The Eplontersen Pregnancy and Lactation Outcomes Study: A Descriptive Safety Study of Pregnant and Lactating Individuals and Their Offspring Exposed to Eplontersen (EPPRO)

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

Study drug and medical condition

• Name of medicine:
  WAINZUA
• Name of medicine, other:
  WAINZUA
• Anatomical Therapeutic Chemical (ATC) code:
  (N07XX21) eplontersen

  eplontersen
• Medical condition to be studied:
  Hereditary ATTR amyloid cardiomyopathy

  Pregnancy

Population studied

• Short description of the study population:
  The study population will include all pharmacovigilance reports of pregnant and/or lactating individuals diagnosed with an indication approved for use of eplontersen who administered at least one dose of eplontersen during pregnancy or lactation. Both prospectively and retrospectively reported cases will be included in the study population. ; Inclusion Criteria:; All pregnancy and/or lactation cases with exposure to eplontersen and a diagnosis of an; approved indication reported to the AZ PV database via clinical trials, spontaneous postmarketing; report sources, post-marketing observational studies, patient-oriented programs, published literature, and personal communication by HCPs are eligible for inclusion in the study. This is to; include:; 1. All notifiable pregnancy and lactation case reports in individuals exposed to; eplontersen and diagnosed with an approved indication for treatment with eplontersen ; 2. All AE reports in infants in the first 12 months of age that are or can be linked to; pregnancy or lactation reports in individuals previously diagnosed with an approved; indication and exposed to eplontersen during pregnancy or lactation ; This study will not include any eplontersen-unexposed pregnancies. ; Exclusion Criteria:; The following case reports to the AZ Global Safety Database via clinical trials, spontaneous; post-marketing report sources, post-marketing observational studies, patient-oriented; programs, published literature, and personal communication by HCPs will be excluded: ; 1. All case reports considered invalid (i.e., minimum data are not provided at first report; nor follow-up), or where reporter indicates that they do not wish to be contacted to; obtain follow-up information, or the reporter/patient cannot be identified;
• Age groups:
  • In utero
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
• Special population of interest:
  Nursing women

  Pregnant women
• Estimated number of subjects:
  10

Study design details

• Study design:
  This DPSS will analyze secondary data on cases of eplontersen-exposed pregnant and; lactating individuals collected through a PRegnancy outcomes Intensive Monitoring (PRIM); enhanced pharmacovigilance (PV) approach utilizing AstraZeneca’s PV Global Safety; Database (PV-Argus)
• Main study objective:
  The aim of this DPSS is to describe the occurrence of pregnancy and maternal complications; and adverse effects on the developing fetus, neonate, and infant among individuals exposed to; eplontersen during pregnancy and/or lactation. The incidence of each of the outcomes of; interest will be estimated among individuals exposed to at least one dose of eplontersen during; pregnancy; the incidence of infant outcomes will also be assessed among infants exposed to; eplontersen through breastmilk feeding.
• Setting:
  Exposed case collection with the PRIM approach is expected to begin in November; 2025 and will conclude in December 2035, i.e., data collection is planned for approximately; 10 years. For each exposed pregnancy, follow-up begins with the initial PV report and ends at; pregnancy outcome (if fetal loss) or at 12 months after pregnancy outcome (if live birth). For; instances where there is only lactation exposure, follow-up begins with the initial PV report; and ends 12 months after birth. In cases with ongoing exposure during breastfeeding at 8; months post-pregnancy or later, the follow-up period will be extended by an additional 15; weeks to EOP+470 days.
• Comparators:
  Not applicable
• Outcomes:
  • Composite outcome of all major congenital malformations (MCMs); • Composite outcome of all minor congenital malformations; • Molar or ectopic pregnancy; • Gestational diabetes; • Gestational hypertension, preeclampsia, eclampsia; • Placental disorder; • Fetal loss; o Spontaneous abortion (SAB); o Stillbirth; o Induced abortion; o Fetal loss, type not specified; • Live birth; • Preterm birth; • Small for gestational age (SGA); • Neonatal death; • Postnatal growth deficiency; • Infant developmental delay including assessment of social/emotional,; language/communication, cognitive (learning, thinking, problem-solving), and; movement/physical development); • Infant death;
• Data analysis plan:
  Analyses will be conducted in accordance with the study objectives, table/listing shells, and; applicable guidelines. Demographics, medical and obstetric history, and disease; characteristics will be summarized using descriptive statistics. The outcomes will be reported; as a proportion and 95% confidence interval (if applicable) and calculated by dividing the; number of cases of the outcome by the appropriate denominator for the particular outcome. If; fewer than ten cases are reported, formal analyses will not be performed, and reporting will be; limited to case narratives.
• Summary results:
  Not available yet