) use 
• Assessment of glucose levels 
• Complete controlled fasting challenge and 24-hour urine collection (both at visits at Weeks 156, 208, 260) 
• Perform liver MRI (Week 260, after the controlled fasting challenge is complete) 
• Administer HRQoL and sleep quality assessments 
Early Withdrawal 
• Concomitant medications, AEs, SAEs, complete physical examination, vital sign measurements, body 
weight, clinical laboratory assessments 
• Measurement of neutralizing and IgG antibodies as well as cell-mediated immune response to AAV8 and 
anti-G6Pase antibodies  
• Assess symptomatic hypoglycemic events 
• Assess prescribed diet/dietary intake and cornstarch (or equivalent) use 
• Assessment of glucose levels 
• Complete controlled fasting challenge and 24-hour urine collection 

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• Perform liver MRI (after the controlled fasting challenge is complete) 
• Administer HRQoL and sleep quality assessments 
• Endpoint Outcomes telephone interview (only if subject withdraws prior to Week 104) 
Abbreviations: AAV8 = adeno-associated virus serotype 8; AE = adverse event; EOS = end of study; EW = early 
withdrawal; G6Pase = glucose-6-phosphatase; HRQoL = health-related quality of life; IgG = immunoglobulin G; 
MRI = magnetic resonance imaging; SAE = serious adverse event. 
Note: Specified visits that include a controlled fasting challenge will require an approximate 24-hour inpatient stay 
(Visit 1, Weeks 78, 104, 156, 208, 260, and EW visit, as applicable). All other visits (Weeks 65, 91, 130, 182, 
234, 286, and 312) will be conducted on an outpatient basis (approximately 1.5 to 2 hours).  
7.1.1. 
Number of Study Sites 
This study will include up to 12 global study sites.  
7.1.2. 
Number of Subjects 
This study will include approximately 12 subjects. 
7.1.3. 
Estimated Study Duration 
7.1.3.1. 
Study Duration for Subjects 
The duration of the study for each subject is defined as the date the subject provides written 
informed consent for Study 401GSDIA02 through the Week 312 (Year 6) visit. Subjects will be 
followed in Study 401GSDIA02 for at least 3 additional years (and up to 5 additional years) for a 
total of 4-6 years after administration of DTX401 in Study 401GSDIA01. Once the DMP is 
available to enroll, and after subjects reach the Week 208 visit in Study 401GSDIA02, subjects 
will transition to the DMP with Sponsor approval. 
Specified visits (Visit 1, Weeks 78, 104, 156, 208, 260, and EW visit, as applicable) will include 
a controlled fasting challenge and will require an approximate 24-hour inpatient stay. All other 
visits (Weeks 65, 91, 130, 182, 234, 286, and 312) will be conducted on an outpatient basis 
(approximately 1.5 to 2 hours).  
7.1.3.2. 
Selection of Study Population 
Study 401GSDIA02 is an extension study of 401GSDIA01 and all subjects who received 
DTX401 in that study were eligible to participate in 401GSDIA02. 
7.1.3.3. 
Start of Study Definition 
The start of the study is defined as the first signed informed consent. 
7.1.3.4. 
Eligibility Determination Period (Visit 1 [Week 52]) 
After each subject has provided written informed consent, the Investigator or other qualified 
study site personnel will determine whether the subject is eligible for the study. This will be 
accomplished by reviewing the inclusion and exclusion criteria and completing all of the Visit 1 
(Week 52/EOS) assessments outlined in the Schedule of Events (Table 1). Visit 1 (of Study 
401GSDIA02) assessments may be performed on more than 1 day, provided that all of the 
assessments are completed and the results are available within the permitted 7-day window. 
NOTE: Assessments required for Study 401GSDIA02 that are the same as those performed 

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during the Week 52 or EW visit in Study 401GSDIA01 do not need to be repeated if written 
informed consent for Study 401GSDIA02 is obtained before the Week 52 or EW assessments are 
performed for Study 401GSDIA01. 
In the event a subject withdraws from Study 401GSDIA01 before the Week 52 visit and then 
decides to enroll into Study 401GSDIA02, the Schedule of Events for Study 401GSDIA02 will 
be adjusted to allow for a total of 5 years of safety and efficacy follow-up after DTX401 
administration. 
7.1.3.5. 
Study Completion 
The end of the study will occur when the last subject completes the Week 312 follow-up visit (or 
or Week 208 if the last subject enrolls into the DMP).  
7.1.3.6. 
Continued Access to Study Intervention after the End of Study 
DTX401 was only administered in Study 401GSDIA01. Additional safety follow up will occur 
in the DTX401 DMP. 
7.1.4. 
Subject Input into Design 
Assessments evaluated in Study 401GSDIA02 have been streamlined and modified by protocol 
amendment following feedback from patients and families collected by sites. 
7.2. 
Discussion of Study Design, Including Choice of Control Group 
This long-term follow-up study will evaluate the safety and efficacy of DTX401 administered 
during Study 401GSDIA01. Subjects will visit the study site approximately every 13 weeks 
during the first year of Study 401GSDIA02 and then approximately every 26 weeks through the 
end of the study at Week 312 (Year 6) (or Week 208 if the last subject enrolls into the DMP) for 
safety and efficacy evaluations. 
No control group will be enrolled in Study 401GSDIA02. 
7.3. 
Changes to the Protocol due to COVID-19 
Changes to the protocol or Investigational Plan to minimize or eliminate immediate hazards or to 
protect the life and well-being of research participants and/or study staff may be implemented 
without IRB/EC approval or before filing an amendment to the competent authority but are 
required to be reported afterward. Investigators should contact Ultragenyx or designee to 
determine an appropriate course of action, which may include but is not limited to remote visits, 
home health visits, and out of window visits or assessments.  Any changes to the protocol or 
investigational plan must be documented. The Investigator will work with Ultragenyx or 
Designee and IRB/EC to prioritize reporting of protocol deviations that impact safety of trial 
participants.  
In response to COVID-19 travel restrictions, patients may be monitored remotely in place of a 
scheduled in-clinic visit or an unscheduled safety visit between study visit time points. To limit 
unnecessary and potentially unsafe travel to the clinical site, Ultragenyx will provide the means 
for the Investigator to arrange home visits for collection of lab samples as necessary. A qualified 
healthcare professional from Firma Clinical Research, trained in the study and its procedures, 

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will be dispatched to collect samples on behalf of the Investigator. These home health visits will 
be documented as an unscheduled safety visit in the subject’s source and recorded as such in the 
electronic case report form (eCRF). The Investigator may arrange home visits for collection of 
lab samples as clinically indicated or in response to COVID-19 related travel restrictions. Any 
missed scheduled clinic visits or assessments caused by COVID-19 travel restrictions will be 
entered as COVID-19 Protocol Deviations.  

