Clinical trial NCT05789758: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2023-03-29
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of Pregnancy Terminations
timeFrame: Up to 10 years
measure: Number of Spontaneous Abortions
timeFrame: Up to 10 years
measure: Number of Fetal Deaths
timeFrame: Up to 10 years
measure: Number of Live Births
timeFrame: Up to 10 years
measure: Number of Neonatal, Perinatal, and Infant Deaths
timeFrame: Up to 10 years
measure: Number of Major Congenital Malformations (MCMs)
timeFrame: Up to 10 years
measure: Number of Infants Small for Gestational Age Birth
timeFrame: Up to 10 years
measure: Number of Ectopic and Molar Pregnancies
timeFrame: Up to 10 years
measure: Number of Maternal Deaths
timeFrame: Up to 10 years
measure: Number of Infants With Abnormal Postnatal Growth and Development and Neurobehavioral Impairment
timeFrame: Up to 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Cambridge
country: United States
facility: Research Site
state: Massachusetts
city: London
country: United Kingdom
facility: St George's University NHS Foundation Trust
state: Greater London
city: Salford
country: United Kingdom
facility: The Northern Care Alliance NHS Foundation Trust
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals Trust
state: Nottinghamshire
city: Oswestry
country: United Kingdom
facility: The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust
state: Shropshire
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
state: South Yorkshire
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: