Evaluation of pregnancy and infant outcomes in Mayzent patients using PRegnancy outcomes Intensive Monitoring (PRIM) data – The Mayzent-PRIM study

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  SIPONIMOD
• Medical condition to be studied:
  Multiple sclerosis

  Pregnancy

  Congenital anomaly

  Foetal malformation

  Stillbirth

  Abortion spontaneous

  Exposure during pregnancy

  Drug exposure before pregnancy

Population studied

• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  500

Study design details

• Main study objective:
  To estimate the proportion of major congenital malformations associated with exposure to siponimod immediately before (up to 10 days before LMP) and during pregnancy among (i) live births and (ii) live births, stillbirths, and termination of pregnancy for fetal anomaly (TOPFA).
• Outcomes:
  Major congenital malformation, To estimate the proportion of minor malformations, pregnancy outcomes, overall malformations, physical and cognitive development and serious infections in infants up to one year of age
• Data analysis plan:
  A statistical analysis plan (SAP) detailing the analysis to be conducted will be developed prior to the first data lock point. Annual interim reports will be provided as described in the Milestones section below. The primary Mayzent-PRIM analysis cohort will constitute of the prospectively reported pregnancies associated with maternal exposure during pregnancy or up to 10 days before LMP. Since retrospective cases may be subject to reporting biases but still be informative, these will be analyzed and reported separately. Note that comparison with external background data will only be performed for the primary cohort, due to the high risk of bias for retrospective reports. Data analysis will include the estimation of proportion and 95% confidence intervals (CI) of malformations and specific pregnancy and infant outcomes. The proportion of congenital malformations will be calculated amongst (i) live births, and (ii) live births, stillbirths, and TOPFA.