An Observational Study on Sarilumab-exposed Pregnancies

Study Overview
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Brief Summary
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Primary Objective: To evaluate the relative risk of major structural birth defects, specifically a pattern of anomalies, in sarilumab-exposed pregnancies compared to disease-matched unexposed pregnancies. Secondary Objective: To evaluate the risk for sarilumab-exposure relative to the group of healthy pregnant women, and the effect of exposure on other adverse pregnancy and infants outcomes.

Detailed Description
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Pregnant women enrolled in the study will participate for the duration of that pregnancy. Those who deliver at least one live born infant and the infants will participate for 1 year after delivery of that infant.

Official Title
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Kevzara® (Sarilumab) Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

Conditions
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Rheumatoid Arthritis -Exposure During Pregnancy

Intervention / Treatment
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* Drug: Sarilumab SAR153191 (REGN88)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Cohort 1: Sarilumab-Exposed Cohort Currently pregnant, exposed to Kevzara (sarilumab) for approved indication Cohort 2: Disease-matched Comparison Cohort Currently pregnant, diagnosed with Kevzara (sarilumab) approved indication Cohort 3: Non-diseased Comparison Cohort Currently pregnant, not diagnosed with a Kevzara (sarilumab) indication and unexposed to Kevzara Exclusion criteria: First contact the Registry after prenatal diagnosis of any major structural defect or after pregnancy outcome is known (retrospective data). Enrolled in this cohort study with a previous pregnancy. Cohort 1: Sarilumab-Exposed Cohort Exposed to Kevzara (sarilumab) for an indication other than a currently approved indication. Exposure to another biologic during pregnancy or within 10 weeks prior to the first day of LMP. Exposed to methotrexate, cyclophosphamide, chlorambucil, or mycophenolate mofetil in pregnancy (ie, at any time after the LMP), or leflunomide within two years prior to pregnancy unless a blood level for leflunomide below 0.02 mcg/mL has been documented prior to LMP before the pregnancy. Cohort 2: Disease-matched Comparison Cohort Exposure to any Kevzara (sarilumab) during pregnancy or within 10 weeks prior to the first day of the LMP. Exposed to methotrexate, cyclophosphamide, chlorambucil, or mycophenolate mofetil in pregnancy (ie, at any time after the LMP), or leflunomide within two years prior to pregnancy unless a blood level for leflunomide below 0.02 mcg/mL has been documented prior to LMP before the pregnancy. Cohort 3: Non-diseased Comparison Cohort Diagnosed for any serious chronic disease that is thought to adversely impact pregnancy. Exposed to a known human teratogen during pregnancy as confirmed by the OTIS Research Center 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<br>Sarilumab-Exposed Cohort: Pregnant women exposed to Kevzara (sarilumab) for the treatment of an approved Kevzara (sarilumab) indication, for any number of days, at any dose, and at any time from the first day of the last menstrual period (LMP) up to and including the end of pregnancy | Drug: Sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:injection Route of administration: subcutaneous<br>* Other names: Kevzara;|
| Cohort 2<br>Disease-matched Comparison Cohort: Pregnant women diagnosed with Kevzara (sarilumab) approved indication. Approximate frequency matched to the exposed group by disease indication, validated by medical records, who have not been exposed to Kevzara (sarilumab) any time in the current pregnancy, and have taken another biologic DMARD medication for their disease within 2 years before the current pregnancy and have an indication for such treatment at enrollment | |
| Cohort 3<br>Non-diseased Comparison Cohort: Healthy pregnant women not diagnosed with a Kevzara (sarilumab) indication and unexposed to Kevzara (sarilumab) during the course of the pregnancy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major structural birth defect | A major structural birth defect is a defect that has either cosmetic or functional significance to the child (eg, a cleft lip) and is identified up to one year of age by the mother, the health care provider/medical record, or identified in the dysmorphological examination. | Up to 1 year of age of the infant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy Outcomes: Spontaneous abortion | Spontaneous abortion is defined as non-deliberate embryonic or fetal death that occurs < 20.0 weeks' gestation post-LMP (Last Menstrual period). | Date of conception to 20 weeks gestation | 
| Pregnancy Outcomes: Stillbirth | Stillbirth is defined as a non-deliberate fetal death that occurs at or after 20 weeks of gestation but prior to delivery. | After 20 weeks of gestation but prior to delivery | 
| Pregnancy Outcomes: Premature delivery | Premature delivery is defined as live birth prior to 37 weeks' gestation as counted from LMP (Last Menstrual period). | Live birth prior to 37 weeks gestation | 
| Infant Outcomes: pattern of minor structural birth defects | A specific pattern of 3 or more structural defects in live born infants with dysmorphological physical examination. | Up to 1 year of age of the infant | 
| Infant Outcomes: Small for gestational age | Proportion of infants less than or equal to the 10th percentile for sex and gestational age on weight, length, or head circumference. | At birth | 
| Infant Outcomes: 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 Outcomes: Serious or opportunistic infections | Proportion of infants who experienced serious or opportunistic infections up to 1 year of age. | Up to 1 year of age of the infant | 
| Infant Outcomes: Hospitalizations | Proportion of infants who experienced hospitalizations in the first year of life excluding those that are linked to premature delivery or birth defects included as endpoints. | Up to 1 year of age of the infant | 
| Infant Outcomes: Malignancies | Proportion of infants who reported malignancies reported in an infant after birth and up to 1 year of age. | Up to 1 year of age of the infant - |