|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Fabry disease is a rare, inherited disease caused by a genetic defect which leads to an accumulation of fatty substance in the body. Symptoms include stomach pain and damage to vital organs.
|Diseases [C] - Nutritional and Metabolic Diseases [C18]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|• To determine the effect of lucerastat on neuropathic pain in subjects with Fabry disease (FD).
|Secondary objectives of the trial
|• To determine the effects of lucerastat on gastro-intestinal (GI) symptoms (abdominal pain and diarrhea) in subjects with FD and GI symptom(s) at baseline.
• To confirm the effect of lucerastat on biomarkers of FD.
• To determine the safety and tolerability of lucerastat in subjects with FD.
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|PK profile sub-study (all sites): A sub-study will be conducted at all sites to determine the PK profile of lucerastat at steady state in a subgroup of approximately 36 subjects with FD with either normal or subnormal renal function (i.e., screening eGFR ≥ 60 mL/min/1.73 m2) or impaired renal function (i.e., screening eGFR < 60 mL/min/1.73 m2). If necessary, blood samples collected for PK may be used for the identification of potential metabolites of lucerastat in this population. Subjects consenting to this sub study will have a 12-hour PK profile performed at the Month 1 visit.
|Principal inclusion criteria
|1. Signed and dated ICF prior to any study-mandated procedure.
2. Male or female subjects; 18-years old and above.
3. FD diagnosis confirmed with local genetic test results (i.e., presence
of at least 1 mutation in GLA, the gene coding for α-
4. Fabry-associated neuropathic pain, as defined by the subject, in the
last 3 months prior to screening.
|Principal exclusion criteria
|1. Pregnant, planning to be become pregnant up to 30 days after study
treatment discontinuation or lactating subject;
2. Severe renal insufficiency defined as an estimated glomerular
filtration rate (eGFR) per the Chronic Kidney Disease Epidemiology
Collaboration creatinine equation < 30 mL/min/1.73 m2 at screening;
3. Subject on regular dialysis for the treatment of chronic kidney
4. Subject has undergone, or is on a waiting list for, or is scheduled to
undergo kidney or other organ transplantation;
5. Known and documented transient ischemic attack, stroke, unstable
angina or myocardial infarction within 6 months prior to screening;
6. Clinically significant unstable cardiac disease in the opinion of the
investigator (e.g., uncontrolled symptomatic arrhythmia, New York
Heart Association class III or IV congestive heart failure);
7. Any other subject at high risk for developing clinical signs of organ
involvement within the time period of the study, as per investigator
8. Subject planned for imminent initiation of treatment with ERT.
|E.5 End points
|Primary end point(s)
|The primary efficacy endpoint is change from baseline to Month 6 in the "modified" Brief Pain Inventory-Short Form item 3 (BPI-SF3) score of "neuropathic pain at its worst in the last 24 hours".
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• 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.
• 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.
• Change from baseline to Month 6 in plasma globotriaosylceramide (Gb3).
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
If the last subject enters the OLE study, the end of the trial corresponds to the EOT visit. If the last subject does not enter the OLE study, the end of the trial corresponds to the FU1 visit, FU2 visit, or to the last visit of the PTOP, whichever is last.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days