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8. 
STUDY POPULATION 
All subjects enrolled in Study 401GSDIA02 will have received a single IV dose of DTX401 
during their participation in Study 401GSDIA01.  
Information about the study population size is provided in Section 7.1.2. 
8.1. 
Inclusion Criteria 
Individuals eligible to participate in this study must meet all of the following criteria:  
1. Received DTX401 in Study 401GSDIA01 
2. Willing and able to provide written informed consent after the nature of the study has 
been explained, and prior to any research-related procedures being performed 
3. Willing and able to comply with all scheduled study visits, procedures, and requirements 
8.2. 
Exclusion Criteria 
Individuals who meet any of the following exclusion criteria will not be eligible to participate in 
the study: 
1. Planned or current participation in any other interventional clinical study that may 
confound the safety or efficacy evaluation of DTX401 during this study 
2. Presence or history of any condition that, in the view of the Investigator, poses a risk to 
subject safety or places the subject at high risk of poor compliance or not completing the 
study or that would significantly affect the interpretation of study results 
8.3. 
Removal of Subjects from Therapy or Assessment 
In accordance with the Declaration of Helsinki, subjects have the right to withdraw from the 
study at any time for any reason. The Investigator and Ultragenyx also have the right to remove 
subjects from the study. Ultragenyx must be notified of all subject withdrawals as soon as 
possible. 
Subjects may be removed from the study for the following reasons: 
• A condition or illness that, in the judgment of the Investigator, might place the subject 
at risk or interfere with study participation 
• Subject withdrawal of consent 
• Lost to follow up 
• Death 
Any subject who experiences an unexpected and DTX401-related SAE (Sections 11.1.1 and 
11.1.3) that represents a change in the severity or an increase in frequency of the event from their 
prior medical history or known GSDIa-related medical issues will be evaluated as to whether the 
subject will continue on the study. 
If the reason for removal of a subject from the study is an AE, the AE and any related test or 
procedure results will be recorded in the source documents and transcribed onto the eCRF. Each 

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related clinically significant abnormal laboratory value or other clinically meaningful 
abnormality should be followed until the abnormality resolves or until a decision is made that it 
is not likely to resolve. All unscheduled tests must be reported to Ultragenyx immediately.  
If a subject discontinues from the study prematurely, every reasonable effort should be made to 
perform the EW Visit procedures within 1 week of discontinuation. 

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9. 
TREATMENTS 
9.1. 
Investigational Product 
No IP will be administered during this study.  
9.2. 
Reference Therapy 
Not applicable.  
9.3. 
Dosage Administration 
Not applicable. 
9.4. 
Dosage Rationale 
Not applicable. 
9.5. 
Concomitant Medications, Therapies, and Procedures 
Subjects may receive concomitant medications, therapies, and procedures as required, with the 
exception of those identified in Section 9.6 as prohibited. Medications (investigational, 
prescription, over-the-counter, and herbal) and nutritional supplements taken during the 30 days 
prior to enrollment or Visit 1 will be reviewed and recorded at enrollment or Visit 1. At Visit 1 in 
Study 401GSDIA02, current medications will be recorded. At each visit, any concomitant 
medications added or discontinued during the study should be recorded on the eCRF. 
The site personnel should record the following in the eCRF: date the medication was taken, the 
name of the medication, medication dosage, and the reason the medication was taken. This 
includes all prescription drugs, herbal products, vitamins, minerals, and over the counter 
medications. Any changes in concomitant medication use will also be recorded in the subject’s 
eCRF. The minimum requirement for therapies and procedures is to record the name and date of 
the therapy or procedure and the reason it was performed. 
9.6. 
Restricted or Prohibited Medications, Devices, and Procedures 
The following are specifically prohibited during study participation: 
• Any IP 
• Any gene therapy product 
9.7. 
Treatment Compliance 
Not applicable.  
9.8. 
Treatment Group Allocation 
9.8.1. 
Method of Assigning Subjects to Treatment Groups 
As no IP is administered in this study, there will be no assignment to treatment groups. Subject 
numbers will remain the same as those assigned in Study 401GSDIA01.  

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9.8.2. 
Blinding 
Not applicable. 

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10. 
STUDY PROCEDURES  
10.1. 
Study Schedule 
Parameters to be assessed and the timing of assessments are provided in Table 1. 
10.2. 
Informed Consent and Eligibility Requirements 
Written informed consent for participation in the study must be obtained before performing 
any study specific tests or evaluations. 
Informed consent forms (ICFs) for enrolled subjects and for subjects who are not subsequently 
enrolled will be maintained at the study site. 
The Investigator will maintain a screening log to record details of all subjects screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
10.3. 
Safety Assessments 
Safety will be evaluated by the incidence, frequency, and severity of AEs and SAEs, and by vital 
sign measurements, body weight, complete and targeted physical examination findings, 
electrocardiogram (ECG) results, documented hypoglycemia events, clinical laboratory 
evaluations (clinical chemistry including liver function tests [LFTs], hematology, coagulation 
panel, and urinalysis), measurement of neutralizing antibodies to AAV8, measurement of AAV8 
binding antibody IgG, measurement of anti-G6Pase antibodies, measurement of cell-mediated 
immune response to AAV8 and G6Pase, and concomitant medications.  
10.3.1. 
Adverse Events 
All AEs will be recorded from the time the subject signs the ICF and up to the end of study 
(EOS; Week 312 or Week 208 if the last subject enrolls into the DMP) or Early Withdrawal visit. 
Serious AEs will be recorded for up to 30 days after the EOS or Early Withdrawal visit. The 
determination, evaluation, reporting, and follow up of AEs will be performed as outlined in 
Section 11. At each visit, subjects will be asked about any new or ongoing AEs since the 
previous visit. Assessments of AEs will occur at each study visit.  
Clinically significant changes from Visit 1 will be recorded as AEs or SAEs, if appropriate.  
10.3.2. 
Vital Sign Measurements 
Vital signs to be measured will include heart rate in beats per minute, seated systolic blood 
pressure and diastolic blood pressure measured in millimeters of mercury (mm Hg), and 
respiration rate in breaths per minute. Vital signs measurements will be performed at every visit 
before any additional assessments are completed.  
Vital sign measurements will be recorded on the appropriate page of the eCRF. The medical 
monitor should be notified of any clinically significant changes or abnormal value in vital sign 
measurements (Section 11.1). If, in the medical and scientific judgment of the Investigator, a 
clinically significant change or abnormal vital sign measurement is observed, it should be 
recorded as an AE or SAE, as defined in Section 11.1, on the appropriate pages of the eCRF. 

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10.3.3. 
Body Weight 
Body weight will be assessed at the time points specified in the Schedule of Events (Table 1).  
10.3.4. 
Physical Examinations  
A complete or targeted physical examination will be performed at the time points specified in the 
Schedule of Events (Table 1). 
A complete physical examination will include assessments of the head, eyes, ears, nose, and 
throat; skin; abdomen with documentation of liver and spleen size; and the endocrine, metabolic, 
neurological, respiratory, cardiovascular, gastrointestinal, and musculoskeletal systems. 
A targeted physical examination will include assessment of the skin, the abdomen with 
documentation of liver and spleen size, and the respiratory, cardiovascular, gastrointestinal, and 
peripheral and central nervous systems. 
Physical examination findings will be captured on the appropriate page of the eCRF. 
10.3.5. 
Electrocardiograms 
An ECG will be performed at Visit 1 (Table 1). A single 12-lead ECG will be obtained using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
corrected QT intervals.  
Twelve-lead ECGs should be measured with the subject having rested for at least 5 minutes 
beforehand. It is preferred that the measurement be late with the subject rested, rather than on 
time with the subject not sufficiently rested. If the subject is not sufficiently rested, this needs to 
be stated in the source documents. Electrocardiogram results will be recorded on the appropriate 
page of the eCRF. 
10.3.6. 
Hypoglycemic Events 
At each visit, the study site will instruct subjects on proper glucose monitoring at home, the signs 
and symptoms of hypoglycemia, and supplemental glucose treatment if needed. During each 
visit, the study site will record the number of symptomatic hypoglycemia events in the eCRF. 
10.3.7. 
Clinical Laboratory Tests 
The clinical laboratory evaluations to be performed in this study include clinical chemistry 
(including LFTs), hematology, coagulation panel, and urinalysis. Clinical laboratory testing will 
be performed at the time points specified in the Schedule of Events (Table 1). Fasting is not 
required. 
Laboratory tests, including ALT, will be closely monitored throughout the duration of the study. 
Investigators will receive flagged notification of any laboratory values that are outside of the 
normal range. Any abnormal laboratory test results, including those that worsen from Visit 1 or 
are considered to be clinically significant in the medical and scientific judgment of the 
Investigator, are to be recorded as AEs or SAEs (Section 11.1). 
Blood, saliva, urine, and stool samples for vector shedding will only be collected for subjects 
who did not demonstrate clearance in Study 401GSDIA01. Samples for vector shedding analysis 
will be collected until at least 3 consecutive negative results are obtained for each sample matrix.   

