A Study to Learn How Well Lucerastat Works and How Safe it is in Untreated Adult Male Participants With Fabry Disease

A Multicenter, Open-label, Single-arm, Baseline-controlled Trial to Assess the Efficacy and Safety of Lucerastat in Treatment-naïve/Pseudo-naïve Adult Male Participants With Fabry Disease

The purpose of this clinical trial is to learn how well lucerastat works and how safe it is in untreated adult male participants with Fabry disease.

The main question this clinical trial aims to answer is:

• Does treatment with lucerastat affects the amount of globotriaosylceramide (Gb3), a fatty substance that builds up in the kidneys, in untreated adult men with Fabry disease?

This is an open-label, single-arm trial, which means that participants will know which trial medication they receive and only one trial medication will be given.

Trial participants will:

• Take lucerastat every day for 18 months
• Have kidney biopsies at the end and start of the trial
• Visit the clinic 10 times for check-up and tests
• Take part in the trial for up to 21 months in total

Inclusion Criteria:

• Confirmed diagnosis of Fabry disease:

  • Plasma and/or leukocyte α-galactosidase A (α-GalA) < 1% mean normal levels or
  • Known "pathogenic" or "likely pathogenic" Gene coding for α-galactosidase A (GLA) variant with a low level (i.e., < 30% mean normal levels) of plasma and/or leukocyte α-GalA.

• History of at least one of the following clinical manifestations of Fabry disease:

  • Neuropathic pain
  • Cornea verticillata
  • Angiokeratoma

• Treatment-naïve or pseudo-naïve i.e. without prior treatment with an approved or any investigational therapy for Fabry disease within at least 6 months prior to screening.

• Plasma globotriaosylsphingosine ≥ 20 ng/ml (as assessed centrally).

• Screening eGFR (central laboratory) ≥ 45 mL/min/1.73 m2.

Exclusion Criteria:

• Any intercurrent condition or concomitant therapy considered a contraindication for kidney biopsy, as per local standard of care, or in the investigator's opinion may preclude accurate interpretation of trial data.
• Urine albumin-to-creatinine ratio > 300 mg/g at screening (central laboratory) unless treated with background therapy, such as Angiotensin-converting enzyme inhibitors, Angiotensin receptor blocker or Sodium-glucose cotransporter 2 inhibitors, as per local practice.
• Inherited or acquired coagulopathy, uncorrected bleeding disorders, international normalized ratio > 1.5, platelet count < 50,000/μL or inability to safely hold anticoagulants or antiplatelet therapy as applicable per local practice (usually 1-2 days for anticoagulants and 3-7 days for antiplatelets).
• Hemoglobin level < 9.0 g/dL at screening.
• History of acute kidney injury within 12 months prior to screening visit.
• Documented poorly controlled diabetes mellitus (i.e., Hemoglobin A1c > 8.0% at screening as reported by the central laboratory).
• History of cerebrovascular event (e.g. stroke, transient ischemic attack), cardiovascular event (e.g., myocardial infarction, unstable angina), cardiac surgery (e.g., coronary artery bypass graft, valvular repair/replacement) or percutaneous coronary intervention within 6 months prior to screening.
• Congestive heart failure New York Heart Association class IV or hospitalization for heart failure within 3 months prior to screening.
• Implementation of cardiac device (e.g., pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device) or hospitalization for arrhythmia within 6 weeks prior to screening.
• Any other known factor or disease that might interfere with treatment compliance, trial conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease including severe depression or suicidal ideation at screening or history of suicide attempt or behavior within 6 months prior to screening visit.
• Previous exposure to gene or cell therapy.
• Use of cationic amphiphilic drugs, such as amiodarone or hydroxychloroquine that may preclude accurate interpretation of kidney biopsy data within 6 months prior to screening.