Evolocumab Pregnancy Exposure Registry

Study Overview
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Brief Summary
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This is a prospective observational registry study to evaluate fetal, infant and childhood outcomes in women exposed to evolocumab during pregnancy

Detailed Description
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This pregnancy registry will be conducted by University of California Research Center for the Organization of Teratology Information Specialists (OTIS) which is a network of university and health department based telephone information centers serving pregnant women and healthcare providers throughout North America. Participants will be enrolled on an ongoing basis through year 10 of the study and each will be followed from the time they enroll, through the 5-year postnatal follow up period for an overall study period of 15 years. Participants are recruited concurrently from callers to OTIS centers, from healthcare providers and through direct to consumer marketing efforts.

Official Title
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Evolocumab Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

Conditions
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Hypercholesterolemia; ASCVD; Pregnancy

Intervention / Treatment
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* Drug: evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all groups: Qualified subjects will agree to the conditions and requirements of the study including the interview schedule, release of medical records, the physical examination of live born infants, and 5 years of follow-up. For the Specific Evolocumab-Exposed Cohort: Currently pregnant women (maternal report validated by medical records) diagnosed with ASCVD, or hypercholesterolemia associated with FH who have been exposed to evolocumab for any number of days, at any dose, and at any time from the first day of the LMP up to and including the end of pregnancy. For Comparison Group I: Currently pregnant women (maternal report validated by medical records) diagnosed with ASCVD, or hypercholesterolemia associated with FH but who were not exposed to evolocumab during pregnancy or any time within 90 days prior to the first day of the LMP. For Comparison Group II: Currently pregnant women not diagnosed with ASCVD, or hypercholesterolemia associated with FH who have not been exposed to evolocumab during pregnancy or any time within 90 days prior to the first day of the LMP, and who have no exposure to any known human teratogens as determined by the OTIS Research Center For General Evolocumab-Exposed Case Series group: Women with exposure to evolocumab during pregnancy who do not meet the criteria for the Specific Evolocumab-Exposed cohort for reasons including (but not limited to): they do not have ASCVD and/or hypercholesterolemia associated with FH (off-label use), they were exposed to evolocumab but the pregnancy has already completed, they enrolled in the cohort study with a previous pregnancy, or they already have a prenatal diagnosis of a major birth defect Exclusion Criteria: For all groups except the General Evolocumab Exposed Case Series Group: Women who first contact the Registry after prenatal diagnosis of a major structural defect Women who were exposed to a different PCSK9 inhibitor during their current pregnancy or at any time within 5 half-lives prior to the first day of the LMP Women who have enrolled in this Registry with a previous pregnancy