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However, any clinically significant safety assessments that are associated with GSDIa are not to 
be reported as AEs, unless they are judged by the Investigator to be more severe than expected 
for the subject’s condition. 
All laboratory tests with results that are significantly abnormal during participation in the study 
should be repeated until the values return to normal or Visit 1 values. If such values do not return 
to normal within a period judged reasonable by the Investigator, the etiology should be identified 
and the Sponsor notified. 
The clinical laboratory evaluations to be performed in this study are listed in Table 2. In addition 
to these clinical laboratory evaluations, glucose and lactate venous blood samples will be 
obtained as described in Sections 10.4.1 and 10.3.7.1, respectively.  
Table 2: 
Clinical Laboratory Parameters 
Clinical chemistry: 
Lipid panel, uric acid, sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, 
creatinine, glucose, calcium, phosphate, magnesium, albumin, total protein, creatine 
kinase, bilirubin (total, direct, and indirect), ALT, AST, ALP, gammaglutamyl transferase, 
and lactate dehydrogenase 
Clinical chemistry 
(other):1 
Glucose and lactate 
Hematology: 
Complete blood count with differential 
Urinalysis: 
Specific gravity, pH, glucose, protein, blood (by dipstick), ketones (by dipstick), and 
microscopic examination (if blood or protein is found) 
Coagulation panel: 
PT/INR and aPTT 
Other: 
Cortisol, ACTH, free fatty acids, glucagon, insulin, C-peptide, growth hormone, IGFBP1, 
alanine and ketone levels (3-hydroxy butyrate), AAV8 neutralizing antibody, 
AAV8 binding antibody IgG, , cell-mediated immune response to AAV8 and G6Pase, 
anti-G6Pase antibody, vector genome, vector shedding2 
Abbreviations: AAV = adeno-associated virus; ACTH = adrenocorticotropic hormone; ALP = alkaline phosphatase; 
ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; G6Pase, glucose6phosphatase; IGFBP1 = insulin-like growth factor-binding protein 1; 
PT/INR = prothrombin time/international normalized ratio. 
1  Samples collected during the controlled fasting challenge should be sent to the local laboratory (STAT samples) 
for analysis. 
2 Samples for vector shedding will only be collected for subjects who do not show clearance in Study 401GSDIA01 
Details for the preparation and shipment of samples will be provided by the central or specialty 
laboratory. Reference ranges for all parameters will be provided to the study site by the central or 
specialty laboratory. 
Subjects who experience an SAE or other AE of concern may, at the discretion of the 
Investigator (and/or medical monitor), have additional blood samples taken for safety laboratory 
tests. 
10.3.7.1. Lactate 
Lactate levels will be measured during the controlled fasting challenge (Section 10.4.1) at the 
time points specified in the Schedule of Events (Table 1). A blood sample for venous lactate will 
be collected through an indwelling catheter (central or peripheral) at the beginning of the 
controlled fasting challenge and approximately every 60 minutes (±5 minutes) until glucose 

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levels are at or below 70 mg/dL (≤3.9 mmol/L). Once glucose levels are at or below 70 mg/dL 
(≤3.9 mmol/L), a blood sample for lactate will be collected approximately every 30 minutes 
(±5 minutes) until the subject’s glucose level drops below 54 mg/dL (<3.0 mmol/L), the subject 
experiences symptoms of hypoglycemia per the Investigator’s discretion, or the fast reaches 
15 hours without hypoglycemia, whichever occurs first. 
Lactate samples should be sent to the local laboratory (STAT sample) and results should be 
available within 30 minutes or less of the blood collection. Samples should be prepared and 
transported to the local laboratory in accordance with the site’s standard procedures. 
10.3.7.2. Other Controlled Fasting Challenge Laboratory Assessments 
Blood samples for measurement of cortisol, ACTH, free fatty acids, glucagon, insulin, C-peptide, 
growth hormone, IGFBP1, alanine and ketone levels (3-hydroxy butyrate) will be collected at the 
beginning and end of the controlled fasting challenge, or more frequently at the Investigator’s 
discretion, if possible (Section 10.4.1). Details for the preparation and shipment of samples are 
included in the laboratory manual. 
10.3.7.3. 24-Hour Urine Collection 
The excretion of total protein, microalbumin, and creatinine in the urine will be determined over 
a 24-hour period. Timed 24-hour complete urine samples will be collected at the time points 
specified in the Schedule of Events (Table 1). 
10.3.8. 
Adeno-Associated Virus Serotype 8 Binding Antibody Immunoglobulin G Assay 
Blood samples for the AAV8 binding antibody IgG assay will be collected at the time points 
specified in the Schedule of Events (Table 1) to monitor for circulating anti-AAV8 antibodies. 
The assay will be performed using a research method (enzyme-linked immunosorbent assay 
[ELISA]). 
10.3.9. 
Neutralizing Antibodies to AAV8 
Blood samples for determination of neutralizing antibodies to AAV8 will be collected at the time 
points specified in the Schedule of Events (Table 1) to monitor for a humoral immune response 
to AAV8. The assay will be performed using a research method (cell-based assay). 
10.3.9.1. Cell-Mediated Immune Response 
The presence of T cells specific for AAV8 and G6Pase will be determined by an enzyme-linked 
immunospot (ELISPOT) assay. A blood sample will be collected at the time points specified in 
the Schedule of Events (Table 1). 
10.3.10. 
Anti-Glucose-6-Phosphatase Antibody Assay 
Blood samples for the anti-G6Pase antibody assay will be collected at the time points specified 
in the Schedule of Events (Table 1) to monitor for circulating anti-G6Pase antibodies. The assay 
will be performed using a research method. 

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10.3.11. 
Vector Shedding 
In the event that clearance was not observed for vector shedding for a subject in Study 
401GSDIA01, then blood, saliva, urine, and stool samples will be collected at the time points 
specified in the Schedule of Events (Table 1) to monitor for vector shedding. The presence of 
DTX401 will be determined by quantitative polymerase chain reaction (qPCR). Samples for 
vector shedding analysis will be collected until at least 3 consecutive negative results are 
obtained for each sample matrix. 
10.3.12. 
Pregnancy Testing and Contraception Requirements 
Pregnancy testing and contraception use are not required for this study.  
Refer to Section 11.1.4.3 for pregnancy reporting requirements. 
10.4. 
Disease-Specific Clinical Assessments 
10.4.1. 
Symptom-Free Euglycemia (Controlled Fasting Challenge) 
The subject's ability to maintain symptom-free euglycemia during a controlled fasting challenge 
will be assessed at specified time points (Table 1). However, if clinically indicated, the 
controlled fasting challenge can be performed at an unscheduled visit.  
The controlled fasting challenge requires a 24-hour inpatient stay in a hospital or research facility 
and will be performed after all other study visit assessments (except MRI, if applicable) have 
been completed and the required laboratory assessments (as specified below) have been reviewed 
by the Investigator (or a subinvestigator assigned to review results and make clinical decisions 
per the site delegation log). Subjects should wear their continuous glucose monitoring (CGM) 
device throughout the fasting challenge, and should not change the sensor prior to the 
assessment.  
Before the controlled fasting challenge begins, the study site will provide dinner for the subject. 
The dinner meal will be personalized for each subject, and will include a target carbohydrate 
range and overall composition in protein, fats and dietary fibers that is as close as possible to the 
subject’s most current dinner prescription, but not higher in carbohydrate content than the dinner 
prescription recorded at their baseline visit in Study 401GSDIA01. The start and stop time of the 
dinner meal and its full dietary composition including amount of carbohydrates consumed will 
be recorded. After dinner, subjects will be given an oral dose of cornstarch equivalent per their 
most recent cornstarch prescription, at approximately the same time that they typically take it, 
but no later than 3 hours post dinner. The amount of cornstarch administered should not be 
higher than the prescribed amount recorded at their baseline visit in Study 401GSDIA01. The 
time of ingestion of prefasting cornstarch and the amount consumed will be recorded. After the 
cornstarch is ingested, the controlled fasting challenge will begin, and the start time will be 
recorded accordingly. If a subject does not receive cornstarch before going to bed at the time of 
the CFC, the fasting challenge will start after they complete their dinner. Subjects will be 
instructed to minimize activity after they finish eating dinner until the end of the controlled 
fasting challenge. 
During the fast, subjects may not ingest any food or drink other than water. The controlled 
fasting challenge will end when the subject’s glucose level decreases to < 54 mg/dL 

