E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease (a-galactosidase A deficiency) |
Malattia di Fabry (deficienza di a- galattosidasi A) |
|
E.1.1.1 | Medical condition in easily understood language |
Fabry disease (a-galactosidase A deficiency) |
Malattia di Fabry (deficienza di a- galattosidasi A) |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
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 |
|
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 evaluate the ongoing safety, tolerability, and efficacy parameters of 1 mg/kg pegunigalsidase alfa (PRX-102) every other week in adult Fabry patients who have successfully completed studies PB-102-F20 or PB-102-F30, or completed at least 48 months in study PB-102-F03. |
Valutare i parametri continui di sicurezza, tollerabilità ed efficacia di pegunigalsidasi alfa (PRX-102) 1 mg/kg ogni due settimane in pazienti adulti affetti da malattia di Fabry che abbiano completato con successo lo studio PB-102-F20 o PB-102-F30 oppure abbiano completato almeno 48 mesi dello studio PB-102-F03 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completion of study PB-102-F20 or PB-102-F30, or completed at least 48 months in study PB-102-F03.
2. The patient signs informed consent
3. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method. Acceptable methods of contraception include hormonal products, intrauterine device, or male or female condoms. Contraception should be used for 1 month after treatment termination. |
1. Completamento dello studio PB-102-F20 o PB-102-F30, oppure completamento di almeno 48 mesi dello studio PB-102-F03. 2. Firma da parte del paziente del consenso informato 3. Consenso delle pazienti e dei pazienti con compagne in età fertile a utilizzare un metodo contraccettivo accettabile dal punto di vista medico, ad esclusione del metodo Ogino-Knaus. I metodi contraccettivi accettabili comprendono prodotti ormonali, dispositivo intrauterino o preservativi maschili o femminili. La contraccezione deve proseguire per 1 mese dopo la conclusione del trattamento. |
|
E.4 | Principal exclusion criteria |
1. Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with patient compliance with the requirements of the study. |
Presenza di qualsiasi condizione medica, emotiva, comportamentale o psicologica che, a giudizio dello sperimentatore e/o del Dirigente Medico, potrebbe interferire con la conformità del paziente ai requisiti dello studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
SAFETY ENDPOINTS:
Changes from baseline in:
*Clinical laboratory tests
*Physical examination
*Assessment of the injection site
*Electrocardiography (ECG)
*Treatment-emergent adverse events (TEAE)
*Ability to taper off infusion pre-medication at the start of the study
*Requirement for use of pre-medication overall to manage infusion reactions
*Treatment-emergent anti-pegunigalsidase alfa antibodies |
Variazioni rispetto al basale in: *Analisi cliniche di laboratorio *Esame obiettivo *Valutazione della sede di iniezione *Elettrocardiogramma (ECG) *Eventi avversi emergenti dal trattamento (TEAE) *Possibilità di ridurre la premedicazione all’infusione all’avvio dello studio *Necessità di utilizzare complessivamente una premedicazione per gestire le reazioni all’infusione *Anticorpi anti-pegunigalsidasi alfa emergenti dal trattamento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients who received at least one dose of study drug will be included in the safety analysis. Results of safety evaluations (including TEAEs, injection site reactions, physical examinations, ECG, and laboratory analyses, anti-drug antibodies) will be summarized and described.
No formal statistical analyses will be performed. The study endpoints will be evaluated by various summary analyses by study visit and by change from baseline data for each efficacy endpoint. Safety and efficacy endpoints will be compared to baseline using summary statistics. Data will not be analysed by inferential statistics.
An interim analysis may be performed for administrative purposes during the course of the study; available efficacy and safety parameters will be summarized using descriptive statistics. |
L’analisi di sicurezza includerà pazienti che hanno ricevuto almeno una dose di farmaco. Saranno descritti i risultati delle valutazioni di sicurezza compresi TEAE reazioni nella sede di iniezione esami obiettivi ECG analisi di laboratorio anticorpi anti-farmaco. Non verranno eseguite analisi statistiche formali Gli endpoint saranno valutati con analisi riassuntive per visita dello studio e variazione rispetto ai dati al basale per ciascun endpoint di efficacia. Gli endpoint di efficacia e sicurezza saranno confrontati al basale tramite statistiche descrittive I dati non saranno analizzati tramite statistiche inferenziali Durante lo studio potrebbe essere eseguita un’analisi ad interim per finalità amministrative con statistiche descrittive per riassumere parametri di efficacia e sicurezza |
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E.5.2 | Secondary end point(s) |
EFFICACY ENDPOINTS:
*Estimated glomerular filtration rate (eGFRCKD-EPI)
*Left Ventricular Mass Index (g/m2) by magnetic resonance imaging (MRI)
*Plasma Lyso-Gb3
*Plasma Gb3 concentration
*Protein/Creatinine ratio, spot urine test (UPCR)
*Frequency of pain medication use
*Exercise tolerance (Stress Test)
*Short Form Brief Pain Inventory (BPI)
*Mainz Severity Score Index (MSSI)
*Quality of life (EQ-5D-5L)
*Fabry disease clinical events
|
*Velocità di filtrazione glomerulare stimata (eGFR mediante CKD-EPI) *Indice di massa ventricolare sinistra (g/m2) misurato mediante risonanza magnetica (RM) *Livelli plasmatici di liso-Gb3 *Concentrazione plasmatica di Gb3 *Rapporto proteine/creatinina nell’analisi su campione estemporaneo di urina (UPCR) *Frequenza dell’uso di farmaci analgesici *Tolleranza all’esercizio (test da sforzo) *Breve inventario per la valutazione del dolore (BPI) in forma abbreviata *Indice del punteggio di gravità di Mainz (MSSI) *Questionario europeo sulla qualità della vita a 5 dimensioni e 5 livelli (EQ-5D-5L) *Eventi clinici di malattia di Fabry |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Czech Republic |
Hungary |
Italy |
Netherlands |
Norway |
Slovenia |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |