Post-Authorisation Safety Study of Paediatric Patients Initiating Selumetinib: A Multiple-Country Prospective Cohort Study

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Prospective cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  SELUMETINIB
• Medical condition to be studied:
  Neurofibromatosis

Population studied

• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Estimated number of subjects:
  125

Study design details

• Main study objective:
  To characterise the safety of selumetinib, including up to 5 years of long-term safety, in paediatric patients with NF1-related symptomatic, inoperable PN, 8 to < 18 years old who have not reached Tanner Stage V at the start of selumetinib treatment (Nested Prospective Cohort).
• Outcomes:
  1. LVEF reduction 2. Physeal dysplasia 3. Rise of serum creatine phosphokinase levels AND concurrent musculoskeletal symptoms 4. Rise in transaminase (ALT and AST) and concurrent rise in bilirubin 5. Abnormalities of ophthalmological examination (eg, vision changes, IOP, etc) 6. Abnormal pubertal development, 1. Demographics: Age, sex, height, weight, Tanner staging level, and ethnicity (where allowed by GDRP/privacy laws) 2. Clinical characteristics: PN(s) (number, location, classification and morbidities), prior medication and relevant procedures, concomitant medications, comorbidities, date of initial NF1 and PN diagnosis, NF1 origin (familial or spontaneous), and any genetic testing results.
• Data analysis plan:
  Tabular summaries will be provided for the baseline characteristics of the Base Cohort. Demographic and clinical characteristics data obtained at baseline will be summarised using descriptive statistics: mean, standard deviation, median, minimum and maximum for continuous variables and number and percentages for categorical variables. Safety outcomes of interest will be summarised at each follow-up visit. For each outcome cumulative incidence and incidence rate with 2-sided 95% exact confidence interval will be provided. Descriptive summary statistics will be obtained for duration of exposure to selumetinib, cumulative exposure to selumetinib, and number of dose reductions, discontinuations, or interruptions. The frequency of missing values for each variable will be examined and evaluated to determine whether data are missing at random in the data source.