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(< 3.0 mmol/L) or when the subjects experience signs and symptoms of hypoglycemia, or when 
the fast reaches 15 hours without hypoglycemia, whichever occurs first. The stop time of the 
controlled fasting challenge will be recorded. At the end of the controlled fasting challenge, the 
subject’s hypoglycemia should be treated per the institution’s standard procedure, which may 
include providing the subject with a meal, cornstarch, or IV glucose, if medically indicated.  
In cases where the controlled fasting challenge is terminated prematurely before the subject 
reaches a glucose level of < 54mg/dL or without the subject experiencing signs and symptoms of 
hypoglycemia, or due to any deviation in the fasting challenge protocol, an ad hoc fasting 
challenge may be scheduled within 6 weeks from the scheduled fasting challenge.  
Laboratory sample collection before and during the controlled fasting challenge 
On the morning of inpatient visit for the controlled fasting challenge, after vital signs and other 
non-interventional assessments have been performed, samples will be collected for standard 
clinical chemistry (including lipid levels), hematology, coagulation panel, and urinalysis. These 
samples should be collected at least 2 to 4 hours after the subject’s last meal and sent to the 
central lab. A sample for STAT AST and ALT level analysis will also be collected at this time 
and sent to the local laboratory; the Investigator or delegated subinvestigator should review the 
results before starting the controlled fasting challenge. 
Total urine voided over the 24-hour period starting at the time of inpatient admission will be 
collected during the controlled fasting challenge.  
Blood samples for measurement of cortisol, ACTH, free fatty acids, glucagon, insulin, C-peptide, 
growth hormone, IGFBP1, alanine and ketone levels (3-hydroxy butyrate) will be collected at the 
beginning (ie, immediately after the post-dinner dose of cornstarch, or immediately after dinner 
for subjects who do not take a post-dinner dose of cornstarch) and end of the controlled fasting 
challenge, or more frequently at the Investigator’s discretion. A final sample for glucose, lactate, 
growth hormone, IGFBP1, ACTH and cortisol measurement will be collected 30 minutes after 
the end of the controlled fasting challenge. Samples should be prepared and transported to the 
local laboratory in accordance with the site’s standard procedures. 
Blood samples for STAT analysis of glucose and lactate will be collected through an indwelling 
catheter (central or peripheral) at the following time points: 
• At the beginning of the fast (ie, immediately after the post-dinner dose of cornstarch, or 
immediately after dinner for subjects who do not take a post-dinner dose of cornstarch) 
• Approximately every 60 minutes (± 5 minutes) until the glucose level decreases to 
≤ 70 mg/dL (≤ 3.9 mmol/L) 
• Approximately every 30 minutes (± 5 minutes) until the glucose level decreases to 
< 54 mg/dL (< 3.0 mmol/L) or when the subjects experience signs and symptoms of 
hypoglycemia, or when the fast reaches 15 hours without hypoglycemia, whichever occurs 
first 
Samples should be prepared and transported to the local laboratory in accordance with the site’s 
standard procedures. To ensure the safety of the study subjects, results from these tests should be 
available within 30 minutes after the blood sample collection. Capillary glucose will be 
performed at the same time points as blood samples for STAT analysis of glucose and lactate. 

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Results of the capillary glucose and readings from CGM at corresponding time points will be 
noted on a controlled fasting challenge results sheet. 
10.4.2. 
Continuous Glucose Monitoring 
Supplemental information on glucose level trends will be collected using a CGM device. If 
subjects do not already have a study-issued CGM device (as these are provided in Study 
401GSDIA01), a study-issued CGM will be provided. Subjects should bring their CGM device 
to each visit, containing CGM data from the 28 days prior to the visit (Table 1). If a study visit is 
conducted remotely (home healthcare visit or telemedicine), or if a study visit is skipped entirely 
for any reason, arrangements will be made for the subject to ship the CGM receiver (ideally, 
containing CGM data from the 28 days prior to the remote/missed visit) to the clinical site. 
Data from the subject’s CGM device will be transferred to the Sponsor throughout the study, 
including a final data transfer at the end of the Week 312 visit or early withdrawal. It is 
recommended that all CGM sensors should be paired with the study-issued receiver, regardless 
of whether the subject is also paring the sensor with their own personal device (i.e. smartphone).  
The receivers should be maintained in bluetooth range of the sensors, whenever possible, and the 
data from the receivers should be uploaded on the study-issued laptop on a weekly basis.  
Additional details regarding the care and use of the CGM device and sensors and data transfer to 
the Sponsor are provided in the Manual of Operations. 
10.4.3. 
Morning Glucose Assessments 
If a subject is unable to use the assigned CGM, the subject should collect morning glucose levels 
at least 2 mornings per week throughout the study (Table 1). Subjects should adhere to their 
prescribed overnight cornstarch diet. Morning glucose levels should be measured using the 
subject’s own glucose monitoring device before taking their morning dose of cornstarch. The 
collection time, glucose level, and prior day’s overnight cornstarch use should be collected on 
the Morning Glucose Level monitoring worksheet provided by the site. Subjects should bring the 
completed worksheets to each study visit. Data collected on the worksheet will be captured on 
the appropriate page of the eCRF. 
10.4.4. 
Magnetic Resonance Imaging  
An MRI of the liver will be conducted at the time points specified in the Schedule of Events 
(Table 1). The MRI should be completed after the controlled fasting challenge to avoid having to 
replace the CGM sensor prior to the fasting challenge. Magnetic resonance imaging will be 
conducted at the study site; however, all results will be transmitted to a central radiologist for 
interpretation to ensure consistent assessment across study sites. Instructions for transmitting 
MRI results will be provided separately. Magnetic resonance imaging results will be analyzed for 
hepatic fat fraction, liver volume, and the relative change in each from Study 401GSDIA01 
Baseline (Day 0). 
Completion of the MRI will be recorded on the appropriate page of the eCRF. At the end of the 
study, images may be stored for up to 15 years and analyzed to better understand the effect of 
DTX401 on GSDIa or other metabolic deficiencies. The choice to allow retention and future 
analysis will be optional. 

