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)

NCT04488133 | Completed Phase 4 DMC FDA Drug

• 3 other identifiers: 232SM4042020-003492-182023-505640-18
• Study Type: interventional
• Target: 46
• Locations: 5 countries
• Sites: 15

Brief Summary

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.

Conditions

Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (1)

• Total Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones Score

  Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is the sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability.

  Up to Day 778

Secondary Outcomes (11)

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 778

• Number of Participants with Change from Baseline in Clinical Laboratory Parameters

  Up to Day 778

• Number of Participants with Change from Baseline in Electrocardiograms (ECGs)

  Up to Day 778

• Number of Participants with Change from Baseline in Vital Signs

  Up to Day 778

• Number of Participants who Achieved Motor Milestones as Assessed by World Health Organization (WHO) Criteria

  Up to Day 778

Study Arms (1)

Nusinersen 12 mg

EXPERIMENTAL

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.

Drug: Nusinersen

Interventions

Nusinersen DRUG

Administered as specified in the treatment arm.

Also known as: ISIS 396443, BIIB058, Spinraza

Nusinersen 12 mg

Eligibility Criteria

• Age: 2 Months - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (15)

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, 72202, United States

Location

Stanford Neuromuscular Research

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Oregon Health and Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Children's Hospital Philadelphia - Neurology

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23510, United States

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Schneider Children's Medical Center

Petah Tikva, 4920235, Israel

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Milan, 20133, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Hospital Sant Joan de Déu

Esplugues Del Llobregat, Barcelona, 08950, Spain

Location

Hospital Universitario La paz

Madrid, 28046, Spain

Location

Related Publications (1)

• 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; RESPOND Study Group. Open-label phase IV trial evaluating nusinersen after onasemnogene abeparvovec in children with spinal muscular atrophy. J Clin Invest. 2025 Sep 16;135(22):e193956. doi: 10.1172/JCI193956. eCollection 2025 Nov 17.

  PMID: 40956616 DERIVED

Related Links

• SMA Europe
• CureSMA
• Muscular Dystrophy Association
• Child Neurology Foundation
• Biogen Trial Link

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

nusinersen

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 27, 2020
• Study Start: January 4, 2021
• Primary Completion: October 9, 2025
• Study Completion: October 9, 2025
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); DE (1); US (9); IL (1); IT (2)