Evolocumab Pregnancy Exposure Registry

Evolocumab Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

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

Study Overview

• Status: Terminated
• Conditions: Hypercholesterolemia; ASCVD; Pregnancy
• Intervention / Treatment: Drug: evolocumab

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 140

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women diagnosed with ASCVD or hypercholesterolemia associated with FH and pregnant women who have been exposed to Evolocumab (Repatha) during pregnancy and who reside in the U.S. or Canada

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Specific Evolocumab-Exposed Cohort; Women diagnosed with Atherosclerotic Cardiovascular Disease (ASCVD), or hypercholesterolemia associated with Familial Hypercholesterolemia (FH), who were exposed to Evolocumab (Repatha) during pregnancy	Drug: evolocumab; Pregnant women exposed to evolocumab. Evolocumab is not administered in this non-interventional study.; Other Names: Repatha
Comparison Group I; 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; 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; Women who were exposed to Evolocumab (Repatha) but do not fulfill eligibility criteria for the Specific Evolocumab-Exposed Cohort	Drug: evolocumab; Pregnant women exposed to evolocumab. Evolocumab is not administered in this non-interventional study.; Other Names: Repatha

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Organization of Teratology Information Specialists (OTIS) Research Center - tel: 1-866-626-6847 or www.mothertobaby.org

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): September 2, 2020
• Study Completion (Actual): September 2, 2020

Study Registration Dates

• First Submitted: October 26, 2016
• First Submitted That Met QC Criteria: November 3, 2016
• First Posted (Estimate): November 8, 2016

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Pregnancy; Cardiovascular Diseases; High serum cholesterol; FH; ASCVD
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 20150338

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)