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10.4.5. 
Liver Ultrasound  
An ultrasound of the liver will be conducted at the time points specified in the Schedule of 
Events (Table 1). The ultrasound should be completed prior to the controlled fasting glucose 
challenge. The liver ultrasound will be conducted at the study site and analyzed for liver volume. 
10.5. 
Biomarker Assessments 
Not applicable.  
10.6. 
Patient-Reported and Clinician-Reported Outcomes 
10.6.1. 
Health-Related Quality of Life and Sleep Quality Assessments 
Subjects will be asked to complete the following HRQoL and sleep quality assessments 
(Table 1).  
• Patient-Reported Outcomes Measurement Information System (PROMIS®)-29 
(Appendix 1) 
• PROMIS Social Isolation (Appendix 2) 
• Pittsburgh Sleep Quality Index (Appendix 3)  
• Patient Global Impression of Severity (Appendix 4) 
• Patient Global Impression of Change (Appendix 5) 
Subjects will complete the HRQoL and sleep quality assessments prior to invasive assessments 
being conducted. Subjects may pause to rest during administration of the HRQoL and sleep 
quality assessments, but the entire set of assessments should be completed in 1 session. Study 
staff should review the completed forms for completeness once the subject returns the forms to 
staff. 
Data collected on the HRQoL and sleep quality assessments will be captured on the appropriate 
page of the eCRF. 
10.6.2. 
Endpoint Outcomes Interview (Year 2 – Exit Interview) 
A 30-minute scripted telephone interview will be conducted at Week 104 (or at Early 
Withdrawal, if the subject withdraws prior to Week 104) to better quantify the subject experience 
in the study. The interview will be conducted by a third-party vendor, Endpoint Outcomes, 
specializing in the capture of caregiver and subject-reported data. Endpoint Outcome uses a 
script as an interview guide to serve as a basis for the discussion. The interview will be 
conducted by phone.  
The subject has consented to the interview per the study’s main ICF. However, prior to the start 
of the interview, Endpoint Outcomes will verbally ask for the subject’s consent for the interview 
to be audio-recorded. With the subject’s verbal consent, the interview will be audio-recorded, 
and the interviewer will proceed through a script. If the subject does not give permission for the 
session to be audio-recorded, the interview will not proceed. Subjects will be asked about their 
experience in the study. They may refuse to answer any question in the interview and may stop at 
any time.  

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Site staff will facilitate the phone call so that the subject’s contact information remains 
anonymous. Personal information (including subject’s name and telephone number) will remain 
anonymous and will not be provided to the Sponsor or Endpoint Outcomes. Subjects will be 
identified only by their study specific subject IDs.  
All digital recordings will be stored by Endpoint Outcomes in a secure place where only 
Endpoints Outcome personnel directly related to this study will be able to access it. The audio 
interviews will be transcribed by a transcription company under contract and a confidentiality 
agreement, who will provide the written transcripts that will be further analyzed by Endpoint 
Outcomes. The transcription company is also contracted to ensure that transcripts will not 
contain any personal identifying information (eg, reference of first names) that may have been 
revealed during the interview process; personal identifying information will be removed and will 
not appear in the final transcript. Data from the interview will be shared with the Sponsor only 
after all identifying information has been removed. 
10.7. 
Pharmacokinetic Assessments 
Not applicable.  
10.8. 
Other Assessments 
10.8.1. 
Demographic and Medical History Assessments 
As allowed by local laws and regulations, the following demographic data may be captured on 
the appropriate page in the eCRF: date of birth, sex, race, and ethnicity.  
Medical history will be assessed at Visit 1 (Table 1). Any AEs that are ongoing at the completion 
of Study 401GSDIA01 will be considered medical history in Study 401GSDIA02.  
10.8.2. 
Assessment of Prescribed Diet and Dietary Intake 
The subject’s prescribed diet will be reviewed at each study visit, and if possible, on a monthly 
basis through the final study visit (Table 1). Content, quantity, and frequency of diet intake 
(including daily carbohydrate intake) will be recorded on the appropriate page of the eCRF. 
10.8.3. 
Assessment of Cornstarch (or Equivalent) Use 
The subject’s average daily use of cornstarch (or equivalent) will be reviewed at each study visit, 
and if possible, on a monthly basis through the final study visit (Table 1). Follow-up phone calls 
may occur regularly (approximately once a month) to further discuss if adjustments are needed 
for a subject’s cornstarch use. Quantity and frequency of intake will be recorded on the 
appropriate page of the eCRF. 
10.9. 
Appropriateness of Measurements 
All measurements will be performed using standard methods that are generally recognized as 
reliable, accurate, and relevant. 

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11. 
SAFETY DATA COLLECTION, RECORDING, AND 
REPORTING 
11.1. 
Reporting and Follow-up of Adverse Events 
11.1.1. 
Adverse Event Terminology 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) products. 
An SAE is an AE that at any dose, in the view of either the Investigator or Sponsor, results in 
any of the following serious outcomes:  
• Death 
• A life-threatening AE 
• A life-threatening AE is an event that, in the view of either the Investigator or 
Sponsor, places the patient or subject at immediate risk of death. It does not include 
an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Note that hospitalizations planned prior to study enrollment (eg, for elective 
surgeries) are not considered SAEs; however, an event that prolongs this type of 
hospitalization would be considered an SAE. Hospitalizations that occur for pre-
existing conditions that are scheduled after study enrollment are considered SAEs. 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be immediately life-
threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in the 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse 
Nonemergent hospitalization for cornstarch management will not be considered an SAE. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug 
caused the AE. For the purposes of expedited safety reporting, “reasonable possibility” means 
there is evidence to suggest a causal relationship between the drug and the AE. Suspected 

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adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which 
means any AE caused by a drug. 
As there is limited prior clinical experience with DTX401, reference safety information for 
assessing whether an AE is a suspected unexpected serious adverse reaction (SUSAR) is 
currently not available. Therefore, any SAE considered related to DTX401 will be considered a 
SUSAR and reported immediately. The SAE should be treated with appropriate supportive and 
medical care deemed necessary for the well-being of the subject.  
11.1.2. 
Severity of Adverse Events 
The severity/toxicity, or intensity, of an AE refers to the extent to which an AE affects the 
subject’s daily activities. The Investigator should rate the intensity of an AE as Grade 1, 2, 3, 4, 
or 5 based on their medical judgment. The most current version of the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI, 2018) can be used to guide the rating 
of an AE.  
In the event that an AE occurs during the study that is not captured by the CTCAE, the AE 
should be graded according to the general guidelines outlined in Table 3. 
Table 3: 
General Guidelines for Grading Events Not Captured by the CTCAE 
Grade 
Criteria 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL.1 
Grade 3 
Severe or medically significant but not immediately life threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL.2 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Abbreviations: ADL = activities of daily living; AE = adverse event; CTCAE = Common Terminology Criteria for 
Adverse Events. 
1 Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
2 Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
Changes in the severity/toxicity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized as 
intermittent do not require documentation of onset and duration of each episode. 
Terminology Clarification: The term “severe” is often used to describe the intensity (severity) 
of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, 
however, may be of relatively minor medical significance (such as severe headache). The 
severity is not the same as “serious” which is based on subject/event outcome or action criteria 
and is usually associated with events that pose a threat to a subject's life or functioning 
(Section 11.1.1). Seriousness (not severity) serves as a guide for defining regulatory reporting 
obligations (Section 11.1.4.2). 

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11.1.3. 
Relationship of Adverse Events to Investigational Product 
The Investigator will assess the potential relationship of the AE to IP using the following 
descriptions.  
Categories of attributions for “unrelated” events: 
• Unrelated: This category applies to an AE that is clearly not related to the 
investigational agent/procedure. 
Categories of attributions for “related” events: 
• Possibly Related: This category applies to an AE that may be related to the 
investigational agent/procedure. 
• Probably Related: This category applies to an AE that is likely related to the 
investigational agent/procedure.  
• Definitely Related: This category applies to an AE that is clearly related to the 
investigational agent/procedure. 
For the purposes of reporting to regulatory agencies, AEs deemed as definitely, probably or 
possibly related will be considered related. 
11.1.4. 
Adverse Event Reporting 
11.1.4.1. General 
All AEs (ie, any new condition or worsening in severity or frequency of a preexisting condition) 
with onset after the subject signs consent for study participation must be promptly documented 
on the eCRF. The Investigator is responsible for evaluating all AEs, obtaining supporting 
documents, and ensuring documentation of the events is adequate. Details of the AEs must 
include severity, relationship to IP, duration, and outcome.  
All AEs will be collected from the time the subject signs the ICF and up to the EOS (Week  312 
or Week 208 if the last subject enrolls into the DMP) or Early Withdrawal visit. In addition, the 
Investigator should report any AE they are made aware of that occurs after this time period and 
that is believed to have a reasonable possibility of being associated with IP. Serious AEs will be 
recorded for up to 30 days after the EOS or Early Withdrawal visit.  
Any AEs ongoing at 30 days following the EOS visit or Early Withdrawal visit should have a 
comment in the source document by the Investigator that the event has recovered, recovered with 
sequelae, or stabilized.  
11.1.4.2. Requirements for Immediate Reporting of Serious Adverse Events and Serious 
Adverse Drug Reactions 
Ultragenyx or its designee must be notified of the occurrence of any SAE that occurs during the 
reporting period within 24 hours of the Investigator, designee, or site personnel’s knowledge of 
the event. The study site should record all SAE information on the SAE page in the eCRF and 
submit the report via the electronic data capture (EDC) system. In the event of any fatal or life-
threatening SAE, the Investigator must immediately inform Ultragenyx or its designee by 
telephone and report the SAE in the EDC system. If, for any reason, it is not possible to report 

