E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease |
Enfermedad de Fabry |
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E.1.1.1 | 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. |
La enfermedad de Fabry es una enfermedad rara y hereditaria causada por un defecto genético que causa acumulación de sustancias grasas. Los síntomas incluyen dolor de estómago y daño a órganos vitales |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016016 |
E.1.2 | Term | Fabry's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To determine the effect of lucerastat on neuropathic pain in subjects with Fabry disease (FD). |
• El objetivo principal del estudio es determinar el efecto de lucerastat sobre el dolor neuropático en sujetos con enfermedad de Fabry (EF). |
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E.2.2 | 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. |
• Determinar los efectos de lucerastat sobre los síntomas digestivos (dolor abdominal y diarrea) en sujetos con EF y síntomas digestivos en el momento basal. • Confirmar el efecto de lucerastat sobre los biomarcadores de la EF. • Determinar la seguridad y la tolerabilidad de lucerastat en sujetos con EF. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | 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. |
Sub-estudio de perfil de farmacocinética (en todos los centros): se realizará un subestudio en todos los centros para determinar el perfil de FC de lucerastat en estado estacionario en un subgrupo de aproximadamente 36 sujetos con EF con función renal normal o infranormal (es decir, detección de TFGe ≥ 60 ml / min / 1,73 m2) o insuficiencia renal (es decir, detección de TFGe <60 ml / min / 1,73 m2). Si es necesario, las muestras de sangre recogidas para farmacocinética pueden usarse para la identificación de metabolitos potenciales de lucerastat en esta población. Los sujetos que den su consentimiento para este subestudio tendrán un perfil de farmacocinética de 12 horas realizado en la visita del mes 1. |
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E.3 | 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 alfa- galactosidase A). 4. Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening. |
1. DCI firmado y fechado antes de cualquier procedimiento exigido por el estudio. 2. Varones o mujeres mayores de 18 años. 3. Diagnóstico de EF confirmado con los resultados del análisis genético del centro (es decir, presencia de al menos una mutación en GLA, el gen que codifica la alfagalactosidasa A. 4. Dolor neuropático asociado a la enfermedad de Fabry, definido por el sujeto, en los 3 meses previos a la selección. |
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E.4 | 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 disease; 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 judgment; 8. Subject planned for imminent initiation of treatment with ERT. |
1. Mujer embarazada o que planea quedarse embarazada hasta 30 días después de la terminación del tratamiento del estudio, o mujer en período de lactancia. 2. Insuficiencia renal grave, definida como una filtración glomerular estimada (FGe) < 30 ml/min/1,73 m 2 según la ecuación de creatinina Chronic Kidney Disease Epidemiology Collaboration en la selección 3. Sujeto que recibe diálisis regularmente para el tratamiento de la nefropatía crónica. 4. Sujeto que se ha sometido, o que está en lista de espera, o que tiene previsto someterse a un trasplante de riñón o de otro órgano. 5. Accidente isquémico transitorio, ictus, angina inestable o infarto de miocardio conocidos y documentados en los seis meses previos a la selección. 6. Cardiopatía inestable de importancia clínica en opinión del investigador (p. ej., arritmia sintomática no controlada, insuficiencia cardíaca congestiva de clase III o IV de la New York Heart Association) 7. Cualquier otro sujeto con un riesgo elevado de presentar signos clínicos de afectación orgánica durante el período del estudio, a juicio del investigador. 8. Sujeto con inicio inminente previsto de un tratamiento con TSE. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is a response to study treatment on neuropathic pain, defined as a reduction from baseline to Month 6 of at least 30% in the "modified" Brief Pain Inventory-Short Form item 3 (BPI-SF3) score of "neuropathic pain at its worst in the last 24 hours". |
El criterio de valoración principal de la eficacia es la respuesta al tratamiento del estudio en el dolor neuropático, definida como una reducción entre el momento basal y el mes 6 de al menos el 30 % en la puntuación del BPI-SF3 «modificado» de «peor dolor neuropático en las últimas 24 horas». |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Month 6 |
De basal a los 6 meses |
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E.5.2 | Secondary end point(s) |
• Change from baseline to Month 6 in the average daily 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). |
• Variación entre el momento basal y el mes 6 del promedio de la puntuación diaria en la escala de valoración numérica de 11 puntos (EVN-11) del «peor dolor abdominal en las últimas 24 horas» en los sujetos con síntomas digestivos en el momento basal. • Variación entre el momento basal y el mes 6 de la cantidad de días con al menos una deposición de consistencia de tipo 6 o 7 en la escala de heces de Bristol (Bristol Stool Scale, BSS) en sujetos con síntomas digestivos en el momento basal. • Variación entre el momento basal y el mes 6 de la concentración plasmática de globotriaosilceramida (Gb3). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to Month 6 |
De basal a los 6 meses |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability |
tolerabilidad |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Canada |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Russian Federation |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS: 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. |
UVUS: Si el último sujeto entra en la fase de extensión abierta, el final del ensayo corresponderá a la visita de fin de tratamiento. Si el último sujeto no entra en la fase de extensión abierta, el fin del ensayo será la visita de seguimiento 2, seguimiento 2 o la última visita del periodo de observación posterior al tratamiento |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |