E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the gene (GLA) that encodes the lysosomal enzyme alfa-galactosidase A. |
La enfermedad de Fabry es una enfermedad rara del almacenamiento lisosomal ligada al cromosoma X causada por mutaciones en el gen GLA que codifica la enzima lisosomal, alfa-galactosidasa A. |
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E.1.1.1 | Medical condition in easily understood language |
Fabry disease is an inherited disorder that results from the buildup of a particular type of fat in the body's cells. |
La enfermedad de Fabry es un deorden inherente que resulta en la acumulación de un tipo particular de grasas en las células del cuerpo. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 assess long-term safety of migalastat HCl in the treatment of subjects with Fabry disease who completed treatment in a previous study of migalastat HCl. |
Determinar la seguridad a largo plazo del migalastat HCl en el tratamiento de sujetos con enfermedad de Fabry que hayan completado el tratamiento en un estudio previo con migalastat HCl. |
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E.2.2 | Secondary objectives of the trial |
To explore long-term efficacy/pharmacodynamics of migalastat HCl in subjects with Fabry disease who have completed treatment in a previous study of migalastat HCl. |
Explorar la eficacia y la farmacodinamia a largo plazo del migalastat HCl en sujetos con enfermedad de Fabry que hayan completado el tratamiento en un estudio previo con migalastat HCl. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subject with Fabry disease who completed treatment in a previous study of migalastat HCl given as monotherapy.
2. Male or female subjects 16 years of age or older. Note: Subjects under the age of 18 will be enrolled only at sites with all required regulatory and ethics approvals to do so.
3. A female subject is eligible to participate if she is: A. Of non-childbearing potential, or B. Of childbearing potential and NOT pregnant or nursing, has a negative urine pregnancy test at the Baseline Visit (Visit 1), and agrees to one of the methods of avoiding pregnancy listed in Appendix 1 as per the study protocol from the time of first dose of study medication until 30 days after study completion. A female is considered Non-childbearing potential if she is status-post hysterectomy, status-post surgical removal of both ovaries, has current, documented tubal ligation, or is postmenopausal and >2 years without menses. Female subjects who are post-menopausal <2 years must be confirmed menopausal by Follicle Stimulating Hormone (FSH) and estradiol levels. A female is considered childbearing potential if she has functional ovaries, ducts, and uterus with no impairment that would cause sterility. This includes women with oligomenorrhea (even severe), and women who are perimenopausal or who have just begun to menstruate.
4. Male subjects must agree to use one of the contraception methods listed in Appendix 1. This criterion must be followed from the time of the first dose of study medication until 30 days after study completion.
5. Subject is willing and able to provide written informed consent and authorization for use and disclosure of Personal Health Information (PHI) or has a legally authorized representative who has given written informed consent.
6. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
1.Sujeto con enfermedad de Fabry que haya completado el tratamiento en un estudio previo con migalastat HCl administrado en monoterapia. 2.Mujeres o varones de 16 años de edad en adelante.Nota: los sujetos de menos de 18 años de edad se incluirán exclusivamente en los centros que cumplan todas las aprobaciones administrativas y éticas exigidas para ello. 3.Las mujeres podrán participar siempre que: a)No estén en edad fértil; o b) estén en edad fértil y NO estén embarazadas ni en periodo de lactancia, dispongan de una prueba de embarazo negativa en orina en la visita basal (visita 1) y acepten uno de los métodos anticonceptivos recogidos en el Apéndice 1 desde el momento de recibir la primera dosis del fármaco del estudio hasta 30 días después de la finalización del estudio.Una mujer se considera que no se encuentra en edad fértil si se ha sometido a histerectomía, ovariectomía bilateral o ligadura de trompas documentada o es postmenopáusica y carece de menstruaciones desde hace > dos años. Las mujeres postmenopáusicas sin menstruación desde < de dos años deben confirmar su estado a partir de los niveles de hormona foliculina (FSH) y estradiol. Una mujer se considera en edad fértil si tiene ovarios funcionales, trompas y útero intactos, sin ningún daño que pudiera causar esterilidad. Se incluyen aquí mujeres con oligomenorrea (incluso intensa) y mujeres que se encuentren en periodo perimenopáusico o que hayan comenzado la menstruación. 4.Los varones deben aceptar el uso de uno de los métodos contraceptivos recogidos en el Apéndice 1. Este criterio debe mantenerse desde el momento de la administración de la primera dosis de la medicación del estudio hasta 30 días después de la finalización del estudio. 5.El sujeto está dispuesto y es capaz de otorgar el consentimiento informado y la autorización por escrito para el uso y publicación de su información de salud personal (ISP) o dispone de un representante legal autorizado que ha otorgado el consentimiento informado. 6. Pacientes franceses: en Francia un sujeto será considerado apto para participar en este estudio sólo si está afiliado o es beneficiario de la seguridad social. |
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E.4 | Principal exclusion criteria |
1. The last available estimated glomerular filtration rate (eGFR) in the previous study was <30 mL/min/1.73m2; unless there is measured GFR available within 3 months of Baseline Visit (Visit 1), which is >30 mL/min/1.73m2.
