Patisiran-LNP Pregnancy Surveillance Program

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Pregnancy exposure surveillance

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Pregnancy exposure surveillance program

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PATISIRAN
• Medical condition to be studied:
  Hereditary neuropathic amyloidosis

  Familial amyloidosis

  Amyloidosis

  Cardiac amyloidosis

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:
  10

Study design details

• Main study objective:
  To estimate the frequency of selected fetal/neonatal/infant outcomes at birth and through the first year of life of infants from pregnancies in women exposed to patisiran-LNP.
• Outcomes:
  Prevalence of major congenital malformations. Prevalence of minor congenital malformations, pregnancy outcomes (live birth, spontaneous abortions, stillbirths, elective abortions, molar or pregnancy, ectopic pregnancy, preterm births, and maternal death) and other adverse fetal/neonatal/infant outcomes (low birth weight, failure to thrive, small for gestational age, postnatal growth and development, neonatal, and perinatal, or infant death).
• Data analysis plan:
  Descriptive statistics will be used to summarize the findings. The prevalence of all outcomes will be calculated per 100 pregnancies or births, as appropriate, along with 95% CI. Exact 95% CIs including Clopper-Pearson CI for binomial proportion will be presented. The prevalence of congenital malformations will be calculated using Metropolitan Atlanta Congenital Defects Program (MACDP) and European Concerted Action on Congenital Anomalies and Twins (EUROCAT) conventions. Prevalence of congenital malformations and spontaneous abortions will be estimated based on first trimester exposure to patisiran-LNP. If too few patients are enrolled to perform the analyses described above, a case series analysis may be performed. If sample size is sufficiently large, exploratory analyses will be conducted to study the effects of the timing of patisiran-LNP exposure before and during pregnancy and cumulative exposure periods on each outcome.