Evaluation of Long-Term Safety and Pregnancy Outcomes of Pariglasgene Brecaparvovec in Patients with Glycogen Storage Disease Type Ia (GSDIa)

The primary objective of this study is to evaluate the long-term **safety** and pregnancy outcomes of DTX401 in patients with **Glycogen storage disease type Ia (GSDIa)**. This is clinically relevant as it aims to ensure that the treatment does not pose significant risks to patients over an extended period, particularly concerning reproductive health, which is crucial for patient quality of life and informed decision-making regarding treatment options.

Secondary objectives include evaluating the long-term effectiveness of DTX401 in patients with GSDIa. This assessment is important to determine the sustained therapeutic benefits of the treatment, thereby providing insights into its potential as a viable long-term management option for GSDIa.

The clinical trial involves a total of **134 participants** diagnosed with **Glycogen storage disease type Ia (GSDIa)**. The study population includes both male and female subjects, encompassing a broad age range from children to adults. Participants were selected based on their previous administration of DTX401, either in a parent clinical study or a post-marketing setting. The trial includes a vulnerable population, indicating that special considerations are in place for minors or adults with cognitive limitations. Participants are required to provide informed consent, with assent and consent from a legally authorized representative if necessary. The study aims to evaluate the long-term safety and pregnancy outcomes of DTX401 in this specific patient group. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the long-term safety and pregnancy outcomes of **DTX401** in patients with **glycogen storage disease type Ia (GSDIa)**. This study is a low-intervention, disease monitoring program that follows a phase III and phase IV integrated approach. The trial will involve patients who have previously received **DTX401** either in a parent clinical study or in a post-marketing setting. The trial is expected to span over a period of at least 10 years, with an estimated recruitment start date in October 2024 and an estimated end date in December 2036.

The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on the inclusion criteria, which include prior administration of **DTX401** and the ability to provide informed consent. Follow-up visits will be scheduled periodically to monitor the incidence and severity of serious adverse events (SAEs) and adverse events of special interest (AESIs) related to **AAV therapies**. These visits will also assess the incidence and outcomes of pregnancy in patients treated with **DTX401** or their partners.

The end-of-study visit will mark the conclusion of the participant's involvement in the trial, where final assessments will be conducted to evaluate the long-term safety and effectiveness of the treatment. The expected length of participant involvement is contingent upon the trial's duration, with the possibility of early termination if significant safety concerns arise or if the participant withdraws consent. The primary endpoints include the incidence and severity of SAEs related to **DTX401**, while secondary endpoints focus on nutritional assessments, clinical evaluations, and patient experience interviews. The trial aims to provide comprehensive data on the long-term impact of **DTX401** in managing **GSDIa**.

The clinical trial involves the administration of **Pariglasgene brecaparvovec**, an experimental medication designed for the treatment of Glycogen Storage Disease Type Ia (GSDIa). This investigational product is provided in the form of a **solution for infusion**. The active substance, **pariglasgene brecaparvovec**, is a structurally diverse substance, specifically an adeno-associated viral vector serotype 8 containing the human glucose-6-phosphatase gene. The pharmaceutical form is a solution intended for intravenous administration. The dosing regimen is characterized by a single administration, with no specified maximum daily or total dose amount, and the treatment period is limited to one day. The product is not formulated for pediatric use and is designated as an orphan drug under the designation number EU/3/16/1771.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the long-term safety and pregnancy outcomes of the investigational product, DTX401, in patients with GSDIa. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial is conducted under the sponsorship of Ultragenyx Pharmaceutical Inc., and the investigational product is identified by the sponsor product codes DTX401 and AAV8G6PC.

The clinical trial aims to assess the efficacy of **Pariglasgene brecaparvovec** in patients with Glycogen Storage Disease Type Ia (GSDIa) through a Disease Monitoring Program. The primary endpoints for evaluating efficacy include the incidence and severity of serious adverse events (SAEs) related to DTX401, as assessed by the investigator. Additionally, the trial will monitor the incidence, relationship, severity, and seriousness of adverse events of special interest (AESIs) associated with AAV therapies, such as vector-induced hepatic effects, malignancy, thrombotic microangiopathy, dorsal root ganglion/peripheral nerve effects, and any new potential risks identified over time. The trial will also evaluate the incidence and outcomes of pregnancy in patients treated with DTX401 or their partners, as well as the incidence and severity of infusion-related reactions, including hypersensitivity, and SAEs related to concomitant immunomodulatory therapies.

Secondary endpoints include a comprehensive nutritional assessment, clinical and laboratory evaluations, major clinical events (MCEs), patient experience clinical interviews, and health economics and outcomes research (HEOR). The trial is designed to follow patients for at least 10 years after DTX401 administration, focusing on long-term safety and effectiveness. Data collection will involve clinical, laboratory, and imaging assessments, as well as patient-reported outcomes. The trial is categorized as a low-intervention study, integrating phase III and phase IV elements, and aims to provide a thorough evaluation of the long-term impact of DTX401 on patients with GSDIa.