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

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ClinicalTrials.gov Identifier: NCT05067790
Recruitment Status : Recruiting
First Posted : October 5, 2021
Last Update Posted : May 13, 2022
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief 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.


Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: Nusinersen Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b Study to Evaluate Higher Dose Nusinersen (BIIB058) in Patients With Spinal Muscular Atrophy Previously Treated With Risdiplam
Actual Study Start Date : January 21, 2022
Estimated Primary Completion Date : June 14, 2027
Estimated Study Completion Date : June 14, 2027


Arm Intervention/treatment
Experimental: Higher Dose Nusinersen
There will be two groups of participants previously treated with risdiplam in the study (nusinersen-naive group and nusinersen-experienced group), who 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.
Drug: Nusinersen
Administered as specified in the treatment arm
Other Names:
  • BIIB058
  • Spinraza




Primary Outcome Measures :
  1. Change in Total Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 855 ]
    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.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 855 ]
    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.

  2. Number of Participants With Change from Baseline in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry [ Time Frame: Up to Day 855 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≥5 to ≤39 years at the time of informed consent for nusinersen-naïve participants.
  • Aged ≥18 to ≤39 years at time of informed consent for nusinersen-experienced participants.
  • 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 and ≤12 months before enrollment.

Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and have been on risdiplam for ≥12 months and ≤18 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 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.
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05067790


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Locations
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United States, Arkansas
Arkansas Children's Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Kapril Arya, MD    501-364-1850    karya@uams.edu   
Contact: Ashley Bryan    501-364-3122    bryanar@archildrens.org   
Principal Investigator: Kapil Arya, MD         
United States, Georgia
Rare Disease Research, LLC Recruiting
Atlanta, Georgia, United States, 30329
Contact: Han Phan, MD    678-883-6897    hphan@rarediseaseresearh.com   
Contact: Kallie Platt    678-883-6897    kallie.platt@rarediseaseresearch.com   
Principal Investigator: Han Phan, MD         
United States, North Carolina
Atrium Health Wake Forest Baptist Recruiting
Winston-Salem, North Carolina, United States, 27101
Contact: Summer Harris    336-716-3919    sdharris@wakehealth.edu   
Principal Investigator: Michael Cartwright, MD, MS         
United States, Pennsylvania
Research Site Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
Children's Hospital of The King's Daughters Recruiting
Norfolk, Virginia, United States, 23507
Contact    757-668-5755    proud.research@chkd.org   
Principal Investigator: Crystal Proud, MD         
Italy
Research Site Recruiting
Milano, Italy, 20133
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
Additional Information:
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT05067790    
Other Study ID Numbers: 232SM303
2021-001294-23 ( EudraCT Number )
First Posted: October 5, 2021    Key Record Dates
Last Update Posted: May 13, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases