An Observational Study on Teriflunomide-exposed Pregnancies

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To evaluate any potential increase in the risk of major birth defects, in the first year of life, in teriflunomide-exposed pregnancies. Secondary Objective: To evaluate the potential effect of teriflunomide-exposure on other adverse pregnancy outcomes including any potential pattern of minor birth defects, spontaneous abortion, stillbirth, preterm delivery, small for gestational age at birth and at 1 year follow-up.

Detailed Description
-----------------
The total study duration per participant is approximately up to 2 years. This is a prospective, observational study (no intervention), ie, patient registry. The statistical analysis for the cohort study describe baseline characteristics in all three cohorts, and then will compare pregnancy outcomes in cohort 1 to cohort 2 and secondarily to cohort 3. For the registry group, without comparisons, only descriptive statistics of pregnancy outcomes will be summarized.

Official Title
-----------------
Teriflunomide Pregnancy Outcome Exposure Registry: An OTIS Autoimmune Diseases in Pregnancy Project

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: Teriflunomide (HMR1726)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Pregnant women who have provided an oral and/or written consent to enroll no later than 20 completed weeks from last menstrual period (LMP). Pregnant women who agree to the conditions and requirements of the study including the interview schedule, release of medical records, and the physical examination of live born infants (up to 1 year post birth). Pregnant women with a diagnosis of MS and teriflunomide exposure during pregnancy (Cohort 1). Pregnant women with MS but not exposed teriflunomide during pregnancy (Cohort 2). Healthy pregnant women who do not have a known diagnosis of MS and have no known exposure to a known human teratogen during pregnancy (Cohort 3). Exclusion criteria: Pregnant women who come in first contact with the project after prenatal diagnosis of a major structural defect (Cohort 1, 2, 3). This does not apply to the registry group. Pregnant women who first come in contact with the project after 20 completed weeks' gestation (Cohort 1, 2, 3). This does not apply to the registry group. Pregnant women who had previously enrolled in the study for a previous pregnancy (only 1 pregnancy, per woman, maybe registered) (Cohort 1, 2, 3). This does not apply to the registry group. Retrospectively reported cases (Cohort 1, 2, 3). This does not apply to the registry group. Pregnant women with exposures to teriflunomide commencing after the 12th week post-LMP (Cohort 1). This does not apply to the registry group. Pregnant women who had previously been treated with teriflunomide if they had received any dose of the drug within 2 years prior to the index pregnancy and do not have documented blood levels below 0.02 mcg/mL prior to pregnancy (Cohort 2). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 16 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 I<br>Pregnant women with a confirmed diagnosis of multiple sclerosis (MS) and teriflunomide exposure during the current pregnancy | Drug: Teriflunomide (HMR1726)<br>* Pharmaceutical form: tablet Route of administration: oral<br>* Other names: Aubagio;|
| Cohort II<br>Pregnant women with MS not exposed to teriflunomide during the current pregnancy | |
| Cohort III<br>Healthy pregnant women who do not have a known diagnosis of MS and have no known exposure to a known human teratogen | |
| Registry group (not eligible for cohorts)<br>Women who contact the OTIS registry study staff and who do not meet the criteria for the prospective study, for example, at time of contacting the study, having known prenatal diagnosis of congenital defect, or gestation weeks greater than 20 following a first trimester teriflunomide exposure, etc.; these participants will not be included in the primary analysis for the cohort study. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major structural defects in live born infants |  | Up to the infant's first year birthday | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of major structural defects in all pregnancies |  | up to 1 year of age in infant | 
| Specific pattern of 3 or more minor structural defects in live born infants receiving the exam |  | up to one year after birth | 
| Rate of spontaneous abortion |  | date of conception to 20 weeks gestation | 
| Rate of preterm delivery |  | live birth prior to 37 weeks gestation | 
| Proportion of infants who are small for gestational age (less than or equal to the 10th percentile for gestational age and sex) on weight, length, or head circumference |  | at birth | 
| 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 |  | 1 year |