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

Official title

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

Overview

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.

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).

Interventions

• Other No Intervention
  Administered as specified in the treatment arm.

Primary outcome measures

• Number of Pregnancy Terminations [Time frame: Up to 10 years]
• Number of Spontaneous Abortions [Time frame: Up to 10 years]
• Number of Fetal Deaths [Time frame: Up to 10 years]
• Number of Live Births [Time frame: Up to 10 years]
• Number of Neonatal, Perinatal, and Infant Deaths [Time frame: Up to 10 years]
• Number of Major Congenital Malformations (MCMs) [Time frame: Up to 10 years]
• Number of Infants Small for Gestational Age Birth [Time frame: Up to 10 years]
• Number of Ectopic and Molar Pregnancies [Time frame: Up to 10 years]
• Number of Maternal Deaths [Time frame: Up to 10 years]
• Number of Infants With Abnormal Postnatal Growth and Development and Neurobehavioral Impairment [Time frame: Up to 10 years]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 10 centers

• University College London Hospitals NHS Foundation Trust — London
• St George's University NHS Foundation Trust — London
• The Northern Care Alliance NHS Foundation Trust — Salford
• University Hospital Southampton NHS Foundation Trust — Southampton
• Nottingham University Hospitals Trust — Nottingham
• The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust — Oswestry
• Sheffield Teaching Hospitals NHS Foundation Trust — Sheffield
• The Newcastle upon Tyne Hospitals NHS Foundation Trust — Newcastle upon Tyne
• … and 2 more centers

United States · 4 centers

• Stanford Neuroscience Health Center — Palo Alto
• Boston Children's Hospital — Boston
• Research Site — Cambridge
• Columbia University Irving Medical Center — New York

Identifiers

NCT: NCT05789758 · CH-SPN-12180 · 232SM405

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