Post-authorization Safety Study in North America to Monitor Pregnancy and Infant Outcomes Following Administration of Dupilumab During Planned or Unexpected Pregnancy

Study Overview
=================
Brief Summary
-----------------
The objective is to evaluate the potential effect of exposure to dupilumab in pregnancy compared to the primary comparison group of disease-matched pregnant women who are not exposed to dupilumab, and the secondary comparison group of healthy pregnant women. The primary outcome of the study is major structural defects, and the secondary outcomes of the study are spontaneous abortion/miscarriage, stillbirth, elective termination/abortion, premature delivery, small for gestational age, pattern of 3 or more minor structural defects, postnatal growth of live born children to 1 year of age, postnatal serious or opportunistic infections in live born children to 1 year of age, and hospitalizations in live children up to 1 year of age.

Official Title
-----------------
Post-Authorization Safety Study to Monitor Pregnancy and Infant Outcomes Following Administration of Dupilumab During Planned or Unexpected Pregnancy in North America

Conditions
-----------------
Atopic Dermatitis (AD), Asthma

Intervention / Treatment
-----------------
* Drug: dupilumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Cohort 1: Dupilumab-Exposed Cohort Pregnant women Exposure to dupilumab for the treatment of the approved indications of atopic dermatitis (AD) or asthma, 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. Cohort 2: Disease-Matched Comparison Cohort (Comparison Group 1) Pregnant women Diagnosed with a dupilumab-approved indications of moderate-to-severe AD without asthma or moderate-to-severe asthma; frequency matched to the exposed group by disease indication, with the indication and severity validated by medical records when possible. No exposure to dupilumab any time in the current pregnancy or within 10 weeks of the first day of the LMP and may or may not have taken another medication for their disease in the current pregnancy. Cohort 3: Healthy Comparison Cohort (Comparison Group 2): Pregnant women Key Exclusion Criteria: Cohort 1: Dupilumab-Exposed Cohort Women who have first contact with the project after prenatal diagnosis of any major structural defect Women who have used dupilumab for an indication other than asthma or AD Cohort 2: Disease-Matched Comparison Cohort (Comparison Group 1): Women who have first contact with the project after prenatal diagnosis of any major structural defect Exposure to dupilumab within 10 weeks of LMP or anytime during the current pregnancy Cohort 3: Non-Diseased Comparison Cohort (Comparison Group 2): Exposure to dupilumab within 10 weeks prior to the first day of the LMP Women who have a diagnosis of any dupilumab approved indication Women who have first contact with the project after prenatal diagnosis of any major structural defect NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: Dupilumab-Exposed Cohort<br>Pregnant women with approved indications exposed to dupilumab during pregnancy | Drug: dupilumab<br>* Dupilumab cohort<br>* Other names: SAR23189;|
| Cohort 2: Disease-Matched Comparison Cohort<br>Pregnant women with approved indications not exposed to dupilumab during pregnancy | |
| Cohort 3: Healthy Comparison Cohort<br>Pregnant women who are not diagnosed with any dupilumab-approved indications, and not exposed to dupilumab during pregnancy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major structural defects | Defined and classified using the Centers for Disease Control and Prevention (CDC) coding manual that is used for the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of major structural defects | Up to 1 Year of Age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of spontaneous abortion or miscarriage | Defined as non-deliberate fetal death | Up to 20 weeks post-LMP (Last Menstrual period) | 
| Incidence of stillbirth | Defined as non-deliberate fetal death | At or after 20 weeks post-LMP | 
| Incidence of elective termination/abortion | Defined as deliberate discontinuation of pregnancy through medication or surgical procedures | Up to 9 months | 
| Incidence of premature delivery | Defined as live birth prior to 37.0 weeks gestation as counted from LMP (or ultrasound-adjusted date) | Prior to 37 weeks of gestation | 
| Incidence of small for gestational age | Defined as birth size (weight, length or head circumference) less than or equal to the 10th centile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants | At Birth | 
| Incidence of a pattern of 3 or more minor structural defects | Identified by a study examiner: Defined as 1 of the defects representing a structural anomaly which has neither cosmetic nor functional significance to the child | Between Birth and Up to 1 Year of Age | 
| Postnatal growth deficiency | Defined as postnatal size (weight, length or head circumference) less than or 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 | 
| Incidence of postnatal serious or opportunistic infections in live born children | Defined as any infection resulting in hospitalization | Up to 1 Year of Age | 
| Incidence of hospitalizations in live born children | Defined as any hospitalization of the infant within the first year of life after discharge following delivery | Up to 1 Year of Age |