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 401GSDIA02 is 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). 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. No investigational product will be
administered during Study 401GSDIA02.

GSDIa is an inherited disorder caused by a deficiency in the gene (referred to
as G6PC) for glucose-6-phosphatase (G6Pase). Because of this deficiency, people
with GSDIa are not able to maintain safe and healthy levels of blood sugar
(glucose).

People with GSDIa develop low blood sugar (hypoglycemia) within a few hours
after eating unless they manage their blood sugar with cornstarch or other
dietary therapy. If low blood sugar levels are not treated properly, serious
side effects, such as seizures or even death, can occur. GSDIa can also prevent
some of the body*s organs and tissues from working normally.

The DTX401 vector is called adeno-associated virus (AAV); it is used to deliver
the G6PC gene to your liver. AAV is a common virus found throughout the body in
natural infections. It is not currently known to cause disease.

This study has been transitioned to CTIS with ID 2023-504004-29-00 check the CTIS register for the current data.

To determine the long-term safety of DTX401 following a single IV dose in
adults with GSDIa

In Study 401GSDIA02, subjects will be followed for approximately 4 years, for a
total of 5 years of follow-up after administration of DTX401 in 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 260 (Year 5) for safety and efficacy
evaluations. Subjects who are waiting to enroll in the DTX401 disease
monitoring program [DMP] at the end of Year 5 may continue for up to 1
additional year in the study, thus having a follow-up until Week 312 (i.e.
total follow-up of approximately 6 years after the administration of DTX401).
Once the DMP is available to enroll, subjects can enter the DMP after the Study
401GSDIA02 Week 208 visit has been completed. The DMP is a long-term follow-up
study to evaluate safety and effectiveness of DTX401 for at least 10 years
after DTX401 administration. The DMP for GSDIa will be conducted under a
separate protocol.

Please refer for an overview of study procedures to table 1, in the protocol.

Subjects mainly have to follow the following study procedures:
* medical history and physical exam
* carrying continuous glucose monitoring device (CGM)
* completing questionnaires
* urine and blood sampling
During the inpatient days also:
* ECG, ultrasound liver, MRI liver
* controlled fasting challenge
* 24h urine sample collection
* 30 min telephone interview

During this study, there are no IP associated risks, since no IP will be
provided. Potential risks for the patient are associated with the various study
procedures, such as ECG (e.g. skin irritation), blood sampling (e.g. potential
painful site needle puncture), controlled fasting challenge (e.g. sweating,
confusion) etc.

Below you can find the explained risks for subjects:
Potential Risks Associated with Study Procedures
You will be asked to give several blood samples during the study. Over the
course of the study, you will give about 1250 mL of blood in total.

You may experience pain, a pinching feeling, or bruising at the site where the
needle is inserted. There is a small risk of infection at the needle puncture
site. Some people experience dizziness, upset stomach, or fainting when their
blood is drawn. Blood will be drawn by a qualified person who will ensure that
all safety measures are followed to reduce the risks. The intended use of the
blood samples is to assess and monitor your safety to participate in the study.
If an important change is observed, the study doctor will review the results
and will provide proper care.

You will be asked to undergo an ultrasound of your liver during specific study
visits. There are no significant risks due to ultrasound. You may feel
uncomfortable when the gel is applied and while the technician is pressing the
hand-held device on your body to locate your liver.

You will be asked to undergo MRI scans periodically during the study. There are
no significant risks due to MRI scans. You may be bothered by the sounds made
by the MRI machine and by feelings of being closed in (claustrophobia). In some
rare cases, nausea and dizziness have been reported. There is a risk of
distress due to the closed space of the scanner. However, you will be provided
with a panic button which, when pressed, will alert the technician to stop the
test. Because the MRI involves use of a large magnet, there may be risks if you
have metal in your body that you have not disclosed to the study staff. Before
the MRI scan is performed, be sure to tell the study staff if you have any of
the following:
• Pacemaker
• Heart or vascular clip (including an aneurysm clip)
• Prosthetic heart valve
• Metal prosthesis (for example, an artificial hip or knee joint)
• Pregnancy
• Distress due to closed space
• Metal fragments in body
• Transdermal patches (Patches must be removed before the MRI scan. You may
bring another patch to reapply after your scan.)
• Color contact lens
• Body piercing
• Permanent make up or tattoo

Potential Risks Associated with COVID-19
Depending on the current status of the COVID-19 pandemic, the study doctor may
make adjustments to your visit schedule or change the type of visit you have.
If your visit is changed to a remote visit, the visit-specific assessments may
be collected by a home health nurse to protect your health and well-being.