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the SAE in the EDC system (eg, the EDC system is unavailable), the study site should record the 
SAE on the paper SAE Reporting Form and submit it by fax or email. As soon as it is possible, 
any SAE reported via fax must be entered into the EDC system. See Section 11.4 for contact 
information for SAE reporting. 
Follow-up SAE information must be submitted in a timely manner as additional information 
becomes available. All SAEs regardless of relationship to IP must be followed to resolution or 
stabilization if improvement is not expected.  
All deaths, regardless of causality, occurring from the time the subject signs the ICF until 
30 days following the EOS (Week 312 or Week 208 if the last subject enrolls into the DMP) or 
Early Withdrawal visit are to be reported as SAEs to Ultragenyx or its designee within 24 hours 
of knowledge.  
11.1.4.3. Requirements for Reporting of Pregnancy in Subject or Partner 
Ultragenyx or its designee must be notified of the occurrence of any pregnancy in a subject or 
subject’s partner that occurs during the reporting period within 2 weeks of the Investigator, 
designee, or site personnel’s knowledge of the event. Pregnancies must be reported by 
completing and submitting the paper Pregnancy Report Form to Ultragenyx or designee by fax. 
See Section 11.4 for contact information for pregnancy reporting.  
Any reported pregnancy of a subject or a subject’s partner that occurs during participation in the 
study will be monitored for the full duration of the study and/or followed until the outcome of 
the pregnancy is known. In the event of a pregnancy in the partner of a subject, the Investigator 
should make every effort to obtain the female partner’s consent for release of protected health 
information. 
Ultragenyx or its designee must be notified of the outcome of the pregnancy within 2 weeks of 
the Investigator, designee, or site personnel’s knowledge of the outcome. Pregnancy outcomes 
must be reported by completing and submitting the paper Pregnancy Report Form to Ultragenyx 
or designee by fax. All neonatal deaths that occur within 28 days of birth should be reported as 
an SAE. 
Pregnancy-associated SAEs will be processed and submitted, as necessary, per the suspected 
unexpected serious adverse reaction (SUSAR) reporting process indicated in Section 11.1.5.1. 
11.1.5. 
Safety Communication Plan 
11.1.5.1. Serious Adverse Drug Reaction Reporting 
Ultragenyx or its designee will submit SUSARs to appropriate Regulatory Authorities (including 
Competent Authorities in all Member States concerned), Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs), and Investigators as per local laws and 
regulations. Fatal and life-threatening SUSARs will be submitted no later than 7 calendar days of 
first knowledge of the event and follow-up information submitted within an additional 8 days. 
All other SUSARs will be submitted within 15 calendar days of first knowledge of the event.  
The Investigator will notify the IRBs/IECs of SAEs, in accordance with IRB/IEC requirements 
and local laws and regulations. A copy of this notification must be provided to Ultragenyx or its 
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11.1.5.2. Urgent Safety Matters and Non-SUSAR Reporting 
Investigators are required to report any urgent safety matters to Ultragenyx or its designee within 
24 hours. Ultragenyx or its designee will inform the Regulatory Authorities, IRBs/IECs, and 
other Investigators of any events (eg, change to the safety profile of DTX401, major safety 
findings) that may occur during the clinical study that do not fall within the definition of a 
SUSAR but may affect the safety of subjects participating in the clinical study, as required, in 
accordance with applicable laws and regulations. The reporting period for urgent safety issues is 
the period from the signing of the ICF through 30 days following the EOS or Early Withdrawal 
visit. 
The Investigator will notify the IRBs/IECs of urgent safety matters, in accordance with IRB/IEC 
requirements and local laws and regulations. A copy of this notification must be provided to 
Ultragenyx or its designee. 
Non-SUSARs will be maintained in the PPD safety database and provided in annual safety 
reports and/or other aggregate periodic summary reports to Regulatory Authorities and 
IRBs/IECs per local laws and regulations.  
11.2. 
Safety Data Monitoring 
There will not be a Data Monitoring Committee in this study.  
Potential safety signals identified during routine monitoring by the PPD Medical Monitor and 
Ultragenyx during the conduct of the study will be escalated to the appropriate internal 
Ultragenyx safety governing bodies. Any action indicated by Ultragenyx safety governing bodies 
will be communicated accordingly to all stakeholders, eg, Regulatory Authorities, IRBs/IECs, 
and Investigators. 
11.3. 
Study Termination or Suspension Due to Safety Events 
Should an unexpected and IP-related SAE occur, the IRB/IEC and appropriate regulatory 
authorities will be informed per local laws and regulations (Section 11.1.5.1). A full evaluation 
of the event will be performed to make a decision regarding what actions to take, including 
whether to recommend stopping the study.  
Regulatory Authorities, as well as IRBs/IECs, will be informed if the study is paused or stopped. 
If the Sponsor deems it appropriate to restart the study following an internal safety review, this 
will be done only following approval by Regulatory Authorities. 
11.4. 
Safety Contact Information 
Table 4: 
Ultragenyx Contact Information for SAE Reporting 
Ultragenyx 
Email: Ultragenyx@primevigilance.com 
Fax: +1 415.930.4033 
 

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12. 
STATISTICAL METHODS  
12.1. 
Endpoints and Determination of Sample Size 
A full description of the analysis details will be provided in the statistical analysis plan (SAP). 
12.1.1. 
Primary Endpoint 
The primary endpoint of this study is as follows: 
• The incidence of AEs and SAEs for each cohort and overall assessed by severity and 
relationship to IP 
12.1.2. 
Secondary Endpoint 
The secondary endpoint of this study is as follows: 
• The change from Day 0 (Study 401GSDIA01) in time to first hypoglycemic event 
during a controlled fasting challenge over time by cohort and overall, following IV 
administration of DTX401 
12.1.3. 
Tertiary Endpoints 
The tertiary endpoints of this study are as follows: 
• Total cholesterol, low-density lipoprotein, and triglycerides, by time point, cohort, 
and overall 
• Uric acid, by time point, cohort, and overall  
• 24-hour urine protein, by time point, cohort, and overall 
• The change from baseline in liver size and fat fraction (by MRI) over time following 
IV administration of DTX401, by cohort, and overall 
• The average daily use of cornstarch (or equivalent) over time, by cohort, and overall 
• Assessment of serum glucose levels over time, summarized by cohort 
• Subject responses to HRQoL and sleep quality assessments over time following IV 
administration of DTX401, by cohort and overall 
• Year 2 – Exit Interviews 
• The development of neutralizing antibodies to AAV8 (as determined by a cellbased 
assay) over time, by cohort, and overall 
• The development of anti-AAV8 binding antibodies (as determined by ELISA) over 
time, by cohort, and overall 
• The development of anti-G6Pase antibodies over time, by cohort, and overall 
• Assessment of lactate levels over time, summarized by cohort and overall 

