E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome) |
Mucopolisacaridosis de tipo VII (MPS VII, síndrome de Sly) |
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E.1.1.1 | Medical condition in easily understood language |
Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome) |
Mucopolisacaridosis de tipo VII (MPS VII, síndrome de Sly) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
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 |
The primary objective is to evaluate the effect of UX003 treatment in pediatric MPS 7 subjects less than 5 years of age on: -Safety and tolerability -Efficacy as determined by the reduction of uGAG excretion |
El objetivo principal consiste en evaluar el efecto del tratamiento con UX003 en pacientes pediátricos con MPS VII menores de 5 años de edad en: -Seguridad y tolerabilidad -La eficacia según lo determinado por la reducción de la excreción de GAG (GAGu) |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the effect of UX003 on growth velocity and hepatosplenomegaly. |
El objetivo secundario es evaluar el efecto de UX003 en la velocidad de crecimiento y en la hepatoesplenomegalia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay, or genetic testing -Under 5 years of age at the time of informed consent -Written informed consent of Legally Authorized Representative after the nature of the study has been explained, and prior to any research-related procedures |
-Diagnóstico confirmado de MPS VII sobre la base de la determinación enzimática de glucuronidasa en leucocitos o fibroblastos o del análisis genético. -Menores de 5 años de edad en el momento del consentimiento informado. -Consentimiento informado por escrito del representante legalmente autorizado después de haberse explicado la naturaleza del estudio y antes de cualquier procedimiento relacionado con el estudio. |
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E.4 | Principal exclusion criteria |
-Undergone a successful bone marrow or stem cell transplant or has evidence of any degree of detectable chimaerism with donor cells -Any known hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects -Use of any investigational product (drug or device or combination) other than UX003 within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments at any time during the study -Has a condition of such severity and acuity, in the opinion of the Investigator, which may not allow safe study participation. For patients with hydrops fetalis, the ongoing interventions to manage fluid balance can be continued; if the addition of ERT is considered a fluid-overload risk, the individual should be excluded. -Has a concurrent disease or condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or affect safety. Since hydropic patients have a high rate of mortality, the risk of death prior to 1 year of age should not be considered sufficient to exclude the patient from the study for compliance. |
-Se ha sometido a un trasplante exitoso de médula ósea o células madre, o tiene signos de algún grado de quimerismo detectable con células del donante. -Cualquier hipersensibilidad conocida a la rhGUS o sus excipientes que, en opinión del investigador, aumenta el riesgo del paciente de sufrir efectos adversos. -Uso de un producto en investigación (medicamento o dispositivo, o combinación) distinto de UX003 dentro de los 30 días anteriores a la selección o necesidad de un fármaco en investigación antes de finalizar todas las evaluaciones programadas del estudio en cualquier momento durante su transcurso. -Tiene una afección cuya gravedad y carácter agudo podría no permitir, en opinión del investigador, la participación segura en el estudio. En los pacientes con hidropesía fetal pueden continuar las intervenciones en curso para controlar el balance hídrico. El paciente se excluirá del estudio si se considera que añadir el TSE representa un riesgo de sobrecarga de líquidos. -Tiene una enfermedad o un trastorno concurrente que, en opinión del investigador, pone al paciente en un alto riesgo de no cumplir adecuadamente con el tratamiento, de no completar el estudio o que podría interferir en la participación en el estudio o comprometer la seguridad. Como la tasa de mortalidad es alta en los pacientes con hidropesía, el riesgo de muerte antes de 1 año de edad no debe considerarse motivo suficiente para excluir al paciente del estudio por problemas de cumplimiento |
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E.5 End points |
E.5.1 | Primary end point(s) |
Urinary GAG Excretion: the mean percent change in uGAG excretion from Week 0 to Week 48. |
Excreción de GAG urinarios: cambio en el porcentaje de excreción media de GAGu entre la semana 0 y la semana 48. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Urinary GAG Excretion: Urine samples will be collected every other visit up to Week 12, then every 6 weeks to Week 48, then every 12 weeks to Week 240. And 2 samples will be collected during the baseline week. |
Excreción de GAG urinarios: Las muestras de orina se recogerán cada 2 visitas hasta visita de semana 12, después cada 6 semanas hasta visita semana 48, después cada 12 semanas hasta visita de semana 240. Y se recogerán 2 muestras en la visita basal. |
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E.5.2 | Secondary end point(s) |
Growth and hepatosplenomegaly will be evaluated to compare pretreatment with post treatment effects |
El crecimiento y la hepatoesplenomegalia se evaluarán para comparar los efectos pre-tratamiento con los efectos post-tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-For growth: anthropometrics will be measured every 12 weeks from baseline to Week 240, -For liver/spleen size: will be measured at baseline, Week 12, 24, 48, then every 48 weeks to Week 240 |
-Para crecimiento: las medidas antropométricas se realizarán cada 12 semanas desde visita basal hasta visita de semana 240. -Para el tamaño de hígado/bazo: Se tomarán medidas en visita basal, semana 12, 24, 48 y después cada 48 semanas hasta la visita de semana 240. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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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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LVLS |
Última visita del último paciente |
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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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |