A Prospective, Observational, Post-Authorisation Efficacy Study to Assess Long-term Effectiveness of Risdiplam in Patients with Genetically Confirmed 5q SMA

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  RISDIPLAM
• Medical condition to be studied:
  Spinal muscular atrophy

Population studied

• Age groups:
  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Renal impaired
• Estimated number of subjects:
  600

Study design details

• Main study objective:
  The primary objectives for this study are as follows: 1) To describe the real-world, long-term effectiveness of risdiplam on disease progression and to compare the impact of potential effect modifiers (symptomatic; status, SMN2 copy number) on long-term effectiveness, and 2) To compare the real-world, long-term effectiveness outcomes between a cohort of risdiplam-treated patients and a cohort of DMT-naive patients (untreated with; any DMT approved for SMA).
• Outcomes:
  Primary effectiveness outcomes: 1) Time to all-cause mortality (survival) by the end of study participation, 2) Time to prolonged/permanent ventilation, 3)Developmental motor milestone achievement, 4) Motor function assessed using Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), 5) Hammersmith Functional Motor Scale Expanded (HFMSE) or Revised Upper Limb Module (RULM). ; ; Secondary effectiveness outcomes: 1) Onset of symptoms (within the pre-symptomatic group), 2) Need for nutritional support/tube feeding, 3) Length of stay in hospitalisations and reasons for hospitalisations, 4) Withdrawal of risdiplam treatment and reasons for withdrawal of treatment (risdiplam cohort only). Tertiary effectiveness outcomes: 1) Motor function measure 32 (MFM32), 2( Revised Hammersmith Scale (RHS), 3) Timed function tests (e.g., 6-Minute Walk Test [6MWT], 10-Metre Walk Test [10MWT], Timed Up and Go [TUG] Test), 4) SMA Independence Scale (SMAIS).
• Data analysis plan:
  The raw data will be extracted from different data sources, followed by homogenization, pooling and then central analysis. All effectiveness outcomes will be summarized descriptively per cohort by an approximate 6-month timepoint. Continuous variables will be described with summary statistics such as n, mean, standard deviation, median, minimum, and maximum values. Also, treatment differences and 95% CIs will be presented. For each categorical variable, odds ratio, or relative risks, 95% CIs, frequency, and percentage will be reported. The time to event for each outcome will be reported in months, summarised descriptively and analysed using Kaplan-Meier method and Cox proportional hazards regression model. Median survival time estimates and survival probabilities at each study period time point will be analysed. The other objective will be achieved by comparing the two cohorts and using statistical techniques like inverse probability weighting and multivariable regression analysis.