A Prospective, Long-Term Registry of Patients with a Diagnosis of Spinal Muscular Atrophy (SMA) - (RESTORE)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Effectiveness study (incl. comparative)

  Healthcare resource utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  OAV-101
• Medical condition to be studied:
  Spinal muscular atrophy

Population studied

• Short description of the study population:
  Inclusion Criteria: ; • Patients not treated with OAV-101 with a diagnosis of SMA genetically confirmed on or after 24-May-2018 ; OR ; Patients treated with OAV-101 with a genetically confirmed diagnosis of SMA regardless of ; the date of diagnosis. ; AND ; • Appropriate consent/assent has been obtained for participation in the registry. ; Exclusion Criteria: ; • Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat SMA.
• Age groups:
  • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
• Estimated number of subjects:
  700

Study design details

• Study design:
  Prospective, multi center, multinational, non-interventional observational registry of patients diagnosed with SMA.
• Main study objective:
  This registry will assess long-term outcomes of patients with a diagnosis of SMA. It will also characterize and assess long-term safety and effectiveness of OAV-101 in the real-world setting.
• Setting:
  Patients will be recruited from the following regions: ; o Australia/Asia Pacific ; o Europe ; o Middle East and Africa ; o Latin America ; o North America ; Centers may be identified from those participating in existing SMA registries including but not limited to the international SMA consortium (iSMAC), SMArtCARE, Cure SMA, French SMA Registry, CUIDAME (Spain) or may be recruited de novo by the RESTORE registry. Patients may be enrolled in either one of the existing SMA registries with their data transferred to this registry database or they may participate in this registry without being enrolled in an existing registry.
• Outcomes:
  To assess the effectiveness of treatments for SMA, characterize motor performance, assess the long-term safety of OAV-101, characterize risk of hepatotoxicity, thrombocytopenia, thrombotic microangiopathy, cardiac AEs and sensory abnormalities suggestive of ganglionopathy in SMA patients treated with OAV-101, assess ventilation-free survival and overall survival of all patients with SMA. To assess healthcare utilization, caregiver burden and patient functional independence. To characterize the natural history/epidemiology of patients with less than 4 copies of the SMN2 gene. To characterize the use of systemic glucocorticosteroids and other systemic immunosuppressive medication used to help manage the humoral immune response to the AAV9 vector.
• Data analysis plan:
  Data will be analyzed per the statistical analysis plan (SAP). The analysis populations will consist of all patients enrolled. The primary analysis will be to summarize outcomes by the therapy a patient was on at the time of enrollment. Descriptive statistics will be presented for the primary analysis. No formal a priori hypothesis testing will be performed. Continuous variables will be summarized using the number of observations, mean, 95% confidence interval (CI) for the mean, standard deviation (SD), standard error (SE), median, minimum, and maximum. Categorical data will be summarized using counts and percentages. Incidence rates (per person-years) and 95% CIs of AEs will be calculated. Survival will be presented using Kaplan-Meier methods. Further data analysis may be undertaken to meet specific regulatory requests.