E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal Muscular Atrophy (SMA) |
Atrofia Muscular Espinal |
|
E.1.1.1 | Medical condition in easily understood language |
Spinal Muscular Atrophy (SMA) |
Atrofia Muscular Espinal |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041582 |
E.1.2 | Term | Spinal muscular atrophy |
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 examine the clinical efficacy of ISIS 396443 administered intrathecally to patients with infantile-onset SMA. |
Examinar la eficacia clínica de ISIS 396443 administrado por vía intratecal a pacientes con SMA de inicio en edad infantil |
|
E.2.2 | Secondary objectives of the trial |
To examine the safety and tolerability of ISIS 396443 administered intrathecally to patients with infantile-onset SMA. |
Examinar la seguridad y tolerabilidad de ISIS 396443 administrado por vía intratecal a pacientes con SMA de inicio en edad infantil |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Be 7 months (210 days) of age or younger at screening
? Be born between 37 and 42 weeks
? Be medically diagnosed with spinal muscular atrophy (SMA) and have SMN2 Copy # of 2
? Be able to follow all study procedures
? Reside within 9 hours ground travel each way, for the duration of the study
? Meet additional study-related criteria
. Body weight ? 3rd percentile for age using appropriate country-specific guidelines
. Genetic documentation of 5q SMA homozygous gene deletion, homozygous mutation, or compound heterozygote |
. Ser ?7 meses (210 días) de edad en el momento de la selección.
. Edad gestacional de 37 a 42 semanas
. Ser diagnosticado con atrofia muscular espinal y tener Cantidad de copias de SMN2 = 2
.Poder completar todos los procedimientos del estudio
. Residir a una distancia que no supere, aproximadamente, las 9 horas de viaje en trasporte terrestre hasta un centro del estudio
. Cumplir los criterios adicionales del estudio.
. Peso corporal ?3.er percentil de edad utilizando guías adecuadas específicas para el país
. Documentación genética de la deleción del gen homocigota 5q SMA, mutación homocigota o heterocigota compuesta |
|
E.4 | Principal exclusion criteria |
. Hypoxemia (O2 saturation awake <96% or O2 saturation asleep <96%, without ventilation support) during screening evaluation
. Signs or symptoms of SMA present at birth or within the first week after birth
.Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period
.History of brain or spinal cord disease that would interfere with the LP procedures, CSF circulation, or safety assessments
.Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
.Subject?s caregiver is not willing to continue to meet standard of care guidelines for care (including vaccinations and RSV prophylaxis if available), nutritional and respiratory support throughout the duration of the study
.Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the subject unsuitable for inclusion |
. Hipoxemia (saturación de O2 despierto <96 % o saturación de O2 dormido <96 %, sin apoyo ventilatorio con aire ambiente) durante la evaluación de selección
. Signos o síntomas de SMA presentes al momento del nacimiento o en el plazo de la primera semana después del nacimiento
. Presencia de una infección activa no tratada o tratada inadecuadamente que requiere terapia antiviral o antimicrobiana sistémica en cualquier momento durante el período de selección.
. Antecedente de enfermedad cerebral o medular que interferirían con los procedimientos de PL, circulación del LCR o evaluaciones de la seguridad.
. Presencia de una derivación implantada para el drenaje de LCR o de un catéter implantado en el sistema nervioso central (SNC)
. El cuidador del sujeto no desea continuar cumpliendo los estándares de las guías de cuidados para el cuidado (incluye las vacunaciones y la profilaxis contra RSV, si estuviera disponible), la nutrición y el soporte respiratorio durante todo el estudio
. Alteraciones clínicamente significativas en los parámetros de hematología o química clínica, según lo evaluado por el investigador del centro, en la selección, que provocaría que el sujeto fuera inadecuado para la inclusión |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to death or permanent ventilation [?16 hours ventilation/day continuously for >21 days in the absence of an acute reversible event OR tracheostomy] |
Tiempo hasta la muerte o la ventilación permanente [?16 horas de ventilación/día continuamente durante >21 días en ausencia de un acontecimiento agudo reversible (Apéndice E) O traqueostomía] |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
? Change from baseline in CHOP-INTEND infant motor function scale at 13 months
? Change from baseline in motor milestones at 13 months
? Percent of subjects not requiring permanent ventilation over 13 months
? Survival rate over 13 months
? Time to death or permanent ventilation in the subgroups of subjects below the study median disease duration
? Time to death or permanent ventilation in the subgroups of subjects above the study median disease duration |
? Cambio con respecto al inicio en la escala de función motora del lactante CHOP-INTEND a los 13 meses
? Cambio con respecto al inicio en los hitos de la motricidad a los 13 meses
? Porcentaje de sujetos que no requieren ventilación permanente a los 13 meses
? Tasa de supervivencia a los 13 meses
? Tiempo hasta la muerte o la ventilación permanente en los subgrupos de sujetos por debajo de la mediana de la duración de la enfermedad en el estudio
? Tiempo hasta la muerte o la ventilación permanente en los subgrupos de sujetos por encima de la mediana de la duración de la enfermedad en el estudio |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
Justificación de los procedimientos simulados |
Sham-Procedure Controlled |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
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 |
Canada |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
|
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
|
LVLS |
Última visita Último paciente. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |