Praluent® (Alirocumab) Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

Study Overview
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Brief Summary
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Primary Objective: To estimate the overall combined rate of major structural birth defects in infants of mothers with atherosclerotic cardiovascular disease (ASCVD) and/or familial hypercholesterolemia (FH) exposed to Praluent® (alirocumab) during pregnancy when used to treat hypercholesterolemia and to compare that rate to unexposed disease-matched and unexposed non-diseased comparison pregnancies. Secondary Objectives: Secondary objectives are to estimate the rates of the outcomes in pregnancies/infants of mothers with atherosclerotic cardiovascular disease and/or familial hypercholesterolemia exposed to alirocumab during pregnancy when used to treat hypercholesterolemia and to compare that rate to unexposed disease-matched and non-diseased comparison pregnancies, and secondarily to compare the rates of these outcomes in the unexposed disease-matched pregnancies to the rates in the unexposed non-diseased comparison pregnancies. Safety and tolerability of alirocumab.

Official Title
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Praluent® (Alirocumab) Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: ALIROCUMAB SAR236553 (REGN727)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Cohort 1: Alirocumab-Exposed: Currently pregnant - Diagnosed with primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia - Exposed to alirocumab for any number of days, at any dose, and at any time from the first day of the last menstrual period up to and including the end of pregnancy - Agree to the conditions and requirements of the study and provide informed consent. Cohort 2: Disease-Matched Comparison: Currently pregnant - Diagnosed with primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia - Unexposed to alirocumab or any biologic medication during pregnancy or any time within 10 weeks prior to the first day of the last menstrual period - Agree to the conditions and requirements of the study and provide informed consent. Cohort 3: Non-Diseased Comparison: Currently pregnant - Not diagnosed with primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia - Unexposed to alirocumab or any biologic any time in pregnancy or within 10 weeks prior to the first day of the last menstrual period - Unexposed to any known human teratogens as determined by the Organization of Teratology Information Specialists Research Center - Agree to the conditions and requirements of the study and provide informed consent. Exclusion criteria: Cohort 1: Alirocumab-Exposed: First contact the Registry after prenatal diagnosis of a major structural birth defect - Enrollment in this pregnancy registry study with a previous pregnancy - Pregnancy outcome is reported retrospectively. Cohort 2: Disease-Matched Comparison: First contact the Registry after prenatal diagnosis of a major structural birth defect - Exposure to any alirocumab or other biologic medication during pregnancy or within 10 weeks prior to the first day of the last menstrual period - Enrollment in this pregnancy registry study with a previous pregnancy - Pregnancy outcome is reported retrospectively. Cohort 3: Non-Diseased Comparison: First contact the Registry after prenatal diagnosis of a major structural birth defect - Exposure to alirocumab or other biologic medication during pregnancy or within 10 weeks prior to the first day of the last menstrual period - Exposure to a known human teratogen as determined by the Organization of Teratology Information Specialists Research Center - Enrollment in this pregnancy registry study with a previous pregnancy - Pregnancy outcome is reported retrospectively. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1 : alirocumab exposed<br>Pregnant women diagnosed with primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia and exposed to alirocumab during the current pregnancy. | Drug: ALIROCUMAB SAR236553 (REGN727)<br>* Pharmaceutical form:as per routine practice Route of administration: subcutaneous<br>* Other names: Praluent®;|
| Cohort 2 : disease matched comparison<br>Pregnant women diagnosed of primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia and unexposed to alirocumab during the current pregnancy. | |
| Cohort 3 : non disease comparison<br>Healthy pregnant women who do not have a known diagnosis of primary hypercholesterolemia and atherosclerotic cardiovascular disease, or primary hypercholesterolemia associated with familial hypercholesterolemia and have no known exposure to a known human teratogen. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major structural birth defects | Overall combined rate of major structural birth defects in infants born to females with atherosclerotic cardiovascular disease (ASCVD) and/or familial hypercholesterolemia (FH) exposed to Praluent (alirocumab) | Up to 1 year of age of the infant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy outcome: Spontaneous abortion | Rate of spontaneous abortion | Date of conception to 20 weeks gestation | 
| Pregnancy outcome: Elective abortion | Rate of elective abortion | Date of conception to 20 weeks gestation | 
| Pregnancy outcome: Still birth | Rate of still birth | At birth | 
| Pregnancy outcome: Preterm delivery | Rate of preterm delivery | Live birth prior to 37 weeks gestation | 
| Infant outcome: Pattern of minor structural birth defects | Specific pattern of 3 or more minor structural defects in live born infants receiving the exam | Up to 1 year of age of the infant | 
| Infant outcome: Small for gestational age | Proportion of infants who are small for gestational age on weight, length, or head circumference | At birth | 
| Infant outcome: Postnatal growth deficiency | Proportion of infants less than or equal to the 10th percentile for sex and age on weight, length, or head circumference at 1 year postnatal evaluation | Up to 1 year of age of the infant | 
| Infant outcome: serious infections or hospitalizations, adverse reactions to childhood vaccinations | Proportion of infants who experienced serious infections or hospitalizations, and adverse reactions to childhood vaccinations | Up to 5 years of age of the child | 
| Infant outcome: adequacy of immune response | Proportion of infants who has adequate immune response as measured by IgG-Tetanus antibody | Up to 5 years of age of the child | 
| Infant outcome: adverse neurodevelopment | Proportion of infants who experienced adverse neurodevelopment | Up to 5 years of age of the child | 
| Breastfeeding/Lactation outcome | Proportion of patients breastfeeding in the first 6 weeks after delivery | Up to 6 weeks of age of the infant | 
| Breastfeeding/Lactation outcome | Proportion of patients breastfeeding exclusively for more than 2 weeks | Up to 2 years of age of the child | 
| Adverse events | Proportion of patients who experienced adverse events (AEs), AEs of special interest, and serious AEs | Up to 5 years follow-up period |