A Study to Learn About the Effect of Nusinersen (BIIB058) Given as Injections to Children With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec (RESPOND)

NCT ID: NCT04488133

Last Updated: 2025-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-04

Study Completion Date

2025-10-09

Brief Summary

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In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on children under the age of 3 who were previously treated with the gene therapy onasemnogene abeparvovec but are still facing health challenges related to their disease.

The main goal of the study is to learn about the effect nusinersen has on muscle and movement ability (motor function). The main question researchers want to answer is:

\- What score do participants have on the HINE Section 2 Motor Milestones test after treatment?

The Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones is an assessment that tests movements in different positions. This includes grasping, kicking, head control, rolling, sitting, crawling, standing, and walking.

Researchers will use a group of tests to study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing.

Researchers will also learn more about the safety of nusinersen. They will check participants for adverse events and changes in vital signs, heart tests, and laboratory tests including blood and urine tests.

The study will be done as follows:

* Participants will be screened to check if they can join the study.
* Each participant will receive 4 initial doses of 12 mg of nusinersen on Days 1, 15, 29, and 64 of the Treatment Period. Then, they will receive 12 mg doses once every 4 months.
* The total number of doses of nusinersen will be 9.
* 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 95 weeks (close to 2 years).
* There will be a follow-up safety period that lasts about 4 months.
* In total, participants will have up to 14 study visits. Participants will stay in the study for up to 115 weeks.

Detailed Description

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The primary objective of this study is to evaluate the clinical outcomes following treatment with nusinersen in participants with spinal muscular atrophy (SMA) who previously received onasemnogene abeparvovec.

The secondary objectives of this study are to evaluate the safety and tolerability; clinical outcomes and pharmacodynamics (PD) of nusinersen treatment in participants with SMA who previously received onasemnogene abeparvovec.

Conditions

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Muscular Atrophy, Spinal

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nusinersen 12 mg

Participants will receive Nusinersen 12 milligrams (mg) via intrathecal (IT) injection as loading doses on Days 1, 15, 29, and 64 followed by maintenance doses, every 4 months, on Days 183, 302, 421, 540 and 659.

Group Type EXPERIMENTAL

Nusinersen

Intervention Type DRUG

Administered as specified in the treatment arm.

Interventions

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Nusinersen

Administered as specified in the treatment arm.

Intervention Type DRUG

Other Intervention Names

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ISIS 396443 BIIB058 Spinraza

Eligibility Criteria

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Inclusion Criteria

For all participants:

* Genetic documentation of 5q SMA homozygous gene survival motor neuron 1 (SMN1) deletion or mutation, or compound heterozygous mutation
* SMN2 copy number of ≥1
* ≤36 months of age at the time of first Nusinersen dose
* Must have previously received onasemnogene abeparvovec per the approved label or local/regional regulations ≥2 months prior to first Nusinersen dose
* Must have suboptimal clinical status per the Investigator

Additional Criteria for Subgroups A and B:

* \<300 days of age at the time of first Nusinersen dose
* SMN2 copy number of 2

Additional Criteria for Subgroup A:

* SMA symptom onset ≤4 months (120 days) of age
* Must have received intravenous (IV) onasemnogene abeparvovec at \>6 weeks to ≤6 months (43 days to 180 days) of age
* Must have received IV onasemnogene abeparvovec after SMA symptom onset

Additional Criteria for Subgroup B:

* Must have received IV onasemnogene abeparvovec at ≤6 weeks (42 days) of age

Exclusion Criteria

For all participants:

* Prior exposure to Nusinersen
* Ongoing severe or serious AEs related to onasemnogene abeparvovec
* Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to study; any prior or current treatment with any survival motor neuron 2 (SMN2)-directed splicing modifier; prior antisense oligonucleotide treatment or cell transplantation; gene therapy for the treatment of SMA other than onasemnogene abeparvovec. Note: treatment with onasemnogene abeparvovec as part of an investigational study is allowed

Additional Criteria for Subgroups A and B:

* Weight-for-age is below the third percentile, based on WHO Child Growth Standards at the time of receiving onasemnogene abeparvovec. Adjustments for the gestational weight of premature babies enrolled in Subgroups A and B are allowed provided IV onasemnogene abeparvovec was dosed per the approved label or per local/regional regulations.
Minimum Eligible Age

2 Months

Maximum Eligible Age

36 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

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Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, United States

Site Status

Stanford Neuromuscular Research

Palo Alto, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Oregon Health and Science University (OHSU)

Portland, Oregon, United States

Site Status

Children's Hospital Philadelphia - Neurology

Philadelphia, Pennsylvania, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Schneider Children's Medical Center

Petah Tikva, , Israel

Site Status

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Milan, Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status

Hospital Sant Joan de Déu

Esplugues Del Llobregat, Barcelona, Spain

Site Status

Hospital Universitario La paz

Madrid, , Spain

Site Status

Countries

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United States Germany Israel Italy Spain

References

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Proud CM, Finkel RS, Parsons JA, Masson R, Brandsema JF, Kuntz NL, Foster R, Li W, Littauer R, Sohn J, Fradette S, Youn B, Paradis AD. Open-label phase 4 trial evaluating nusinersen after onasemnogene abeparvovec in children with spinal muscular atrophy. J Clin Invest. 2025 Sep 16:e193956. doi: 10.1172/JCI193956. Online ahead of print.

Reference Type DERIVED
PMID: 40956616 (View on PubMed)

Related Links

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Other Identifiers

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2020-003492-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505640-18

Identifier Type: OTHER

Identifier Source: secondary_id

232SM404

Identifier Type: -

Identifier Source: org_study_id

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