Long-term Safety and Tolerability Assessment of Oral Lucerastat in Adult Patients with Fabry Disease: An Open-label, Uncontrolled, Single-arm Extension Study

The primary objective of this study is to determine the long-term **safety** and **tolerability** of oral lucerastat in adult subjects with **Fabry disease**. This is clinically relevant as it aims to assess the potential of lucerastat as a sustainable treatment option, ensuring that it can be safely administered over an extended period without adverse effects, which is crucial for chronic conditions like Fabry disease.

Secondary objectives include:

• Evaluating the effect of lucerastat on **renal function** and **cardiac variables** in subjects with Fabry disease. This is important for understanding the broader impact of the treatment on organ systems commonly affected by the disease.
• Assessing the long-term effect of lucerastat on **biomarkers** of Fabry disease, which could provide insights into the disease-modifying potential of the treatment and its impact on disease progression.

The clinical trial involves a total of **58 participants** diagnosed with **Fabry disease**. The study population includes both male and female subjects, with an age range that spans from 18 to 64 years. Participants were selected based on their completion of a prior 6-month, double-blind treatment period in study ID 069A301. The trial does not include any vulnerable populations. The general health status of the participants is not specified, nor are there any particular lifestyle considerations such as diet or physical activity mentioned. The selection criteria required participants to have signed and dated an informed consent form prior to any study-mandated procedures.

The clinical trial is designed as a **multi-center, open-label, uncontrolled, single-arm, extension study** to evaluate the long-term safety and tolerability of oral **lucerastat** in adult subjects diagnosed with **Fabry disease**. The trial aims to assess treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as primary endpoints. The study is expected to span from December 7, 2018, to November 23, 2027, with a maximum treatment period of 72 months. Participants will be administered lucerastat in the form of hard capsules, with a maximum daily dose of 2000 mg, taken orally.

Participants eligible for inclusion must have completed a prior 6-month, double-blind treatment period in study ID 069A301 and must provide a signed and dated informed consent form (ICF) before any study-mandated procedures. The study does not specify any principal exclusion criteria. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and tolerability, and an end-of-study visit to conclude participation. The expected length of participant involvement is up to 72 months, contingent upon the absence of any conditions that may necessitate early termination, such as significant adverse events or withdrawal of consent.

The clinical trial involves the administration of **Lucerastat**, an experimental medication developed by Idorsia Pharmaceuticals Ltd. Lucerastat is provided in the form of a hard capsule, intended for **oral use**. The active substance in Lucerastat is chemically derived and is also known by the synonyms ACT-434964 and N-Butyldeoxygalactonojirimycin. The maximum daily dose of Lucerastat is 2000 mg, with the same amount being the maximum total dose permissible within a 24-hour period. The treatment period for participants is set at a maximum of 72 weeks. The primary objective of the trial is to assess the long-term safety and tolerability of Lucerastat in adult subjects diagnosed with **Fabry disease**.

In this study, Lucerastat is the sole investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized. The trial is designed as a multi-center, open-label, uncontrolled, single-arm extension study. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial does not include a pediatric formulation of Lucerastat, and the medication is classified as an orphan drug, designated under the number EU/3/12/1033.

The efficacy of the clinical trial involving **Fabry disease** will be assessed primarily through the evaluation of treatment-emergent adverse events (AEs) and serious adverse events (SAEs). These parameters will serve as the primary endpoints to determine the long-term safety and tolerability of the investigational product, lucerastat, administered orally in the form of hard capsules. The trial is designed as a multi-center, open-label, uncontrolled, single-arm extension study. The assessment of efficacy will be conducted over a maximum treatment period of 72 weeks. Data collection will focus on the incidence and severity of AEs and SAEs, which will be systematically recorded and analyzed throughout the study duration. The trial aims to provide comprehensive safety data to support the therapeutic use of lucerastat in adult subjects with Fabry disease.