Maternal and Postnatal Outcomes: A worldwide decentralized observational registry to evaluate the safety in women with Fabry disease and their infants after exposure to Elfabrio (pegunigalsidase alfa-iwxj/pegunigalsidase alfa) during pregnancy and/or lactation

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:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Case-only

  Cohort

Study drug and medical condition

• Medicinal product name:
  ELFABRIO
• Study drug International non-proprietary name (INN) or common name:
  PEGUNIGALSIDASE ALFA
• Anatomical Therapeutic Chemical (ATC) code:
  (A16AB20) pegunigalsidase alfa

  pegunigalsidase alfa
• Medical condition to be studied:
  Fabry's disease

Population studied

• Short description of the study population:
  The target population is all women with Fabry disease exposed to Elfabrio (pegunigalsidase alfa) during pregnancy and/or lactation and their fetuses, neonates and infants up to 12 months of age in the countries the study is launched in. ; ; As Fabry disease is a rare disease with X-linked inheritance, heterozygous female subjects show a variable expression with a broad range of disease severity, ranging from asymptomatic to classical phenotype, which in turn infuences timing of treatment initiation, often postponed compared with male patients. Moreover, there are currently different therapies approved for Fabry disease, including enzyme replacement treatments in the US and EU. Therefore, the number of pregnant women with Fabry disease treated with pegunigalsidase alfa cannot be accurately estimated. It is anticipated that very few pregnant women will be exposed to pegunigalsidase alfa every year; therefore a sample size of 10 women is expected for the duration of this study. ; ; Patients must meet all of the following inclusion criteria to be eligible for enrolment into the registry:; - Female patients with Fabry disease who have been exposed to at least 1 dose of pegunigalsidase alfa at any time during pregnancy (defined as having received pegunigalsidase alfa within 30 days prior to the date of conception [DOC] and/or during pregnancy) and/or during lactation. (DOC, defined as 2 0/7 gestational weeks, will be calculated from last menstrual period [LMP] or ultrasound); - Patient or parent/legally authorized representative must be able to understand and provide consent through an Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved Informed Consent Form (ICF).; ; There are no exclusion criteria.
• Age groups:
  • In utero
  • Neonate

    • Preterm newborn infants (0 – 27 days)
    • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Adults (18 to < 65 years)

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

  Pregnant women
• Special population of interest, other:
  Pediatric up to 12 months of age
• Estimated number of subjects:
  10

Study design details

• Study design:
  This is a worldwide, decentralized, single-arm, prospective and retrospective, observational registry study in women with Fabry disease exposed to pegunigalsidase alfa during pregnancy (within 30 days prior to DOC) and/or during pregnancy) and/or lactation, and their infants.;
• Main study objective:
  The objective of the registry is to evaluate pregnancy and clinical outcomes in women with Fabry disease and their infants after exposure to pegunigalsidase alfa at any time during pregnancy and/or lactation.
• Setting:
  Physicians of and women with Fabry disease residing in the countries the registry is launched in who are exposed to pegunigalsidase alfa during pregnancy (within 30 days prior to DOC) and/or during pregnancy) and/or lactation will be recruited to participate. ; ; Participation is decentralized and physicians and/or patients will participate in the registry and independently and remotely record patient's data through electronic case report forms (eCRFs) on the web-based platform. ; ; The registry is planned to enrol over a 10-year period. ; ; Pregnancy information will be collected until delivery or within 42 days of termination of pregnancy. Infant information will be collected up to 12 months of age. ;
• Comparators:
  Not applicable.
• Outcomes:
  Primary Outcome Measures:; 1. Pregnancy Outcome:; - Number of live births; - Number of preterm birth; - Number of pregnancy losses (spontaneous abortions, pregnancy terminations, fetal deaths or stillbirths); ; Secondary Outcome Measures:; - Number of neonates/infants with major congenital malformations (MCMs); - Number of ectopic or molar pregnancies; - Number of women with obstetric and delivery complications; - Number of women with complications of preeclampsia or eclampsia; - Number of women with complications of preterm prelabour rupture of membrane; - Number of neonates/infants with minor congenital malformations; - Number of infants with developmental deficiency; - Number of hospitalizations in infants; - Mortality in infants, including neonatal death and infant death; - Head circumference in infants; - Weight in infants; - Length in infants; - Number of infants born as small for gestational age (SGA); - Number of infants with postnatal growth deficiency or failure to thrive (FTT); - Duration of breastfeeding, number of exclusively breastfeeding women and number of breastfeeding women supplemented with formula; - Number of adverse events in infants exposed to pegunigalsidase alfa during breastfeeding
• Data analysis plan:
  Details about the planned statistical analysis will be described in the Statistical Analysis Plan (SAP) which will be finalized before database lock. ; ; Analyses will be descriptive, with data listings, frequency tabulations, and summary statistics as appropriate. No formal hypothesis testing will be performed. ; ; Descriptive statistics will comprise of the number of observations (n), mean, standard deviation (SD), median, minimum, and maximum for continuous variables, and n and percent for categorical variables. The 95% confidence intervals (CI) will also be presented for selected pregnancy outcomes. There will be no imputation for missing data. ; ; Demographic and other clinical characteristics will be summarized descriptively. ; ; Primary analyses:; The number and proportions with their 95% CI will be reported for each of the pregnancy outcomes including live births, preterm births, and pregnancy losses. ; ; Secondary analyses:; The number and proportion of patients/infants with the following birth and pregnancy outcomes will be calculated and reported. ; - Major and minor congenital malformations; - Ectopic or molar pregnancies; - Obstetric and delivery complications; - Preeclampsia or eclampsia; - Preterm prelabor rupture of membrane; - SGA; - Postnatal growth deficiency or FTT; - Infant developmental deficiency; ; The number and proportion of infant hospitalizations and infant mortality, including neonatal and infant death, will be reported. ; ; Infant head circumference, weight and length at birth and during follow-up will be summarized descriptively. ; ; Breastfeeding patterns will be summarized, including duration of breastfeeding, number of women exclusively breastfeeding and number of women who supplemented with formula. ; ; In addition, maternal deaths will be reported.