A Pregnancy Registry Study to Evaluate the Safety of PENBRAYA™ Meningococcal Vaccine Exposure During Pregnancy

Study type

• Study topic:
  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:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  PENBRAYA (meningococcal groups A, B, C, W and Y vaccine)
• Medical condition to be studied:
  Stillbirth
• Additional medical condition(s):
  Congenital malformation (MCM), spontaneous abortion(SAB), elective termination, preterm birth, and small for gestational age (SGA)

Population studied

• Short description of the study population:
  The study population will include a single cohort of pregnant individuals in the US exposed to PRENBAYA during pregnancy.
• 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)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  50

Study design details

• Study design:
  This registry-based, prospective, observational cohort study will enroll and follow pregnant individuals 10-25 years of age in the US who are exposed to PENBRAYA during pregnancy. Data will be collected from enrolled pregnant individuals and the healthcare providers (HCPs) involved in their care.
• Main study objective:
  To estimate the proportion of major congenital malformation (MCM), spontaneous abortion (SAB), elective termination, stillbirth, preterm birth, and small for gestational age (SGA) among individuals exposed to PENBRAYA during pregnancy or within 30 days prior to last menstrual period (LMP).
• Setting:
  The study population will be derived from eligible individuals in the US enrolled in the pregnancy registry. The virtual registry coordinating center (VRCC) will coordinate enrollment and data collection. Pregnant individuals will be; identified in the US during the study period using an active, targeted, multi-pronged recruitment campaign.
• Outcomes:
  Outcomes of interest: major congenital malformation (MCM), spontaneous abortion (SAB), elective termination, stillbirth, preterm birth, and small for gestational age (SGA). For outcomes not reported by the HCP, additional information on outcome ascertainment is provided.
• Data analysis plan:
  Demographic and baseline characteristics will be summarized with descriptive statistics for the study population.; ; The number of observations, median, mean, standard deviation, minimum, and maximum will be reported for each continuous variable. The frequency and percentage per category will be reported for each categorical variable. Proportion of the outcomes of interest will be calculated according to the conventions described in protocol Table 4. In general, the proportion of each outcome will be calculated by dividing the number of cases of the outcome by the appropriate denominator for that particular outcome, based on clinical knowledge. For most outcomes, the analysis population (denominator) will be the number of pregnant individuals with pregnancy outcome data, the number of live births, or the number of infants with follow-up data at the timepoint of interest, as appropriate; however, for some outcomes, the analysis population (denominator) will be restricted based on certain relevant factors (as noted in Table 4). If sample size permits, subgroup analyses will be conducted that consider timing of exposure (earliest trimester of exposure), extent of exposure (cumulative vaccine doses during pregnancy, or relevant exposure window), and maternal age group at conception (10 to <18, 18 to 25 years). Supplementary analyses will be conducted that include pregnant individuals who were excluded from the analysis population due to occurrence of the pregnancy outcome prior to enrollment (retrospectively enrolled participants) or exposure to a known teratogen or an investigational medication during or prior to pregnancy (teratogen/investigational medication-exposed participants). Sensitivity analyses of major congenital malformation that applies a stricter definition of prospective enrollment and that restricts the preconception exposure window to 28 days prior to conception rather than 30 days prior to last menstrual period will also be conducted.