Observational Cohort Study of Zavegepant Safety in Pregnancy within a US Claims Database

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Zavegepant

Population studied

• Short description of the study population:
  The base population will include all pregnancies among individuals with migraine with an EDC (estimated date of conception) between 09 March 2023 and 31 December 2030 (or most recent data available at the time of the last data extract) within the US-based health insurance claims database.
• Age groups:
  Paediatric Population (< 18 years)

  Adults (18 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  6188

Study design details

• Study design:
  This is an observational cohort study. Three cohorts of pregnancies among individuals with migraine; a cohort of zavegepant-exposed pregnancies and 2 propensity score-matched (1:3) comparator groups of pregnancies exposed to other migraine therapies and unexposed to migraine therapies.
• Main study objective:
  1. To estimate the prevalence of MCM births among pregnant individuals with migraine ; who are (1) exposed to zavegepant (exposed cohort), ; (2) unexposed to zavegepant (treated comparator cohort), ; and (3) unexposed to migraine treatment (untreated comparator cohort). ; ; 2. To estimate the relative risk of MCM births in the exposed cohort versus the comparator cohorts, if sample size permits.
• Setting:
  The base population will include all pregnancies among individuals with migraine with an EDC between 09 March 2023 and 31 December 2030 (or most recent data available at the time of the last data extract) within the US-based health insurance claims database.
• Comparators:
  The treated comparator cohort will include eligible pregnancies that meet the following criteria:; 1. Exposure period for a medication indicated for the acute treatment of migraine that overlaps with the relevant exposure window (Table 4). Exposure periods for migraine medications will be defined for each pregnancy using the date of dispensing or administration as the start of exposure, and the days' supply or recommended ; administration schedule plus 5 times the half-life of the therapy as the length of exposure. (a. Triptans and ditans).; 2. No exposure period for zavegepant that overlaps with the relevant exposure window; 3. Migraine, based on the criteria summarized in Table 3 (Identification of pregnancies with migraine in the present study); ; The untreated comparator cohort will include eligible pregnancies that meet the following criteria:; 1. No exposure periods for zavegepant, triptans, and ditans that overlap with an exposure window (defined as 30 days prior to EDC through the end of the relevant exposure window); 2. Migraine, based on the criteria summarized in Table 3
• Outcomes:
  The primary outcome is MCM. The secondary outcomes are spontaneous abortion, pregnancy complications (pre-eclampsia, eclampsia, gestational diabetes, gestational hypertension), stillbirth, preterm birth, and SGA. ;
• Data analysis plan:
  Annual interim reports will describe the flow of pregnancies into the 3 migraine cohorts including the number of accrued pregnancies meeting each of the eligibility criteria. Each study cohort will be described with respect to select covariates (Section 9.3.3). ; All analyses will be descriptive, including the number of observations, mean, standard deviation, median, interquartile range, and range for all continuous variables and counts and percentages for each binary or categorical variable. ; ; Claims-identified outcome counts will be provided to assess whether the prevalence estimates incorporated into the power calculation hold. These counts will include non-adjudicated MCM, as identified using the specific algorithm (Section 9.3.2).There will be no propensity score matching of the exposed to comparator group pregnancies in the annual interim reports and no comparative analyses. As noted in Section 9.4.4, the addition of research partners will be considered after the third annual interim report, based on observed accrual.; ; The comparative analysis in the final report will match exposed and comparator pregnancies on propensity scores to identify the final study cohorts.