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12.1.4. 
Sample Size Considerations 
The study is expected to enroll approximately up to 12 subjects. This is dependent on the number 
of subjects who enrolled in Study 401GSDIA01 and who meet the eligibility criteria for Study 
401GSDIA02. The sample size is not based on a power calculation. 
12.2. 
Analysis Population 
12.2.1. 
Full Analysis Set 
The full analysis set will consist of all enrolled subjects who received the dose of DTX401. 
Unless specified otherwise, the full analysis set will be used for all the analyses.  
12.3. 
Planned Methods of Analysis 
12.3.1. 
General Principles 
All subjects who provide written informed consent and are enrolled in Study 401GSDIA02 will 
be included in the analyses.  
All statistical evaluations in the study will be descriptive. No formal hypothesis will be tested. 
Continuous variables will be summarized by number of subjects and mean, standard deviation, 
standard error, median, Q1, Q3, minimum, and maximum values. Categorical variables will be 
summarized by number and percentage of subjects. 
An integrated analysis using data from both Study 401GSDIA01 and Study 401GSDIA02 will be 
performed to summarize and assess the long-term safety and efficacy of DTX401; there will not 
be a standalone analysis of data from only Study 401GSDIA02. 
Full details of the analysis will be provided in the SAP. 
12.4. 
Safety Analyses 
12.4.1. 
Adverse Events 
All AEs will be coded according to the Medical Dictionary for Regulatory Activities. The 
incidence of AEs will be summarized for each cohort and overall by system organ class and 
preferred term. Additionally, AEs may be summarized for each cohort and overall by severity 
and relationship to IP, if applicable. Serious AEs will be presented for each cohort and overall by 
relationship to IP. Summary tables will present the total numbers of AEs as well as the number 
of subjects with AE incidence by system organ class and preferred term. For incidence of 
relationship to IP, subjects will be counted only once, in the category of the strongest 
relationship to IP within each system organ class/preferred term. 
12.4.2. 
Hypoglycemic Events 
The number of symptomatic hypoglycemic events occurring during the study reported by the 
subjects will be summarized. Details of the symptomatic hypoglycemic events will be provided 
in a listing. 

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12.4.3. 
MRI Results of the Liver 
Magnetic resonance imaging results will be analyzed for hepatic fat fraction, liver volume, and 
the relative change in each from Study 401GSDIA01 Baseline (Day 0). Descriptive statistics for 
MRI results and changes from baseline values will be summarized by study visit.  
12.4.4. 
Clinical Laboratory Assessments 
For all clinical laboratory parameters with continuous results, absolute values and changes from 
baseline will be summarized by study visit. For laboratory parameters with categorical results, 
shifts from baseline will be summarized by study visit. Laboratory values from the central 
laboratory and local laboratories will be analyzed. 
12.5. 
Efficacy Analyses  
12.5.1. 
Symptom-Free Euglycemia 
Symptom-free euglycemia will be measured using the duration of controlled fasting challenge. 
Duration of controlled fasting challenge is defined as time to any of the following 3 conditions: 
1) glucose <54 mg/dL (<3.0 mmol/L); 2) signs/symptoms of hypoglycemia; or 3) 15 hours 
fasting without hypoglycemia. Change from Baseline will be provided where Day 0 in Study 
401GSDIA01 is considered as baseline.  
12.5.2. 
Use of Cornstarch (or Equivalent) 
Average daily use (both quantity and frequency) of cornstarch over time will be summarized in a 
table and provided in the listings. 
12.5.3. 
Continuous Glucose Monitoring 
Continuous glucose monitoring device data will be summarized. 
12.5.4. 
Morning Glucose Levels 
Glucose levels will be summarized in a table and provided in the listings. 
12.5.5. 
Health-Related Quality of Life and Sleep Quality 
Health-related quality of life and sleep quality over time will be summarized.  
12.6. 
Immunogenicity Analysis 
The development of neutralizing antibodies to AAV8 (as determined by a cell-based assay), 
AAV8 binding antibody IgG (as determined by ELISA), cell-mediated immune response to 
AAV8 and G6Pase, and anti-G6Pase antibodies over time will be summarized. 
12.7. 
Interim Analyses 
Administrative analyses may be performed during the study to support registrational activities, 
respond to regulatory inquiries, or at the Sponsor’s discretion. 

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12.8. 
Data Monitoring Committee 
Not applicable. 

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13. 
STUDY ETHICS AND CONDUCT 
13.1. 
Ethics 
13.1.1. 
Institutional Review Board or Independent Ethics Committee and Competent 
Health Authority 
The IRB/IEC must be a properly constituted board or committee operating in accordance with 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and any 
local ethical and regulatory requirements (eg, 21 CFR Part 56, “Institutional Review Boards,” 
EU Clinical Trials Directive 2001/20/EC, or later guidance). This protocol, any protocol 
amendments, and the associated ICFs must be reviewed and approved by the IRB/IEC and 
Competent Health Authority before screening of any subject.  
IRB/IEC and Competent Health Authority approval of any protocol amendments must be 
received before any of the changes outlined in the amendments are put into effect, except when 
the amendment has been enacted to protect subject safety. In such cases, the chair of the 
IRB/IEC should be notified immediately and the amendment forwarded to the IRB/IEC and 
Competent Health Authority for review and approval. 
13.1.2. 
Ethical Conduct of Study 
This protocol is written in accordance with the principles established by the 18th World Medical 
Assembly General Assembly (the Declaration of Helsinki, 1964) and subsequent amendments 
and clarifications adopted by the General Assemblies. The Sponsor and Investigator will make 
every effort that the study described in this protocol is conducted in full conformance with those 
principles, ICH GCP, and applicable local law, eg, Food and Drug Administration (FDA) 
regulations, European Union (EU) regulations, and any other local ethical and regulatory 
requirements (“Applicable Study Conduct Obligations”) and principles, current Food and Drug 
Administration (FDA) regulations, EU Clinical Trials Directive 2001/20/EC or later, ICH GCP 
guidelines, and local ethical and regulatory requirements. Should a conflict arise, the Sponsor 
and Investigator will follow whichever law or guideline affords the greater protection to the 
individual subject. 
It is the Investigator’s responsibility to inform the Sponsor of any serious breach of the protocol 
(ie, a breach likely to affect to a significant degree the safety and rights of a subject or the 
reliability and robustness of the data generated in the clinical study) within 24 hours of 
identification of the breach. The Sponsor will inform the regulatory authorities of the serious 
breach as required by applicable law or regulation.  
13.1.3. 
Subject Information and Consent 
Appropriate forms for documenting written informed consent will be provided by the 
Investigator and reviewed and approved by Ultragenyx or its designee before submission to the 
IRB/IEC.  
It is the Investigator's responsibility to obtain written informed consent from each potential study 
subject prior to the conduct of any study procedures. This written informed consent will be 
obtained after the methods, objectives, requirements, and potential risks of the study have been 

