A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)

NCT05067790 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: 232SM3032021-001294-232023-505639-11
• Study Type: interventional
• Target: 45
• Locations: 9 countries
• Sites: 44

Brief Summary

In this study, researchers will learn more about the use of a higher dose of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on teenagers and adults who are unable to walk on their own and who have previously taken another drug for SMA called risdiplam. The main goal of this study is to learn about the effect of high dose (HD) nusinersen on muscle and movement ability (motor function) in SMA. The main question that researchers want to answer is: \- How do the scores of a movement test called the Revised Upper Limb Module change from the start of treatment? The Revised Upper Limb Module is a test used to measure a participant's ability to do specific tasks that involve their shoulders, arms, wrist, elbows, and hands. It measures the changes in their abilities over time. Researchers will also learn more about the safety of HD 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.
• After screening, participants will enter the Core Treatment period.
• At the start of the Core Treatment period, they will receive 2 "loading" doses of nusinersen. These are 50 mg doses of nusinersen given 2 weeks apart.
• Afterwards, they will continue to receive "maintenance" doses of nusinersen once every 4 months. These doses will be 28 mg.
• The Core Treatment period will last about 2 years, with a follow-up visit 4 months after the last dose.
• Participants who complete the Core Treatment period will have the option to continue receiving 28 mg of nusinersen in the Long-Term Extension (LTE) period for about 2 years. There will also be a follow-up visit 4 months after the last dose.
• Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
• In total, participants will have up to 18 study visits. They will also be called by researchers after each dose of nusinersen.
• Participants will stay in the study for about 4.5 years if they complete both the Core Treatment and LTE periods.

Conditions

Spinal Muscular Atrophy

Outcome Measures

Primary Outcomes (1)

• Change in Total Revised Upper Limb Module (RULM) Score

  The RULM is being utilized to assess upper limb functional abilities of participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.

  Up to Day 855

Secondary Outcomes (2)

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

  Up to Day 1695

• Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline

  Up to Day 1695

Study Arms (1)

Higher Dose Nusinersen

EXPERIMENTAL

All participants in the core study period, previously treated with risdiplam (nusinersen-naive participants and nusinersen-experienced participants), will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months. Following the core study period, participants may be given the opportunity to receive maintenance doses of 28 mg nusinersen administered approximately every 4 months up to 2 years during the optional long-term extension (LTE) period.

Drug: Nusinersen

Interventions

Nusinersen DRUG

Administered as specified in the treatment arm

Also known as: BIIB058, Spinraza

Higher Dose Nusinersen

Eligibility Criteria

• Age: 15 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
• Diagnosis of later-onset SMA with symptom onset at age \>6 months.
• Aged ≥15 to ≤50 years at the time of informed consent
• Body weight \>20 kg.
• Received oral risdiplam per the approved label or per the managed access program as follows
• Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment.
• Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment.
• Able to perform the age-appropriate functional assessments in the study.
• RULM entry item A score ≥3.
• RULM total score ≥5 and ≤30 at Screening.
• Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
• Willing to stop risdiplam treatment.
• Willing and able to start treatment with HD nusinersen.

You may not qualify if:

• Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
• Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
• Permanent tracheostomy or permanent ventilation at Screening.
• The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
• History of bacterial meningitis, viral encephalitis, or hydrocephalus.
• Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
• Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
• Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.

Sponsors & Collaborators

• Biogen: lead

Study Sites (44)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Loma Linda University Children's Hospital

Loma Linda, California, 92354, United States

Location

Stanford Neuroscience Health Center

Palo Alto, California, 94304, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20037, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30329, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115-5724, United States

Location

Memorial Healthcare

Owosso, Michigan, 48867, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Forest University - School of Medicine - Central

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Neurology Rare Disease Center

Denton, Texas, 76208, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, 5403900, Brazil

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum rechts der Isar der TU Muenchen

Munich, Bavaria, 81675, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, Hesse, 35392, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Charité - Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Semmelweis Egyetem

Budapest, 1085, Hungary

Location

Ospedale Pediatrico Bambino Gesù

Rome, Roma, 165, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Fondazione Serena Onlus - Centro Clinico Nemo

Milan, 20162, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 168, Italy

Location

Ospedale S G Battista Molinette

Torino, 10126, Italy

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

NHO Osaka Toneyama Medical Center

Toyonaka-shi, Osaka, 560-8552, Japan

Location

Szpital Specjalistyczny im. L.Rydygiera w Krakowie

Krakow, 31-826, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, 02-091, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, 8950, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Links

• Disclaimer: Residents in the United States may click here to find out more about participation in this trial.

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 5, 2021
• Study Start: January 21, 2022
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): June 14, 2027
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (19); ES (2); IT (5); DE (7); JP (2); BE (2); PL (4); HU (1); BR (2)