E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal Muscular Atrophy (SMA) |
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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 |
To evaluate the long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to subjects with SMA who previously participated in investigational studies of nursinersen. |
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E.2.2 | Secondary objectives of the trial |
To examine the long-term efficacy of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to subjects with SMA who previously participated in investigational studies of nursinersen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria at Screening to be eligible:
1. Signed informed consent of parent or guardian and signed informed assent of subject, if indicated per subject’s age and institutional guidelines.
2. Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks. |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for the study:
1. Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
2. Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
3. Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
4. Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs) - Number of participants with clinically significant vital sign abnormalities - Number of participants with clinically significant weight abnormalities - Number of participants with clinically significant neurological examination abnormalities - Number of participants with clinically significant laboratory assessment abnormalities - Number of participants with clinically significant coagulation parameter abnormalities - Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities - Change from Baseline in concomitant medications |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria - Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) - Time to death or respiratory intervention - Percentage of participants not requiring permanent ventilation - Change from Baseline in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale - Change from Baseline in Hammersmith Functional Motor Scale - Change from Baseline in Revised Upper Limb Module (RULM) - Change from Baseline in 6-Minute Walk Test (6MWT) - Change from Baseline in Compound Muscular Action Potential (CMAP) - Change from Baseline in body length and/or height (for all participants) - Change from Baseline in head circumference (for participants up to 36 months of age) - Change from Baseline in chest circumference (for participants up to 36 months of age) - Change from Baseline in arm circumference (for participants up to 36 months of age) - Proportion of CMAP responders - Number of participants with motor milestones achieved - Proportion of participants who achieved standing alone - Proportion of participants who achieved walking with assistance - Number of participants with serious respiratory events - Number of participants hospitalized - Duration of hospitalizations - Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine - Change from Baseline in Quality of Life (QOL) Questionnaires - Number of Disease-related hospitalizations and AEs - Overall survival rate |
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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 | 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 | 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 |
The study is an open label extension |
|
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 | 14 |
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 |
Belgium |
Canada |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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 | 7 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |