A Study to Learn How Nusinersen (Spinraza) Affects Participants With Spinal Muscular Atrophy (SMA) Who Took it Before or During Pregnancy And About The Health of Their Babies

Spinraza (Nusinersen) SMA Pregnancy Exposure Study Within Existing SMA Registries

In this study, researchers will know more about the effects of nusinersen, also known as Spinraza®, in pregnant participants with spinal muscular atrophy, also known as SMA. This is a drug available for doctors to prescribe for people with SMA. Due to the current treatment options that exist, people with SMA may now reach the age where they can become pregnant. But, there is not enough information known yet about what the effects of nusinersen may be on pregnant people with SMA or on their babies.

This is known as an "observational" study, which collects health information about study participants without changing their medical care. The pregnant participants for this study will be found using 3 different groups of SMA study research centers:

• ISMAR-US (International SMA Registry in the United States)
• UK Adult SMA-REACH (Adult SMA Research and Clinical Hub in the United Kingdom)
• SMArtCARE (Austria, Germany, and Switzerland)

The main goal of this study is to collect birth and health information from 3 groups of participants and their babies. These groups are:

• Those who received nusinersen 14 months before the first day of their last period before getting pregnant
• Those who received nusinersen 14.5 months before the day they got pregnant
• Those who received nusinersen during any time in their pregnancy

The main questions researchers want to learn about in this study are:

• Loss of pregnancy overall
• Loss of pregnancy before the baby was 20 weeks old
• Loss of pregnancy after the baby becomes 20 weeks old
• Live births
• Loss of the baby after birth
• Babies who have problems in their body that develop during pregnancy
• Babies who are small for their age while in the participant's uterus
• Pregnancy that happens outside of the uterus
• How many participants die during pregnancy, while the baby is being born, and up to 12 weeks after delivering the baby
• Babies who develop problems in their body after birth

Researchers will also compare this information to people without SMA who have not received nusinersen.

This study will be done as follows:

• Information will start being collected when the participant decides to join the study.
• Participants will be contacted at each trimester (about every 3 months) to learn about their health and pregnancy.
• Participants' doctors will be contacted at each trimester, when the participants are about 6 or 7 months pregnant, and about 4 weeks after the delivery of the baby.
• The babies' doctors will be contacted when the baby is 1, 2, 6, 12, 18, and 24 months old.
• Each participant will be in the study until the end of their pregnancy and for up to 12 weeks after delivery. Each baby will be in the study for up to 2 years after birth.
• The study overall will last at least 10 years from when the first participant joins the study.

Study Overview

• Status: Recruiting
• Conditions: Muscular Atrophy, Spinal
• Intervention / Treatment: Other: No Intervention

Detailed Description

The primary objectives of the study are to prospectively evaluate pregnancy complications and outcomes in participants with SMA, birth outcomes and adverse effects in infants born to participants with SMA, who were exposed to nusinersen up to 14 months prior to the first day of their last menstrual period (LMP) before conception, 14.5 months before the date of conception, and/or at any time during their pregnancy. The secondary objective of the study is to evaluate pregnancy outcomes in participants with SMA exposed to nusinersen as compared with participants without SMA who were not exposed to nusinersen (e.g., participants from external, general population comparators).

• Study Type: Observational
• Enrollment (Estimated): 20

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

• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Recruiting
    • North Bristol NHS Trust
    • Contact: Phone Number: 0117 950 5050
    • Principal Investigator: Andria Merrison
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • Recruiting
      • University College London Hospitals NHS Foundation Trust
      • Principal Investigator: Matt Parton
      • Contact: Phone Number: 020 3456 7890
    • London, Greater London, United Kingdom, SW17 0QT
      • Recruiting
      • St George's University NHS Foundation Trust
      • Contact: Phone Number: 020 8672 1255
      • Principal Investigator: Clare Galtrey
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Recruiting
      • The Northern Care Alliance NHS Foundation Trust
      • Principal Investigator: James Lilleker
      • Contact: Phone Number: 0161 789 7373
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: Phone Number: 023 8077 7222
      • Principal Investigator: Annamaria Kiss-csenki
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Recruiting
      • Nottingham University Hospitals Trust
      • Contact: Phone Number: 0115 969 1169
      • Principal Investigator: Saam Sedehizadeh
  • Shropshire
    • Oswestry, Shropshire, United Kingdom, SY10 7AG
      • Recruiting
      • The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust
      • Principal Investigator: Tracey Willis
      • Contact: Phone Number: 01691 404000
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2SB
      • Recruiting
      • Sheffield Teaching Hospitals NHS Foundation Trust
      • Principal Investigator: Channa Hewamadduma
      • Contact: Phone Number: 0114 271 7000
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7ND
      • Recruiting
      • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
      • Contact: Phone Number: 0191 233 6161
      • Principal Investigator: Chiara Marini-Bettolo
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2GW
      • Recruiting
      • University Hospitals Birmingham NHS Foundation Trust
      • Contact: Phone Number: (0121) 432 3232
      • Principal Investigator: Nicholas Davies
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Neuroscience Health Center
      • Contact: Phone Number: 650-725-7622
      • Principal Investigator: John W. Day
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Phone Number: 617-355-8036
      • Principal Investigator: Basil T. Darras
    • Cambridge, Massachusetts, United States, 02142
      • Active, not recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Phone Number: 212-305-1319
      • Principal Investigator: Michio Hirano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant participants with SMA who are exposed to nusinersen from the UK Adult SMA REACH, ISMAR - US, and SMArtCARE registries will be enrolled to obtain information on effects of nusinersen on pregnancy complications and outcomes.

Description

Key Inclusion Criteria:

• Participant who is currently pregnant (or was pregnant during the relevant exposure window) and enrolled in the United States (US) network of the ISMAR registry, the United Kingdom (UK) Adult SMA REACH, or the Germany, Austria, or Switzerland network of the SMArtCARE registry
• Genetic documentation of spinal muscular atrophy linked to chromosome 5q (5q SMA)
• Documentation that the participant was exposed to nusinersen up to 14 months prior to the first day of their LMP before conception, 14.5 months before conception, and/or at any time during their pregnancy

Key Exclusion Criteria:

• Treatment with risdiplam at any time from the first day of their LMP, 2 weeks prior to the date of conception (approximately 5 half-lives), and/or plans to receive treatment with risdiplam during pregnancy

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Nusinersen Treated Participants; Pregnant participants with SMA who are exposed to nusinersen during the relevant window defined as 14 months prior to the first day of the participant's last menstrual period before conception, 14.5 months before conception and anytime during pregnancy and are enrolled in the registries, International Spinal Muscular Atrophy Registry (ISMAR), Adult SMA REACH and SMArtCARE will be followed prospectively up to 3 months post-delivery, the infants will be followed up to 2 years post-delivery and the available data is collected retrospectively.

Other: No Intervention; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Pregnancy Terminations	Pregnancy termination is defined as any induced or voluntary fetal loss during pregnancy.	Up to 10 years
Number of Spontaneous Abortions	Spontaneous abortion is defined as any loss of a fetus due to natural causes at <20 weeks of gestation.	Up to 10 years
Number of Fetal Deaths	Fetal deaths include early fetal loss which is fetal death occurring at ≥20 weeks but <28 weeks of gestation and late fetal loss which is fetal death occurring at ≥28 weeks of gestation.	Up to 10 years
Number of Live Births	Live births include premature births which is defined as delivery at <37 weeks of gestation, full term birth which is defined as delivery at ≥37 weeks of gestation.	Up to 10 years
Number of Neonatal, Perinatal, and Infant Deaths	Neonatal death is defined as death occurring in a newborn prior to 28 days after birth. Perinatal death is defined as death occurring at or after 28 days and prior to 12 weeks after birth. Infant death is defined as death occurring between 12 and 52 weeks after birth, inclusive.	Up to 10 years
Number of Major Congenital Malformations (MCMs)	MCMs (interchangeably referred to as congenital malformations, congenital anomalies, and birth defects) are abnormalities in structural development that are medically or cosmetically significant, are present at birth, and persist in postnatal life unless or until repaired.	Up to 10 years
Number of Infants Small for Gestational Age Birth	Birth weight will be classified as small for gestational age (<10th percentile), appropriate (10th-90th percentile), or large (>90th percentile).	Up to 10 years
Number of Ectopic and Molar Pregnancies	Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterine cavity. Molar pregnancy is defined as genetically abnormal conceptions characterized by abnormal chorionic villi, trophoblastic hyperplasia, poor fetal development, and an increased risk of malignant disease development.	Up to 10 years
Number of Maternal Deaths	Maternal deaths during pregnancy, labor, delivery, or up to 12 weeks after delivery will be reported.	Up to 10 years
Number of Infants With Abnormal Postnatal Growth and Development and Neurobehavioral Impairment	Abnormal postnatal growth and development and neurobehavioral impairment in infants up to 24 months of age will be reported.	Up to 10 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): October 31, 2032
• Study Completion (Estimated): October 31, 2033

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal
• Other Study ID Numbers: CH-SPN-12180; 232SM405 (Other Identifier: Biogen)

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