E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease (α-galactosidase A deficiency) |
Enfermedad de Fabry (déficit de alfa-galactosidasa) |
|
E.1.1.1 | Medical condition in easily understood language |
Fabry disease (α-galactosidase A deficiency) |
Enfermedad de Fabry (déficit de alfa-galactosidasa) |
|
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. |
Evaluar los parámetros de seguridad, tolerabilidad y eficacia en curso de 1 mg/kg de pegunigalsidasa alfa (PRX-102) cada dos semanas en pacientes adultos con la enfermedad de Fabry que han completado satisfactoriamente los estudios PB-102-F20 o PB-102-F30. |
|
E.2.2 | Secondary objectives of the trial |
|
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
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. Finalización del estudio PB-102-F20 o PB-102-F30
2. El paciente firma el consentimiento informado
3. Pacientes de sexo femenino y masculino cuyas parejas estén en edad fértil y acepten el uso de un método anticonceptivo altamente eficaz aceptable desde el punto de vista médico, sin incluir el método del ritmo. Los métodos anticonceptivos aceptables incluyen productos hormonales, dispositivos intrauterinos o condones masculinos o femeninos. La anticoncepción debe usarse durante 1 mes después de la finalización del tratamiento. |
|
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. |
1. Presencia de cualquier problema médico, emocional, conductual o psicológico que, a juicio del investigador y/o del director médico, interferiría en el cumplimiento del paciente de los requisitos del estudio. |
|
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 |
CRITERIOS DE VALORACIÓN DE LA SEGURIDAD:
Cambios desde el inicio en:
• Análisis clínicos
• Exploración física
• Evaluación de la zona de inyección
• Electrocardiograma (ECG)
• Acontecimientos adversos surgidos durante el tratamiento (AAST)
• Capacidad para disminuir de forma gradual la premedicación para la infusión al inicio del estudio
• Requisito de uso de la premedicación en general para tratar las reacciones a la infusión
• Anticuerpos contra la pegunigalsidasa alfa surgidos durante el tratamiento |
|
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. |
Los pacientes que reciban al menos una dosis del fármaco del estudio se incluirán en el análisis de la seguridad. Se resumirán y describirán los resultados de las evaluaciones de seguridad (incluidos AAST, reacciones en la zona de la inyección, exploraciones físicas, ECG, pruebas analíticas y anticuerpos antifármaco). No se realizarán análisis estadísticos formales en este estudio. Los criterios de valoración del estudio se evaluarán por diversos análisis resumidos por visita del estudio y por el cambio con respecto a los datos del inicio de cada criterio de valoración de la eficacia. Se compararán los criterios de valoración de seguridad y eficacia con respecto al inicio mediante estadísticas resumidas. Los datos no se analizarán mediante estadística inferencial. *Consultar Protocolo |
|
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 Gb3
*Plasma Lyso-Gb3
*Urine Lyso-Gb3
*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)
*Clinical events |
CRITERIOS DE VALORACIÓN DE LA EFICACIA:
* Tasa de filtración glomerular estimada (TFGeCKD-EPI)
*Índice de masa del ventrículo izquierdo (g/m2) mediante imágenes de resonancia magnética (IRM)
* Gb3 en plasma
* Lyso-Gb3 en plasma
* Lyso-Gb3 en orina
* Cociente proteínas/creatinina en prueba puntual de orina
* Frecuencia de uso de analgésicos
* Tolerancia al ejercicio (prueba de esfuerzo)
* Cuestionario abreviado para la evaluación del dolor (Brief Pain Inventory, BPI)
* Índice de valoración de la gravedad de Mainz (Mainz Severity Score Index, MSSI)
* Calidad de vida (EQ-5D-5L)
* Eventos clínicos |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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 | No |
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
| 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 | 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 | 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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Slovenia |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
|
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
|
LVLS |
Ultimo paciente ultima visita |
|
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 |