2. The subject has undergone, or is scheduled to undergo kidney transplantation or is currently on dialysis.
3. The subject is treated or has been treated with another investigational drug (except migalastat HCl) within 30 days of study start.
4. Subject is unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator. |
1. La última FGe disponible del estudio previo fue <30 ml/min/1,73 m2, a menos que se disponga de una FG medida de los 3 meses previos a la visita basal (visita 1) >30 ml/min/1,73 m2. 2.El sujeto se ha sometido o va a someterse a un transplante renal o se encuentra actualmente en diálisis. 3. El sujeto está recibiendo o ha recibido otro fármaco en investigación (salvo migalastat HCl) en los 30 días previos al comienzo del estudio. 4.El sujeto es incapaz de cumplir los requisitos del estudio, o el investigador lo juzga no apto para la inclusión. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The safety assessments are: - Adverse events (AEs), Possible Suicidality Related AEs (PSRAEs) and serious adverse events (SAEs) - Withdrawal due to AEs - Vital signs (blood pressure and heart rate) and body weight -Hematology, chemistry, and urinalysis parameters -Echocardiography (ECHO) -Electrocardiograms (ECGs) |
Las evaluaciones de la seguridad comprenden lo siguiente: - Acontecimientos adversos (AA), acontecimientos adversos relacionados con posibles ideas suicidas (AARPIS) y acontecimientos adversos graves (AAG). - Retirada debida a AA. - Constantes vitales (presión arterial y frecuencia cardiaca) y peso. - Hematología, bioquímica y parámetros del análisis de orina. - Ecocardiografía (ECO). - Electrocardiogramas (ECG). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs will be collected from the start of study treatment (i.e., Visit 1) and until the follow-up contact. |
AAs se recogerán desde el comienzo del tratamiento del estudio (pe visita 1) y hasta el contacto de seguimiento. |
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E.5.2 | Secondary end point(s) |
The efficacy/pharmacodynamic assessments are: - Estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease (MDRD) equation. - Measurement of 24-hour urine protein - Evaluation of left ventricular mass index (LVMi ), as measured by echocardiography - Ejection fraction, as measured by echocardiography - Evaluation of urine globotriaosylceramide (GL-3) from 24-hour urine collection - Evaluation of leukocyte alfa-galactosidase A (alfa-Gal A) activity - Evaluation of patient reported assessment of pain as assessed by the Brief Pain Inventory (BPI) short form - Evaluation of patient reported Quality of Life as assessed by the Short Form -36 survey (SF-36). |
Las evaluaciones de la eficacia y la farmacodinamia son: - FG estimada (FGe) basada en la ecuación modificación de la dieta en las nefropatías (MDRD). - Determinación de proteínas en la orina de 24-horas. - Medición del índice de masa del ventrículo izquierdo (índice MVI) mediante ecocardiografía. -Determinación de la fracción de eyección mediante ecocardiografía. -Determinación de globotriaosilceramida (GL-3)en orina recogida en 24h. -Determinación de la actividad leucocitaria de alfa-galactosidasa ( alfa-Gal A). -Evaluación de la intensidad del dolor comunicada por el paciente mediante el cuestionario abreviado del inventario del dolor (BPI). -Evaluación de la calidad de vida realizada por el paciente mediante el cuestionario abreviado de 36 preguntas (SF-36). Para cada criterio de valoración de la eficacia se evaluará el cambio desde el momento basal, definido (como en la tabla 1 del protocolo) como el valor obtenido en la última visita de tratamiento del estudio previo de migalastat HCl. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from baseline will be evaluated for each efficacy endpoint, where baseline is defined (as in Table 1 of the study protocol) as the value from the last treatment visit of the previous migalastat HCl study. |
Para cada criterio de valoración de la eficacia se evaluará el cambio desde el momento basal, definido (como en la tabla 1 del protocolo) como el valor obtenido en la última visita de tratamiento del estudio previo de migalastat HCl. |
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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 | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Brazil |
Denmark |
Egypt |
France |
Italy |
Spain |
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
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The duration of the treatment will vary among subjects. Within each participating country, subjects may continue to receive treatment with migalastat HCl within this protocol until one of the study conclusion conditions listed in section 3.1 of the study protocol apply. This protocol will be open until the end of 2016, after which time the continued utility of the study will be evaluated by the sponsor. |
La duración del tratamiento variará entre los sujetos. En cada uno de los países participantes, los sujetos pueden continuar recibiendo tratamiento con migalastat HCl con arreglo al protocolo hasta que se produzca una de las situaciones listadas en la sección 3.1 del protocolo. Este protocolo se mantendrá activo hasta finales de 2016, momento en que el promotor evaluará si está justificado continuar el estudio. |
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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 | 5 |
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 | 5 |
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 |