A Study of Spinraza (Nusinersen) Exposure in Pregnant Women With Spinal Muscular Atrophy (SMA) Within Existing SMA Registries

Study Overview
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Brief Summary
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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).

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

Conditions
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Muscular Atrophy, Spinal

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant who is currently pregnant (or was pregnant during the relevant exposure window) and enrolled in the United Kingdom (UK), United States (US), or Italy network of the ISMAR registry 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 54 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Nusinersen Treated Participants<br>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) 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<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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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 |