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 |
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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 | 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 assess long-term safety in terms of treatment-emergent serious adverse events (SAEs) and treatment-emergent adverse events of special interest (AESIs)
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are; (1) assess long-term efficacy of OAV101 treatment. (2) assess long-term safety for measures other than adverse events . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants eligible for inclusion in this study must meet all of the following criteria: 1. Received OAV101 IT or OAV101 IV in a Phase I to IIIb clinical trial sponsored by AveXis, Novartis or Novartis Gene Therapies. 2. Patient/Parent/legal guardian willing and able to complete the informed consent process and comply with study procedures.
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E.4 | Principal exclusion criteria |
Score “yes” on item 4 or item 5 of the suicidal ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or “yes” on any item of the suicidal behavior section, except for the “Non-Suicidal Self-Injurious Behavior” (item also included in the suicidal behavior section) if this behavior occurred in the past 2 years. |
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E.5 End points |
E.5.1 | Primary end point(s) |
● Number of participants with treatment-emergent serious adverse events (SAEs) by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and Preferred Term (PT) for the entire duration of the study (i.e., up to 15 years) ● Number of participants with treatment-emergent adverse events of special interest (AESIs) by AESI category and MedDRA SOC and PT within each AESI category for the entire duration of the study (i.e., up to 15 years)
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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) |
● The number and proportion of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist ● The number and proportion of participants demonstrating maintenance of each developmental milestone ● Change from Baseline in the Hammersmith Functional Motor Scale – Expanded (HFMSE) total score ● Change from Baseline in the Revised Upper Limb Module (RULM) total score ● Proportion of patients with potentially clinically significant vital sign findings, summarized individually for each vital sign parameter ● Proportion of patients with potentially clinically significant laboratory values, summarized individually for each laboratory parameter
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Exploratory ● To explore other potential effects of OAV101 on exploratory efficacy and safety biomarkers ● To assess long-term safety in terms of adverse events ● To describe the time-course of the elevation of anti-AAV9 antibodies after administration of OAV101 ● To assess long-term Caregiver experience
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Long-term follow-up of patients with SMA Treated with OAV101 IT or IV administration. No study drug. |
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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 | 21 |
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 |
China |
Colombia |
Egypt |
India |
Japan |
Malaysia |
Mexico |
Saudi Arabia |
Singapore |
South Africa |
Taiwan |
Thailand |
United States |
Viet Nam |
France |
Netherlands |
Spain |
Switzerland |
Germany |
Italy |
Belgium |
Denmark |
Portugal |
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
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The end of the LTFU study for each individual Spinal Muscular Atrophy (SMA) patient will be 15 years after treated with OAV101 by intravenous (IV) or intrathecal (IT) administration received from a parent trial. The end of study as a whole is defined as the last patient's last visit (LPLV), which is the last patient's last evaluation (visit Year 15), or the time of premature withdrawal. |
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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 | 16 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 17 |
E.8.9.2 | In all countries concerned by the trial months | 5 |