Long-Term Safety Evaluation of Isaralgagene Civaparvovec Gene Therapy in Patients with Fabry Disease

The primary objective of this study is to evaluate the long-term **safety** of **ST-920**, a gene therapy product, in subjects with **Fabry Disease**. Fabry Disease is an X-linked lysosomal storage disorder characterized by the buildup of globotriaosylceramide due to deficient activity of the enzyme alpha-galactosidase A. The clinical relevance of this objective lies in ensuring the sustained safety of ST-920, which utilizes an adeno-associated virus serotype 2/6 vector encoding the cDNA for human alpha-galactosidase A, as a therapeutic intervention for this condition. The study does not specify any secondary objectives.

The clinical trial involves a total of **44 male participants** who are being evaluated for the long-term safety of ST-920 in the context of **Fabry Disease**, an X-linked lysosomal storage disease. The study population consists of adult males, as indicated by the age range categories 3 and 4, which correspond to ages 18-64. Participants were selected based on their prior involvement in a separate parent trial where they received ST-920 therapy, and all have consented to participate in this long-term follow-up study. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The sponsor has not provided additional information regarding the general health status or other lifestyle habits of the participants.

The clinical trial is designed to evaluate the long-term safety of **ST-920**, a gene therapy for **Fabry Disease**, an X-linked lysosomal storage disorder. This trial is a Phase 4, long-term follow-up study involving subjects who have previously received **ST-920** therapy in a separate parent trial. The study is structured as a non-randomized, open-label trial, focusing on the assessment of the incidence and severity of adverse events as the primary endpoint. The trial is expected to commence recruitment on March 1, 2025, and is estimated to conclude by March 1, 2040, providing a comprehensive evaluation over a 15-year period.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on prior participation in the parent trial and consent to partake in this follow-up study. Subsequent follow-up visits will be scheduled periodically to monitor the long-term safety profile of the therapy, with assessments focusing on the occurrence and severity of any adverse events. The end-of-study visit will mark the conclusion of the participant's involvement, summarizing the safety data collected throughout the trial duration.

The expected length of participant involvement spans the entire duration of the trial, approximately 15 years, unless conditions necessitate early termination. Such conditions may include withdrawal of consent, significant protocol deviations, or the emergence of safety concerns that warrant discontinuation of participation. The trial is categorized as a Category 2 study, indicating its focus on long-term safety follow-up, and does not involve a pediatric formulation. The investigational product, **ST-920**, is administered as a solution for injection/infusion, with no specified maximum daily or total dose, reflecting its role as a gene therapy product rather than a conventional pharmacological treatment.

The clinical trial involves the administration of **ST-920**, a gene therapy product developed by Sangamo Therapeutics, Inc. The active substance in ST-920 is **isaralgagene civaparvovec**, a recombinant adeno-associated virus 2/6 vector encoding the cDNA for human alpha-galactosidase A. This investigational product is formulated as a **solution for injection/infusion**. The administration route is categorized as "other use," indicating a specialized method of delivery that is not specified in standard categories. The dosing regimen does not specify a maximum daily or total dose, and the treatment period is limited to a single administration. The product is not formulated for pediatric use and has been designated as an orphan drug under the designation number EU/3/19/2241.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the long-term safety evaluation of ST-920 in subjects with Fabry disease. Participant compliance with the treatment protocol is monitored through standard clinical trial procedures, ensuring adherence to the administration schedule and accurate reporting of any adverse events or deviations from the protocol.

Efficacy in the clinical trial will be assessed through the evaluation of long-term safety of **ST-920**, a gene therapy for Fabry Disease. The primary endpoint involves the assessment of the incidence and severity of adverse events (AEs) associated with the treatment. This will be conducted as part of a long-term follow-up study, focusing on subjects who have previously received **ST-920** therapy in a separate parent trial. The trial is designed to monitor these parameters over an extended period, with the estimated end date set for March 1, 2040. The trial is categorized as a Phase 4 study, indicating its focus on post-marketing surveillance to ensure ongoing safety and efficacy of the treatment. The data collection and analysis will be conducted in accordance with standard clinical trial protocols, ensuring rigorous and systematic evaluation of the safety profile of the therapy.