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

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Other

  Safety study (incl. comparative)
• If ‘other’, further details on the scope of the study:
  Safety and efficacy study of OAV-101 in the real-world setting

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Prospective, multi center, multinational, non-interventional observational registry of patients diagnosed with SMA.

Study drug and medical condition

• Medical condition to be studied:
  Spinal muscular atrophy

Population studied

• 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

• 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.
• 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.