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fully explained to each potential subject. The Investigator must explain to each subject that the 
subject is completely free to refuse to enter the study or to withdraw from it at any time.  
The method of obtaining and documenting informed consent and the contents of the ICF will 
comply International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines 
and any local ethical and regulatory requirements (eg, 21 CFR Part 56, “Institutional Review 
Boards,” EU Clinical Trials Directive 2001/20/EC, or later guidance). Subjects will be given a 
copy of the signed ICF and will be provided any new information during the course of the study 
that might affect their continued participation in the study. The Investigator or a qualified 
designee will be available to answer each subject's questions throughout the study, and all of the 
subject's questions must be answered to the subject's satisfaction. If the protocol is amended and 
the ICF is revised, each subject will be required to provide written informed consent again using 
the revised ICF. 
The date of written informed consent will be documented in each potential subject’s eCRF. The 
signed ICF will remain in each subject's study file and must be available to the study monitor(s) 
at all times. 
13.1.4. 
Data Protection, Anonymization and Security 
Any study data transferred to Ultragenyx will be coded and will not contain names or any other 
information that would make the subject identifiable. 
Study information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Ultragenyx.  
The subject must be informed of his/her rights under applicable data protection laws regarding 
how his/her personal information is being treated. Additionally, the subject must be informed, 
and where possible, be provided with the details and references, that certain persons or entities 
may have access to his/her medical records for various, legitimate reasons and purposes, 
including Ultragenyx auditors or other authorized personnel appointed by Ultragenyx may 
examine his/her medical records, appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. The subject must also be provided with the applicable contact information 
for Ultragenyx, site, and/or the country’s/regional’s Data Protection Authority in order to inquire 
about their rights, raise concerns, or issue complaints regarding the treatment of his/her personal 
information by Ultragenyx. 
Ultragenyx complies with applicable data protection laws and treats personal information in 
accordance with standard security measures. Ultragenyx has implemented policies and 
procedures to prevent security issues, including data breaches, and avoid/minimize any negative 
consequences. All computerized systems to be used during the study have been selected 
following a strict process that encompassed a System Level Risk Assessment (SLRA), including 
system identification, GxP, General Data Protection Regulation (GDPR), Sarbanes and Oxley 
Act, and 21 CFR Part 11 applicability.  As far GDPR compliance is concerned, a Data 
Classification Assessment which includes the Data Privacy Impact Assessment (DPIA) was also 
conducted on all systems, and their results are memorialized in DPIA assessments stored in the 
Ultragenyx Document Management System. Ultragenyx imposes the same principles to all 
vendors supporting the study, which translates into (i) selecting such vendors and their systems 

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against equally stringent security protocols and standards; (ii) ensuring that they comply with 
applicable data protection laws, and (iii) agreeing to specific data protection terms that include, 
among others, a data breach response plan and an obligation to collaborate with Ultragenyx in 
such circumstances timely. These measures exist so Ultragenyx can mitigate any security 
occurrence and meet their obligations under applicable data protection laws. Therefore, in case 
of a data breach, Article 33 GDPR will be followed. Additionally, in order to maintain/restore a 
GxP-compliant environment, an audit will be conducted, and the necessary remedial actions 
implemented in a timely fashion (including, but not limited to, termination of any relevant third 
party from the research) to guarantee the integrity of the concerned data and avoid any future 
repetition. 
13.1.5. 
Future Use of Stored Study Samples 
Not applicable.  
13.2. 
Investigators and Study Administrative Structure 
Each Investigator must provide Ultragenyx and/or its designee a completed and signed Form 
FDA 1572, or equivalent, if applicable based on local requirements, and a Financial Disclosure 
Form. All subinvestigators must be listed on Form FDA 1572, or equivalent, and Financial 
Disclosure Forms must be completed for all subinvestigators listed on Form FDA 1572. 
13.2.1. 
Investigator Documentation 
Prior to beginning the study, the Investigator will be asked to comply with ICH E6 (R2) 8.2 and 
Title 21 of the CFR by providing the following essential documents, including but not limited to: 
• IRB/IEC/IBC approvals 
• Original Investigator-signed Investigator agreement page of the protocol 
• Form FDA 1572 (or equivalent), fully executed, and all updates on a new fully 
executed Form FDA 1572 (or equivalent) 
• Curriculum vitae for the Investigator and each subinvestigator 
• Financial disclosure information to allow the sponsor to submit complete and 
accurate certification or disclosure statements required under 21 CFR §54. In 
addition, the Investigators must provide to the sponsor a commitment to promptly 
update this information if any relevant changes occur during the course of the 
investigation and for 1 year after the completion of the study 
• IRB/IEC/IBC-approved ICF, samples of study site advertisements for recruitment for 
this study, and any other written information regarding this study that is to be 
provided to the subject or their legal guardian 
• Laboratory certifications and normal ranges for any local laboratories used by the 
study site, in accordance with 42 CFR §493 
13.3. 
Investigational Product Accountability 
Not applicable. 

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13.4. 
Data Handling and Record Keeping 
13.4.1. 
Case Report Forms and Source Documents 
The Investigator is required to initiate and maintain, for each subject, an adequate and accurate 
case history that records all observations and other data related to the study for that subject. A 
validated EDC system will be used for entry of the data into eCRFs. Data must be recorded on 
eCRFs approved by Ultragenyx or its designee. All information recorded on eCRFs for this study 
must be consistent with the subject's source documentation.  
Initial data entry and any changes to the data will be made only by Ultragenyx-authorized users, 
and data entries and changes will be captured in an electronic audit trail. An explanation of any 
data change should be recorded in the eCRF. All data entered in to the eCRF must be verifiable; 
therefore, eCRFs will be routinely checked for accuracy, completeness, and clarity and will be 
cross-checked for consistency with source documents, including laboratory test reports and other 
subject records by Ultragenyx or its designee. The Investigator must allow Ultragenyx or its 
designee direct access to all source documents. 
13.4.2. 
Data Quality Assurance 
Monitoring and auditing procedures developed by Ultragenyx and/or its designee will be 
implemented to ensure compliance with FDA and ICH GCP guidelines. The Ultragenyx 
designated representative (the monitor) will contact the Investigator and conduct regular visits to 
the study site, according to the monitoring plan. The monitor will also be responsible for 
confirming adherence to the study protocol, inspecting eCRFs and source documents, and 
ensuring the integrity of the data. Instances of missing or uninterpretable data will be resolved in 
coordination with the Investigator. 
The monitor will also investigate any questions concerning adherence to regulatory 
requirements. Any administrative concerns will be clarified and followed. The monitor will 
maintain contact with the site through direct communications with the study site by e-mail, 
telephone, facsimile, and/or mail. The Investigator and all other site personnel must agree to 
cooperate fully with the monitor and will work in good faith with the monitor to resolve any and 
all questions raised and any and all issues identified by the monitor. 
The Investigator should understand that regulatory authorities, the IRB/EC, and/or Ultragenyx or 
its designees have the right to access all eCRFs, source documents, and other study 
documentation for on-site audit or inspection and will retain this right from the start of the study 
to at least 2 years after the last approval of a marketing application or for at least 2 years after 
clinical development of the IP for the indication being studied has been discontinued. The 
Investigator is required to guarantee access to these documents and to cooperate with and support 
such audits and inspections. 
13.4.3. 
Record Retention 
All study records must be retained in strict accordance with the Clinical Trial Agreement 
executed between Ultragenyx and the Institution and/or Investigator. For study monitoring, audit, 
or inspection, the IRB/IEC and Sponsor or its designees have the right to access all CRFs, source 
documents, and other study documentation. The Investigator or study site will retain such 

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documents from the start of the study to at least 25 years after the close of the study, guarantee 
access to these documents, and cooperate with and support such audits and inspections. 
13.5. 
Financing and Insurance 
Financing and insurance for this clinical study will be addressed in the Clinical Trial Agreement 
between Ultragenyx and the Institution and/or Investigator. 
13.6. 
Publication Policy 
Any publication or presentation by the Investigator and/or the Institution associated with the 
study will be in strict accordance with the Clinical Trial Agreement executed between 
Ultragenyx and the Institution and/or Investigator. 

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14. 
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Van Alstyne M, Tattoli I, Delestree N, et al. (2021) Gain of toxic function by long-term AAV9-
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APPENDICES

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APPENDIX 1. PROMIS-29 
 

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APPENDIX 2. PROMIS SOCIAL ISOLATION – SHORT FORM 4A 

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APPENDIX 3. PITTSBURGH SLEEP QUALITY INDEX (PSQI) 

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APPENDIX 4. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) 

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APPENDIX 5. PATIENT GLOBAL IMPRESSION OF CHANGE (PGI-C)