E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease |
Malattia di 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 malattia di Fabry è una patologia rara, ereditaria, causata da un difetto genetico che porta a accumulare sostanze grasse nel corpo. I sintomi includono dolore addominale e danni agli organi vitali |
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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 | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
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). |
Valutare gli effetti di Lucerastat sul dolore neuropatico in soggetti con la malattia di Fabry (FD). |
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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. |
• Valutare gli effetti di Lucerastat sui sintomi gastrointestinali (GI) (dolore addominale e diarrea) in soggetti con FD e i sintomi GI al baseline; • Confermare gli effetti di Lucerastat sui biomarcatori della FD; • Valutare la sicurezza e la tollerabilità di Lucerastat in soggetti con FD. |
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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 |
Other types of substudies Specify title, date and version of each substudy with relative 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.
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sarà condotto un sottostudio in tutti i centri per determinare il profilo di farmacocinetica di Lucerastat a uno stadio stabile in un sottogruppo di circa 36 soggetti con Malattia di Fabry sia con funzione renale normale che anormale (es. eGFR di screening = 60 mL/min/1,73 m2) o funzione renale ridotta (es. eGFR di screening > 60 mL/min/1,73 m2). Se necessario, i campioni di sangue raccolti per la farmacocinetica possono essere usati per l’identificazione dei metaboliti di Lucerastat in questa popolazione. I soggetti che acconsentono a questo sottostudio avranno un profilo di farmacocinetica di 12 ore alla visita del Mese 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 a- galactosidase A). 4. Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening. |
1. ICF sottoscritto e datato prima di qualsiasi procedura richiesta dallo studio. 2. Soggetti di sesso maschile e femminile di età pari o superiore ai 18 anni. 3. Diagnosi di FD confermata con i risultati dei test genetici locali (es. presenza di almeno 1 mutazione in GLA, la codifica del gene per a galattosidasi A [a-GalA]). 4. Dolore neuropatico associato alla malattia di Fabry, come definito dal soggetto, negli ultimi 3 mesi prima dello screening. |
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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. In gravidanza/in gravidanza programmata fino a 30 giorni dopo l’interruzione del trattamento di studio o soggetto in allattamento; 2. Insufficienza renale acuta definita come velocità di filtrazione glomerulare (eGFR) stimata mediante l’equazione della creatinina secondo la Chronic Kidney Disease Epidemiology Collaboration < 30 mL/min/1,73 m2 allo screening (come riportato dal laboratorio centrale); 3. Soggetto sottoposti regolarmente a dialisi per il trattamento dell’insufficienza renale cronica; 4. Il soggetto è stato sottoposto, o è in lista di attesa, o ha un trapianto programmato di reni o altri organi; 5. Attacco ischemico transitorio noto e documentato, ictus, angina instabile o infarto del miocardio nei 6 mesi prima dello screening; 6. Malattia cardiaca instabile clinicamente rilevante secondo lo sperimentatore (es. aritmia sintomatica instabile, insufficienza cardiaca congestizia di classe III o IV secondo la New York Heart Association); 7. Ogni altro soggetto ad alto rischio di sviluppo di segni clinici di coinvolgimento di organi nel periodo di durata dello studio, secondo il giudizio dello sperimentatore; 8. Il soggetto ha programmato di iniziare un trattamento con terapia enzimatica sostitutiva (ERT) nell’imminenza. |
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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". |
L’endpoint primario di efficacia è una risposta al trattamento di studio del dolore neuropatico, definito come riduzione dal baseline al Mese 6 di almeno il 30% nel risultato “modificato” BPI-SF3 del “dolore neuropatico al suo punto massimo nelle ultime 24 ore”. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Month 6 |
Dal baseliine al Mese 6 |
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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). |
• Variazioni dal baseline al Mese 6 nel risultato della scala di valutazione numerica media quotidiana a 11-punti (NRS-11) di “dolore addominale al suo punto massimo nelle ultime 24 ore” in soggetti con sintomi GI al baseline. • Variazioni dal baseline al Mese 6 nel numero di giorni con almeno un episodio di feci, secondo la Bristol Stool Scale (BSS), di consistenza di Tipo 6 o 7 in soggetti con sintomi GI al baseline; • Variazioni dal baseline al Mese 6 di globotriaosilceramide (Gb3) nel plasma. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to Month 6 |
Dal baseline al Mese 6 |
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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 |
Tollerabilità |
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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 | 3 |
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 | Information not present in EudraCT |
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 |
Finland |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
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. |
LVLS: Se l’ultimo soggetto partecipa allo studio di estensione in aperto (OLE), la durata complessiva dello studio corrisponde alla visita EOT dell’ultimo soggetto. Se l’ultimo soggetto non partecipa allo studio OLE, la durata complessiva dello studio corrisponde all’ultima visita di follow up di sicurezza post-trattamento (FU1) del soggetto, alla visita FU2, o all’ultima visita del periodo di osservazione post-trattamento (PTOP), qualunque sia l’ultima. |
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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 | 1 |
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 |