E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscular Atrophy, Spinal |
Atrofia muscular espinal |
|
E.1.1.1 | Medical condition in easily understood language |
Spinal Muscular Atrophy (SMA) |
Atrofia muscular espinal (AME) |
|
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 | 20.1 |
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 |
The primary objective of this study is to evaluate the clinical outcomes following treatment with nusinersen in participants with spinal muscular atrophy (SMA) who previously received onasemnogene abeparvovec. |
El objetivo principal de este estudio es Evaluar los resultados clínicos tras el tratamiento con nusinersén en participantes con AME que recibieron previamente onasemnogene abeparvovec |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the safety and tolerability; and clinical outcomes following treatment with nusinersen in participants with SMA who previously received onasemnogene abeparvovec. |
Los objetivos secundarios de este estudio son evaluar la seguridad y tolerabilidad; y resultados clínicos tras el tratamiento con nusinersen en participantes con AME que recibieron previamente onasemnogene abeparvovec. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote). - Must have previously received onasemnogene abeparvovec. - Participants with suboptimal clinical status per the Investigator.
Note: other protocol defined Inclusion/Exclusion criteria may apply. |
- Documentación genética de 5q SMA (deleción, mutación o heterocigoto compuesto de genes homocigotos). - Debe haber recibido previamente onasemnogene abeparvovec. - Participantes con estado clínico subóptimo según el investigador.
Nota: pueden aplicarse otros criterios de inclusión / exclusión definidos por el protocolo. |
|
E.4 | Principal exclusion criteria |
- Prior exposure to nusinersen. - Ongoing severe or serious AEs related to onasemnogene abeparvovec. - Use of steroids within 1 month prior to first dose of nusinersen.
Note: other protocol defined Inclusion/Exclusion criteria may apply. |
- Exposición previa a nusinersen. - AA severos o graves en curso relacionados con el onasemnogene abeparvovec. - Uso de esteroides durante el mes anterior a la primera dosis de nusinersen.
Nota: pueden aplicarse otros criterios de inclusión / exclusión definidos por protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Total Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones Score |
Examen neurológico infantil de Hammersmith (HINE) Puntuación total de hitos motores de la sección 2 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to Day 778 |
Hasta el día 778 |
|
E.5.2 | Secondary end point(s) |
1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
2) Number of Participants with Change from Baseline in Clinical Laboratory Parameters
3) Number of Participants with Change from Baseline in Electrocardiograms (ECGs)
4) Number of Participants with Change from Baseline in Vital Signs
5) Number of Participants who Achieved Motor Milestones as Assessed by World Health Organization (WHO) Criteria
6) Change from Baseline in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Score
7) Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
8) Change from Baseline in Revised Upper Limb Module (RULM) Score
9) Time to Death or Permanent Ventilation |
1) Número de participantes con eventos adversos (EA) y eventos adversos graves (SAE)
2) Número de participantes con cambios con respecto al valor inicial de los parámetros de laboratorio clínico
3) Número de participantes con cambios con respecto al valor inicial en los electrocardiogramas (ECG)
4) Número de participantes con cambios con respecto al valor inicial en los signos vitales
5) Número de participantes que lograron hitos motores según la evaluación de los criterios de la Organización Mundial de la Salud (OMS)
6) Cambio con respecto al valor inicial en la puntuación de la prueba infantil de trastornos neuromusculares del Children's Hospital of Philadelphia (CHOP INTEND)
7) Cambio con respecto al valor inicial en la escala motora funcional de Hammersmith: puntuación ampliada (HFMSE)
8) Cambio con respecto al valor inicial en la puntuación revisada del módulo de miembros superiores (RULM)
9) Tiempo hasta la muerte o ventilación permanente |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to Day 778 |
Hasta el día 778 |
|
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Israel |
United States |
Germany |
Italy |
Spain |
|
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
|
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |