E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glycogen storage disease type II |
Glucogenosis tipo II |
|
E.1.1.1 | Medical condition in easily understood language |
Glycogen storage disease type II |
Glucogenosis tipo II |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053185 |
E.1.2 | Term | Glycogen storage disease type II |
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 avalglucosidase alfa treatment on survival and invasive ventilator-free survival of IOPD participants less than or equal to 6 months of age after 52 weeks of treatment. |
Determinar el efecto del tratamiento con avalglucosidasa alfa en la supervivencia y la supervivencia sin respirador invasivo de los participantes con EPII de ≤6 meses de edad después de 52 semanas de tratamiento |
|
E.2.2 | Secondary objectives of the trial |
- To determine the effect of avalglucosidase alfa treatment on survival and invasive ventilator-free survival at 12 and 18 months of age, as well as the change in left ventricular mass Z-score (LVM Z-score); Alberta Infant Motor Scale (AIMS) score; body length, body weight, and head circumference Z scores; and urinary Hex4 at Week 52 in IOPD participants less than or equal to 6 months of age - To determine safety, tolerability, and immunogenicity of avalglucosidase alfa - To determine the PK profile at Week 12 and Week 52 |
- Determinar el efecto del tratamiento con avalglucosidasa alfa sobre la supervivencia y la supervivencia libre de ventilación invasiva a los 12 y 18 meses de edad, así como el cambio en la puntuación LVM-Z; la puntuación AIMS; la puntuación Z de la longitud corporal, el peso corporal y el perímetro cefálico; y concentraciones urinarias de Hex4 en la semana 52 en participantes con EPII de ≤6 meses de edad. - Determinar la seguridad, tolerabilidad e inmunogenicidad de avalglucosidasa alfa. - Determinar el perfil FC en la semana 12 y en la semana 52 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants must have confirmed diagnosis of infantile-onset Pompe disease defined as: the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a documented GAA deficiency from blood, skin, or muscle tissue; or the presence of 1 GAA pathogenic variant and a documented GAA deficiency from blood, skin and muscle tissue in 2 separate samples (from either 2 different tissues or from the same tissue but at 2 different sampling dates). - Participants must have established cross-reactive immunological material (CRIM) status available prior to enrollment. - Participants must have cardiomyopathy at the time of diagnosis: ie, left ventricular mass index (LVMI) equivalent to mean age specific LVMI +1 standard deviation for participants diagnosed by newborn screening or sibling screening; +2 standard deviation for participants diagnosed by clinical evaluation. - Parents or legally authorized representative(s) must be capable of giving signed informed consent |
- Los participantes deben tener un diagnóstico confirmado de enfermedad de Pompe de inicio en la infancia definido como: la presencia de 2 variantes patógenas de GAA y una deficiencia documentada de GAA en la sangre (las muestras de sangre seca se consideran aceptable); piel o tejido muscular; o la presencia de 1 variante patógena de GAA y una deficiencia documentada de GAA en la sangre, piel y tejido muscular en 2 muestras separadas (de 2 tejidos diferentes o del mismo tejido, pero en 2 fechas de obtención de muestra diferentes. - Los participantes deben haber establecido el estado de material inmunológico con reactividad cruzada (CRIM) disponible antes de la inclusión. - Los participantes deben tener miocardiopatía en el momento del diagnóstico: es decir, IMVI equivalente al IMVI específico de la edad media +1 de desviación estándar para los participantes diagnosticados por cribado de recién nacidos o cribado de hermanos; +2 de desviación estándar para los participantes diagnosticados mediante evaluación clínica. - Los progenitores o representantes legales aceptables deben poder otorgar el consentimiento informado firmado |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - Participants with symptoms of respiratory insufficiency, including any ventilation use (invasive or noninvasive) at the time of enrollment. - Participants with major congenital abnormality. - Participants with clinically significant organic disease (with the exception of symptoms relating to Pompe disease). - Participant received any Pompe disease specific treatment, eg ERT gene therapy. - Participant who has previously been treated in any clinical trial of avalglucosidase alfa. - Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures. |
- Participantes con síntomas de insuficiencia respiratoria, incluidos cualquier uso de respiración asistida (invasiva o no invasiva). - Participantes con anomalías congénitas importantes. - Los participantes tienen una enfermedad orgánica de importancia clínica (a excepción de los síntomas relacionados con la enfermedad de Pompe). - El participante recibió cualquier tratamiento específico para la enfermedad de Pompe, p. ej., TRE, genoterapia. - Participante que ha sido tratado previamente en cualquier ensayo clínico de avalglucosidasa alfa. - Participantes que, a criterio del investigador, no sean idóneos para participar, independientemente del motivo, incluido el estado clínico o médico, o participantes que posiblemente no cumplan los procedimientos del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants who are alive and free of invasive ventilation at Week 52 |
Proporción de participantes vivos y sin ventilación invasiva en la Semana 52 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1/ Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age
2/ Proportion of participants who are alive at Week 52
3/ Proportion of participants who are alive at 12 and 18 months of age
4/ Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52
5/ Proportion of participants who are free of supplemental oxygen use at Week 52
6/ Change from baseline to Week 52 in left ventricular mass (LVM)-Z score
7/ Change from baseline to Week 52 in Alberta Infant Motor Scale (AIMS) score
8/ Change from baseline to Week 52 in body length Z-scores
9/ Change from baseline to Week 52 in body weight Z-scores
10/ Change from baseline to Week 52 in head circumference Z-scores
11/ Change from baseline to Week 52 in body length percentiles
12/ Change from baseline to Week 52 in body weight percentiles
13/ Change from baseline to Week 52 in head circumference percentiles
14/ Change from baseline to Week 52 in urinary Hex4
15/ Assessment of treatment-emergent adverse events (TEAE) including infusion-associated reactions (IAR)
16/ Physical examination
17/ Clinical laboratory evaluations
18/ Vital signs measurements
19/ 12-lead electrocardiogram (ECG)
20/ Immunogenicity assessments
21/ Plasma concentration of avalglucosidase alfa |
1. Proporción de participantes vivos y sin ventilación invasiva a los 12 y 18 meses de edad 2. Proporción de participantes vivos en la semana 52 3. Proporción de participantes vivos a los 12 y 18 meses de edad 4. Proporción de participantes sin uso de respirador (invasivos y no invasivos, por separado y combinados) en la Semana 52. 5. Proporción de participantes sin uso de oxígeno suplementario en la semana 52 6. Cambio con respecto al momento inicial hasta la semana 52 en la puntuación Z de la MVI 7. Cambio con respecto al momento inicial hasta la semana 52 en la puntuación AIMS 8. Cambio con respecto al momento inicial hasta la semana 52 en las puntuaciones Z de la longitud corporal 9. Cambio con respecto al momento inicial hasta la semana 52 en las puntuaciones Z del peso corporal 10. Cambio con respecto al momento inicial hasta la semana 52 en las puntuaciones Z del perímetro cefálico 11. Cambio con respecto al momento inicial hasta la semana 52 en los percentiles de la longitud corporal 12. Cambio con respecto al momento inicial hasta la semana 52 en los percentiles del peso corporal 13. Cambio con respecto al momento inicial hasta la semana 52 en los percentiles del perímetro cefálico 14. Cambio con respecto al momento inicial hasta la semana 52 en las concentraciones urinarias de Hex4 15. Evaluación de AADT, incluidas las RAI 16. Exploración física 17. Análisis de laboratorio clínico 18. Mediciones de las constantes vitales 19. ECG de 12 derivaciones 20. Evaluaciones de inmunogenicidad 21. Concentración plasmática de avalglucosidasa alfa |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/, 3/: at 12 and 18 months of age
2/ and from 4/ to 14/ : Week 52
15/: week 52, week 212
From 16/ to 20/: Week 52, Week 208
21/ : at Day 1, Week 12, and Week 52 |
1/, 3/: a los 12 y 18 meses de edad.
2/ and from 4/ to 14/ semana 52
15/: semana 52, semana 212
Desde 16/ a 20/: Semana 52, semana 208
21/ : Día 1, semana 12, semana 52 |
|
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 | 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 | No |
E.8.1.2 | Open | No |
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 | 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 |
China |
Taiwan |
United States |
France |
Netherlands |
Germany |
Italy |
Belgium |
United Kingdom |
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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
|
LVLP |
La última visita del último paciente |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |