Pregnancy Exposure Registry for Vumerity (Diroximel Fumarate)

Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Diroximel Fumarate; Drug: Dimethyl Fumarate; Drug: Avonex; Biological: Tysabri

• Study Type: Observational
• Enrollment (Estimated): 908

Contacts and Locations

• Study Contact: Name: US Biogen Clinical Trial Center; Phone Number: 866-633-4636; Email: clinicaltrials@biogen.com
• Study Contact Backup: Name: Global Biogen Clinical Trial Center; Email: clinicaltrials@biogen.com

Study Locations

• Germany
  • Nordrhein Westfalen
    • Bochum, Nordrhein Westfalen, Germany, 44791
      • Recruiting
      • Katholisches Klinikum Bochum
      • Contact: Phone Number: +492345092420
      • Principal Investigator: Kerstin Hellwig
• Ireland
  • Dublin, Ireland, DO4 T6F4
    • Recruiting
    • St Vincent's University Hospital
    • Contact: Phone Number: +35312773592
    • Principal Investigator: Christopher McGuigan
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
    • Contact: Phone Number: +34913368397
    • Principal Investigator: Lucienne Costa-Frossard
• United States
  • North Carolina
    • Durham, North Carolina, United States, 27703
      • Recruiting
      • IQVIA US Office
      • Contact: Phone Number: 833-569-2635
      • Principal Investigator: Sydney Willis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include pregnant female participants with MS who were exposed to DRF at any time from 2 weeks after the first day of their LMP up through any time during pregnancy and compared with pregnancies among women with MS who were exposed to DMF, women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries), women with MS who were unexposed to DMTs, and women without MS.

Participants will be classified into 2 enrolment types, Prospective and Retrospective. Prospective registration:a report of a pregnancy enrolled prior to knowledge of the pregnancy outcome, including prior to the detection of a congenital malformation at prenatal testing. Women who enrol after any knowledge of the pregnancy outcome will be enrolled as retrospective cases but will not be included in the primary analysis, i.e.,pregnancies with a prenatal testing result indicative of any congenital malformation/pregnancies with known outcomes at time of initial report.

Description

Key Inclusion Criteria:

• Participant must have a diagnosis of MS

• Documentation that the participant was one of the following:

  1. 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).
  2. 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Diroximel Fumarate; 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; Administered as specified in the treatment arm.; Other Names: VUMERITY; BIIB098
Disease Modifying Therapy (DMTs) Exposed; 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; Administered as specified in the treatment arm.; Other Names: BG9418; interferon beta-1a; Biological: Tysabri; Administered as specified in the treatment arm.; Other Names: BG00002; Natalizumab
DMTs Unexposed; 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; 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; Administered as specified in the treatment arm.; Other Names: BG00012; DMF; Tecfidera
Women Without MS; 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

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2023
• Primary Completion (Estimated): July 6, 2032
• Study Completion (Estimated): July 6, 2032

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Estimated): May 15, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Relapsing forms of MS
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Natalizumab; Interferon-beta; Dimethyl Fumarate
• Other Study ID Numbers: 272MS401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No