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Specific Evolocumab-Exposed Cohort<br>Women diagnosed with Atherosclerotic Cardiovascular Disease (ASCVD), or hypercholesterolemia associated with Familial Hypercholesterolemia (FH), who were exposed to Evolocumab (Repatha) during pregnancy | Drug: evolocumab<br>* Pregnant women exposed to evolocumab. Evolocumab is not administered in this non-interventional study.<br>* Other names: Repatha;|
| Comparison Group I<br>Women diagnosed with Atherosclerotic Cardiovascular Disease (ASCVD), or hypercholesterolemia associated with Familial Hypercholesterolemia (FH) who were not exposed to Evolocumab during pregnancy | |
| Comparison Group II<br>A general comparison group of pregnant women who have not been diagnosed with Atherosclerotic Cardiovascular Disease (ASCVD), or hypercholesterolemia associated with Familial Hypercholesterolemia (FH), and who were not exposed to Evolocumab during pregnancy. | |
| General Evolocumab-Exposed Case Series<br>Women who were exposed to Evolocumab (Repatha) but do not fulfill eligibility criteria for the Specific Evolocumab-Exposed Cohort | Drug: evolocumab<br>* Pregnant women exposed to evolocumab. Evolocumab is not administered in this non-interventional study.<br>* Other names: Repatha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major structural defects | Rate of major structural defects, defined and classified by the Centers for Disease Control and Prevention (CDC) Metropolitan Atlanta Congenital Defects Program (MACDP) 6 Digit Code Defects List coding manual (CDC, 2007) | Up to 1 year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy Outcome: Rate of spontaneous abortion | Rate of spontaneous abortion where spontaneous abortion is defined as non-deliberate fetal death which occurs prior to 19 completed weeks post-last menstrual period (LMP) | Up to 19 wks post LMP | 
| Pregnancy Outcome: Rate of elective abortion | Rate of elective abortion where elective abortion is defined as deliberate termination of pregnancy at any time in gestation | Through 9 month pregnancy period | 
| Pregnancy Outcome: Rate of stillbirth | Rate of stillbirth where stillbirth is defined as non-deliberate fetal death anytime in gestation at or after 19 completed weeks post-LMP | At or after 19 completed weeks post LMP | 
| Pregnancy Outcome: Rate of premature delivery | Rate of premature delivery where premature delivery is defined as live birth prior to 37.0 weeks gestation as counted from LMP (or ultrasound adjusted date) | Prior to 37 weeks of gestation | 
| Infant Outcome: Rate of minor structural defects | Rate of minor structural defects where a minor structural defect is defined as a structural anomaly which has neither cosmetic nor functional significance to the child. | Between birth and 12 months post natal | 
| Infant Outcome: Rate of small for gestational age | Rate of small for gestational age where small for gestational age is defined as birth size (weight, length, or head circumference) less than/equal to the 10th centile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants | At birth | 
| Infant Outcome: Rate of postnatal growth deficiency | Rate of postnatal growth deficiency where postnatal growth deficiency is defined as postnatal size (weight, length, or head circumference) less than/equal to the 10th centile for sex and age using standard pediatric growth curves, and adjusted for postnatal age for premature infants if the postnatal measurement is obtained at less than 1 year of age. | Up to 1 year of age | 
| Infant Outcome: Rate of postnatal hospitalizations | Rate of postnatal hospitalizations as assessed throughout the 5-year postnatal follow-up period. | Through 5 years postnatal | 
| Infant Outcome: Rate of infant reactions to scheduled vaccinations | Rate of infant reactions to scheduled vaccinations as assessed throughout the 5-year postnatal follow-up period. | Through 5 years postnatal | 
| Infant Outcome: Infant response to IgG-tetanus antibody | Infant response to IgG-tetanus antibody as a biological marker to evaluate humoral immune response via a standardized assay test. | Between 6-12 months of age | 
| Infant Outcome: Adverse neurodevelopment outcomes | Adverse neurodevelopmental outcomes as assessed during 2 periods (between 16 months to 17 months 30 days of age and between 3.5-5 years of age) via standardized tests of performance | Between 16 months to 17 months 30 days of age and between 3.5-5 years of age | 
| Breastfeeding/Lactation Outcome: Proportion of women who breastfed | Proportion of women who breastfed (at all) in the first 6 weeks after delivery | Through 6 weeks post delivery | 
| Breastfeeding/Lactation Outcome: Proportion who breastfed exclusively | Among women who breastfed (in the first 6 weeks after delivery), the proportion who breastfed exclusively during the first 2 weeks of life | Through the first 2 weeks postnatal | 
| Infant Outcome: Pattern of minor structural defects | Pattern of minor structural defects where a minor structural defect is defined as a structural anomaly which has neither cosmetic nor functional significance to the child and a pattern is defined as the same 3 or more minor structural defects in 2 or more children. | Between birth and 12 months postnatal | 
| Infant Outcome: Rate of postnatal serious infections | Rate of postnatal serious infections as assessed throughout the 5-year postnatal follow-up period. | Through 5 years postnatal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy; Cardiovascular Diseases; High serum cholesterol; FH; ASCVD