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

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

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

Study drug and medical condition

• Medicinal product name:
  KOSELUGO
• Study drug International non-proprietary name (INN) or common name:
  SELUMETINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01EE04) selumetinib

  selumetinib
• Medical condition to be studied:
  Neurofibromatosis

Population studied

• Short description of the study population:
  The target population for this study are patients with NF1 in the EU with symptomatic, ; inoperable PN who have been prescribed at least 1 dose of selumetinib and who are aged ; 3 to < 18 years at the start of selumetinib treatment, except for those patients receiving ; treatment with a mitogen-activated protein kinase inhibitor before the index date.; ; The study will enrol 2 cohorts:; 1 The Base Cohort includes all enrolled patients aged 3 to <18 years.; 2 The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 ; to <18 years who have not reached Tanner Stage V on the index date.
• 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).
• Setting:
  This study will be conducted in up to 52 specialist clinics for the treatment of paediatric patients with NF1 across up to 12 European countries and Israel. The study observation period was anticipated to begin in Q2 of 2022, with some variation by country (actual start date was 23 May 2022). Patients will be enrolled after selumetinib access ; is commercially available and patients are able to receive the medicine as part of local clinical practice. To meet study timelines and minimise any delay in delivering the study results, countries where selumetinib is first available will be selected for the study.
• 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.