E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Spinal Muscular Atrophy (SMA) |
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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 |
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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 |
The primary objective of this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol. |
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E.4 | Principal exclusion criteria |
- Treatment with another investigational therapy or enrollment in another interventional clinical study after the Day 302 visit in study 232SM203 (NCT04089566).
- Treatment with Zolgensma (all participants) after the Day 302 visit of study 232SM203 (NCT04089566). - Treatment with an approved therapy for SMA (other than Zolgensma) that is inconsistent with protocol requirements for allowed or disallowed concomitant therapies
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
2) Change from Baseline in Growth Parameters
3) Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
4) Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
5) Number of Participants With Shifts from Baseline in Vital Signs
6) Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
7) Change from Baseline in Prothrombin Time (PT)
8) Change from Baseline in International Normalized Ratio (INR)
9) Change from Baseline in Urine Total Protein
10) Change from Baseline in Neurological Examination Outcomes for Participants </= 2years of age
11) Change from Baseline in Neurological Examination Outcomes for Participants > 2 years of age
12) Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
13) Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia’s Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For Primary endpoints 1) , 2), 3), 4), 5), 9), 10), 11), 12), 13)
Up to Day 1081
For Primary endpoints 6), 7), 8)
Up to Day 961 |
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E.5.2 | Secondary end point(s) |
1) Total Number of New World Health Organization (WHO) Motor Milestones
2) Number of Participants Who Used Respiratory Support, by Type
3) Number of Hours Per Day of Respiratory Support
4) Number of Days That Respiratory Support Is Used
5) Time to Death (Overall Survival)
6) Change from Baseline in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
7) Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
8) Percentage of HINE Section 2 Motor Milestone Responders
9) Percentage of Time Spent on Ventilation
10) Time to Death or Permanent Ventilation
11) Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
12) Change from Baseline in Revised Upper Limb Module (RULM) Score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.3 |
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 | 24 |
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 |
Canada |
Chile |
Colombia |
Israel |
Korea, Republic of |
Lebanon |
Mexico |
Russian Federation |
Saudi Arabia |
Taiwan |
Turkey |
United States |
Estonia |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Latvia |
Poland |
Spain |
Argentina |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 11 |