Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease

Study Overview
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Brief Summary
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This study aimed to determine the efficacy and safety of lucerastat oral monotherapy in adult subjects with Fabry disease.

Detailed Description
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The primary objective of this prospective, multicenter, double-blind, randomized, placebo-controlled, parallel group, Phase 3 study is to determine the effect of oral lucerastat monotherapy on neuropathic pain in subjects with Fabry disease (FD) through daily collection of patient-reported outcomes with an electronic diary.

Official Title
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A Multicenter, dOuble-blind, ranDomized, Placebo-controlled, Parallel-group Study to Determine the effIcacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With FabrY Disease

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: Lucerastat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated ICF prior to any study-mandated procedure; Male or female adult subjects; FD diagnosis confirmed with local genetic test results; Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening; Enzyme replacement therapy (ERT) status: Subject never treated with ERT; or Subject has not received ERT for at least 6 months prior to screening; or Subject treated with ERT since at least 12 months at the time of the screening visit, and agreeing to stop ERT for approximately 8 months. A woman of childbearing potential is eligible only under certain conditions, e.g. taking contraceptive measures. Subjects with moderate or severe neuropathic pain during the screening period. Exclusion Criteria: Pregnant, planning to be become pregnant, or lactating subject. Severe renal insufficiency (eGFR < 30 mL/min/1.73 m2) at screening. Subject on regular dialysis for the treatment of chronic kidney disease. Known and documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within 6 months prior to screening. Clinically significant unstable cardiac disease (e.g. uncontrolled symptomatic arrhythmia, congestive heart failure NYHA class III or IV). Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lucerastat<br> | Drug: Lucerastat<br>* Hard gelatin capsules containing 250 mg of lucerastat and inactive excipients; 1000 mg (4 capsules) twice daily (b.i.d.); dose adjusted for renal function.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo capsules are identical in appearance to the lucerastat capsules, and contain inactive excipients; 4 capsules b.i.d.; dose adjusted for renal function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Month 6 in the modified Brief Pain Inventory-Short Form 3 (BPI-SF3) score of neuropathic pain at its worst in the last 24 hours |  | From baseline to Month 6 (duration: 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Month 6 in the 11-point Numerical Rating Scale (NRS-11) score of abdominal pain at its worst in the last 24 hours in subjects with GI symptoms at baseline. |  | From baseline to Month 6 (duration: 6 months) | 
| Change from baseline to Month 6 in the number of days with at least one stool of a Bristol Stool Scale (BSS) consistency Type 6 or 7 in subjects with GI symptoms at baseline. |  | From baseline to Month 6 (duration: 6 months) | 
| Change from baseline to Month 6 in plasma globotriaosylceramide (Gb3). |  | From baseline to Month 6 (duration: 6 months) |