Evaluation of Venglustat on Neuropathic and Abdominal Pain in Treatment-Naïve or Untreated Fabry Disease Patients Aged ≥16 Years: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective is to evaluate the efficacy of venglustat in reducing neuropathic pain or abdominal pain in participants aged 16 years or older with Fabry disease who are treatment-naïve or have remained untreated for at least 6 months. Secondary objectives include:

• Assessment of plasma globotriaosylsphingosine (lyso-GL-3) levels
• Evaluation of the requirement for rescue pain medication
• Monitoring of Fabry disease symptoms
• Evaluation of safety and tolerability
• Assessment of pharmacokinetics

This study involves 76 participants diagnosed with Fabry disease. The study population consists of male and female patients aged 16 years or older. Eligible individuals are either treatment-naïve or have remained untreated by any approved or experimental therapy for at least 6 months prior to screening. Participants must have a body weight of at least 30 kg. A primary requirement is a reported average score of 3 or higher on the Fabry Disease Patient-Reported Outcome for their most bothersome symptom, which includes neuropathic pain in the upper or lower extremities or abdominal pain. Specific requirements regarding contraception and the avoidance of pregnancy or breastfeeding are also established for this cohort.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy of venglustat on neuropathic pain and abdominal pain in participants with Fabry disease. The study involves participants aged 16 years or older who are either treatment-naïve or have been untreated for at least 6 months. Following a screening visit to confirm diagnosis and eligibility, participants are assigned to receive either venglustat or a placebo via oral administration. The total duration of participant involvement is estimated at 12 months. The clinical assessment includes evaluating the percent change from baseline in the most bothersome symptoms as measured by the Fabry Disease Patient-Reported Outcome. Secondary endpoints consist of measurements including plasma globotriaosylsphingosine levels, frequency of rescue medication use, and ophthalmological examinations. The trial period concludes with an end-of-study visit to complete the final assessments.

The experimental treatment consists of venglustat, an orphan drug. It is administered in tablet form via oral use at dosages of either 12 mg or 15 mg.

The control arm utilizes a placebo. This is administered in tablet form at dosages of either 6 mg or 15 mg.

The primary efficacy assessment involves the percent change from baseline at 6 and 12 months in the most bothersome symptom among three Fabry Disease Patient-Reported Outcome (FD-PRO) items, which include neuropathic pain in the upper extremities, neuropathic pain in the lower extremities, or abdominal pain.

Secondary endpoints include:

• Percent change in plasma globotriaosylsphingosine (lyso-GL-3) levels.
• Frequency of rescue pain medication use.
• Change in the percentage of days with at least one stool reflecting diarrhea, as measured by the Bristol Stool Form Scale (BSFS).
• Change in the tiredness component of the FD-PRO.
• Proportion of responders in neuropathic or abdominal pain as assessed by FD-PRO.
• Change in lens clarity via ophthalmological examination using a slit lamp exam at Visit 2 and Visit 6.
• Change in the Beck Depression Inventory-II (BDI-II) score.
• Pharmacokinetic parameters, including plasma venglustat concentrations, maximum plasma concentration (Cmax), time to maximum concentration (tmax), and area under the curve (AUC0-24).