A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam

Spinal Muscular Atrophy Clinical Trial

— ASCEND  

Official title:

A Phase 3b Study to Evaluate Higher Dose Nusinersen (BIIB058) in Patients With Spinal Muscular Atrophy Previously Treated With Risdiplam

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05067790
• Other study ID #: 232SM303
• Secondary ID: 2021-001294-2320
• Status: Recruiting
• Phase: Phase 3
• Start date: January 21, 2022
• Est. completion date: June 14, 2027

Study information

• Verified date: February 2024
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam. The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 14, 2027
• Est. primary completion date: June 14, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 50 Years

Eligibility

Key Inclusion Criteria:

• 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

1. Nusinersen-naive participants must have had prior treatment with risdiplam for =6 months before enrollment.

2. 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.

Key Exclusion Criteria:

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Drug:
• Nusinersen
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Essen	Essen	Nordrhein Westfalen
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Giessen	Hessen
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern
Germany	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg
Hungary	Semmelweis Egyetem	Budapest
Italy	Fondazione Serena Onlus - Centro Clinico Nemo	Milan	Milano
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Ospedale S G Battista Molinette	Torino
Japan	NHO Osaka Toneyama Medical Center	Toyonaka-shi	Osaka-Fu
Japan	Yokohama City University Hospital	Yokohama-shi	Kanagawa-Ken
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	The Ohio State	Columbus	Ohio
United States	Neurology Rare Disease Center	Denton	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Columbia University	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Memorial Healthcare	Owosso	Michigan
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	UW Medicine	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia
United States	Wake Forest University - School of Medicine - Central	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Italy,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 that does not necessarily have a causal relationship with the 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 or 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 1695
Secondary	Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline		Up to Day 1695

External Links

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