Pregnancy Exposure Registry for Vumerity (Diroximel Fumarate)

Study Overview
=================
Brief Summary
-----------------
The primary objectives of the study are to estimate the risk of major congenital malformations (MCMs) in infants born to women with multiple sclerosis (MS) who were exposed to diroximel fumarate (DRF) at any time from 2 weeks after the first day of their last menstrual period (LMP) up through the first trimester of pregnancy and to comparatively evaluate pregnancy outcomes with MCMs in women with MS who were exposed to DRF at any time from 2 weeks after the first day of their LMP through the first trimester of pregnancy with the following: i) women with MS who were unexposed to disease modifying therapies (DMTs) and, ii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries). The secondary objective of the study is to evaluate pregnancy outcomes in women with DRF exposure at any time from 2 weeks after the first day of their LMP through the end of pregnancy compared with the following: i) women with MS who were unexposed to DMTs, ii) women with dimethyl fumarate (DMF) exposure, iii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries), and iv) women without MS (e.g., women from external, general population comparators).

Official Title
-----------------
Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry

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

Intervention / Treatment
-----------------
* Drug: Diroximel Fumarate
* Drug: Avonex
* Biological: Tysabri
* Drug: Dimethyl Fumarate


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Participant must have a diagnosis of MS Documentation that the participant was one of the following: exposed to DRF at any time from 2 weeks after the first day of their LMP (i.e., conception date) up through any time during pregnancy. (If exact exposure dates are unknown, the reporter must be able to specify or estimate trimester of exposure). unexposed to any DMT during pregnancy, defined as having never received DMT therapy; discontinued treatment with DRF at least 1 day before 2 weeks after the first day of their LMP (i.e., conception date); or discontinued a non Registry-specified MS DMT more than 5 times its half-life prior to 2 weeks after the first day of their LMP (i.e., conception date) Participants with knowledge of the outcome of the pregnancy (e.g., pregnancy loss or live birth) Key Exclusion Criteria: - None NOTE: Other protocol defined Inclusion criteria may apply
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diroximel Fumarate<br>Pregnant women with MS who were exposed to DRF at any time from 2 weeks after the first day of their LMP through the end of pregnancy. | Drug: Diroximel Fumarate<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB098;|
| Disease Modifying Therapy (DMTs) Exposed<br>Pregnant women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries) at any time from 2 weeks after the first day of their LMP through the end of pregnancy. | Drug: Avonex<br>* Administered as specified in the treatment arm.<br>* Other names: interferon beta-1a;Biological: Tysabri<br>* Administered as specified in the treatment arm.<br>* Other names: BG00002;|
| DMTs Unexposed<br>Pregnant women who were unexposed to DMT which is defined as either never received a DMT or discontinued treatment with DRF at least 1 day before 2 weeks after the first day of their LMP or discontinued a non-Registry-specified MS DMT more than 5 times its half-life prior to 2 weeks after the first day of their LMP. | |
| Dimethyl Fumarate<br>Pregnant women with MS who were exposed to DMF at any time from 2 weeks after the first day of their LMP through the end of pregnancy. | Drug: Dimethyl Fumarate<br>* Administered as specified in the treatment arm.<br>* Other names: BG00012;|
| Women Without MS<br>Pregnant women with external, general population comparators. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Major Congenital Malformations (MCMs) | MCMs include abnormalities in structural development that are medically or cosmetically significant are present at birth, and persist in postnatal life unless or until repaired as evaluated by independent advisors used throughout the registry. | Up to 52 weeks postdelivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Elective or Therapeutic Terminations | Elective or therapeutic pregnancy termination is any induced or voluntary fetal loss during pregnancy. It will be subclassified as elective or therapeutic pregnancy terminations as whether it was due to a fatal anomaly or not. | Up to 9 months of pregnancy | 
| Number of Spontaneous Abortions | Spontaneous abortion is defined as any loss of a fetus due to natural causes before 22 weeks of gestation. | Before 22 weeks of gestation | 
| Number of Fetal Deaths Including Still Birth | Fetal death or stillbirth refers to the death of a fetus prior to complete expulsion or extraction from its mother at or after 22 weeks of gestation. Death is indicated by the fact that, after such separation, the fetus does not show any evidence of life (e.g., heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles). Fetal death occurring at or after 22 weeks but before 28 weeks of gestation is considered an early fetal loss. Fetal death occurring at or after 28 weeks is considered a late fetal loss. | At or after 22 weeks of gestation | 
| Number of Live Births | A live birth refers to a complete expulsion or extraction from its mother of a surviving neonate breathing, or showing any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, whether the umbilical cord has been cut or the placenta is attached. Any live birth before 37 weeks of gestation will be considered premature birth. Any live birth at or after 37 weeks but before 42 weeks of gestation will be considered full-term birth. Any live birth at or after 42 weeks of gestation will be considered post-term birth. | Up to delivery (approximately 10 months) | 
| Number of Ectopic Pregnancies |  | Up to 9 months of pregnancy | 
| Number of Molar Pregnancies |  | Up to 9 months of pregnancy | 
| Number of Maternal Deaths | Maternal death is death of a pregnant woman during pregnancy, labor, or delivery. Registry will also report maternal deaths that occur up to 12 weeks postdelivery. | Up to 12 weeks postdelivery | 
| Number of Neonatal Deaths | Neonatal death is death occurring in a neonate prior to 28 days of life. | Prior to 28 days postdelivery | 
| Number of Perinatal Deaths | Perinatal death is death occurring at or after 28 days of life and prior to 12 weeks of life. | At or after 28 days to 12 weeks postdelivery | 
| Number of Infant Deaths | Infant death is death occurring between 12 and 52 weeks of life, inclusive. | Between 12 to 52 weeks postdelivery | 
| Number of Serious or Opportunistic Infections in Liveborn Children |  | Up to 52 weeks postdelivery | 
| Number of Infants with Abnormal Postnatal Growth and Development | Infant growth measurements will be used to estimate gender-specific weight-for-length, head circumference-for-age, length-for-age, and weight-for-age percentiles. Developmental milestones (i.e., social/emotional, language/communication, neurocognitive, movement/physical development) will be used to determine results of infant status (i.e., below, above, or at age-appropriate achievement). | Up to 52 weeks postdelivery | 
| Number of Participants with Pregnancy Complications | Pregnancy complications may include incidences of pre-eclampsia, eclampsia, pregnancy-induced hypertension, preterm labor, gestational diabetes and placenta previa. | Up to 9 months of pregnancy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pregnancy, Relapsing forms of MS