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)

NCT04729907 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 232SM3022023-505637-27
• Study Type: interventional
• Target: 115
• Locations: 15 countries
• Sites: 36

Brief Summary

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.

Conditions

Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (13)

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

  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.

  Up to Day 1921

• Change from Baseline in Growth Parameters

  Growth parameters will be assessed by measuring body length or height (if feasible and appropriate), ulnar length (all participants), and head circumference, chest circumference, and arm circumference (all participants 3 years of age and younger) in centimeters.

  Up to Day 1921

• Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters

  Up to Day 1921

• Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)

  Up to Day 1921

• Number of Participants With Shifts from Baseline in Vital Signs

  Up to Day 1921

• Change from Baseline in Activated Partial Thromboplastin Time (aPTT)

  Up to Day 1921

• Change from Baseline in Prothrombin Time (PT)

  Up to Day 1921

• Change from Baseline in International Normalized Ratio (INR)

  Up to Day 1921

• Change from Baseline in Urine Total Protein

  Up to Day 1921

• Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age

  For participants 2 years of age and younger, the Hammersmith Infant Neurological Exam (HINE) Sections 1 and 3 will be conducted. This standard examination (developed by \[Dubowitz and Dubowitz 1981\]) is a quantitative scorable method for assessing the neurological development of infants between 2 and 24 months of age. The examination includes assessment of cranial nerve functions, posture, movements, tone, and reflexes. The HINE Section 1 form utilized in ONWARD contains 26 items and the Section 3 form utilized contains 3 items. For HINE Section 1 items, each item is scored 0-3. For HINE Section 3 items, scoring is variable (1-4, 1-5, or 1-6). Higher scores indicate better neurological function.

  Up to Day 1921

• Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age

  For all participants \>2 years of age, standard neurological examinations, which include assessments of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes, will be conducted.

  Up to Day 1921

• Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements

  Up to Day 1921

• Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec

  Up toDay 1921

Secondary Outcomes (13)

• Total Number of New World Health Organization (WHO) Motor Milestones

  Up to Day 1921

• Number of Participants Who Used Respiratory Support, by Type

  Up to Day 1921

• Number of Hours Per Day of Respiratory Support

  Up to Day 1921

• Number of Days That Respiratory Support Is Used

  Up to Day 1921

• Time to Death (Overall Survival)

  Up to Day 1921

Study Arms (2)

BIIB058 28 mg (Prior Maintenance Dose 28 mg)

EXPERIMENTAL

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.

Drug: Nusinersen

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

EXPERIMENTAL

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.

Drug: Nusinersen

Interventions

Nusinersen DRUG

Administered as specified in the treatment arm

Also known as: BIIB058, Spinraza

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

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Biogen: lead

Study Sites (37)

Stanford University Medical Center

Sacramento, 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, 60611-260, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Children's Medical Center

Plano, Texas, 75024, United States

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, 5403900, Brazil

Location

London Health Sciences Centre (LHSC) - Children's Hospital

London, Ontario, N6A 5W9, Canada

Location

Clinica MEDS La Dehesa

Santiago, 7691236, Chile

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Guangzhou Woman and Children's Medical Center

Guangzhou, Guangdong, 510623, China

Location

The Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

Location

Hospital Universitario San Ignacio

Bogotá, 110231, Colombia

Location

Tallinn Children's Hospital

Tallinn, 13419, Estonia

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, Hesse, 35392, Germany

Location

Fondazione Serena Onlus - Centro Clinico Nemo

Milan, 20162, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 168, Italy

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Hyogo Medical University Hospital

Nishinomiya-shi, Hyōgo, 663-8501, Japan

Location

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo-To, 162-8666, Japan

Location

Saint George University Hospital Medical Center

Beirut, 11 00 2807, Lebanon

Location

Instituto Nacional de Pediatria

Mexico City, Mexico City, 4530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez

Mexico City, Mexico City, 6720, Mexico

Location

Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, 44280, Mexico

Location

Russian Children Neuromuscular Center of Veltischev

Moskva, 125412, Russia

Location

Regional Pediatric Clinical Hospital #1

Yekaterinburg, 620149, Russia

Location

King Fahad Specialist Hospital

Dammam, 31444, Saudi Arabia

Location

National Guard Health Affairs: King Abdulaziz Medical City

Jeddah, 21423, Saudi Arabia

Location

King Faisal Specialist Hospital & Research Center

Riyadh, 11211, Saudi Arabia

Location

Hospital Sant Joan de Deu

Esplugues Del Llobregat, Barcelona, 8950, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Links

• SMA Europe
• CureSMA
• Muscular Dystrophy Association

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 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: January 29, 2021
• Study Start: April 19, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

ME (3); CA (1); CN (3); DE (2); JP (3); ES (3); IT (2); SA (3); RU (2); CL (1); LE (1); TW (2); BR (2); CO (1); US (7)