A Study to Learn About the Long-Term Safety of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Took Part in an Earlier Nusinersen Trial (ONWARD)

Biogen

Status and phase: Active, not recruiting; Phase 3

Conditions: Muscular Atrophy, Spinal

Treatments: Drug: Nusinersen

Study type: Interventional

Funder types: Industry

Identifiers

NCT04729907

2023-505637-27 (Other Identifier)

232SM302

Details and patient eligibility

About

In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study is an extension study and will enroll only those participants who have completed treatment in the parent study, 232SM203.

The main goal of the study is to learn about the long-term safety of nusinersen. The main questions researchers want to answer are:

• How many participants have adverse events and serious adverse events during the study?
• How do the results of electrocardiograms (ECGs), vital signs, and laboratory tests including blood and urine tests change after treatment?
• How many participants have a low platelet count after treatment?
• How many participants had a change in the time it took for their heart to recharge between beats after treatment?
• How does each participant's height and other measures of growth change after treatment?
• How much do the results of neurological exams that check movement, reflexes, and brain function change after treatment?

Researchers will also learn about the effect of nusinersen on mobility using various tests. They will study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing.

The 232SM302 study will be done as follows:

• Participants will be screened to check if they can join the study.
• Participants will receive their 1st dose of nusinersen in this study about 4 months after their final dose in the parent study.
• Each participant will receive nusinersen once every 4 months during the treatment period.
• Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
• The treatment period will last for up to 64 months (1921 days).
• There will be a follow-up safety period that lasts from 4 to 8 weeks.
• In total, participants will have up to 19 study visits. Participants will stay in the study for close to 6 years.

Full description

The primary objective of this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566).

The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566).

Enrollment: 115 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol

Key Exclusion Criteria:

• Treatment with another investigational therapy or enrollment in another interventional clinical study
• Treatment with an approved therapy for SMA after the Day 302 Visit of Study 232SM203 (NCT04089566)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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115 participants in 2 patient groups

BIIB058 28 mg (Prior Maintenance Dose 28 mg)

Experimental group

Description:

Participants who received maintenance dose of 28 milligrams (mg) nusinersen in study 232SM203 (NCT04089566), will receive maintenance dose of 28 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.

Treatment:

Drug: Nusinersen

BIIB058 50/28 mg (Prior Maintenance Dose 12 mg)

Experimental group

Description:

Participants who received maintenance dose of 12 mg nusinersen in study 232SM203 (NCT04089566), will receive loading dose of 50 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.

Treatment:

Drug: Nusinersen