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A Study of Nusinersen Among Participants With Spinal Muscular Atrophy Who Received Onasemnogene Abeparvovec-xioi

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04488133
Recruitment Status : Not yet recruiting
First Posted : July 27, 2020
Last Update Posted : July 27, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:

The primary objective of this study is to evaluate the clinical outcomes following treatment with nusinersen in participants with spinal muscular atrophy (SMA) who previously received onasemnogene abeparvovec-xioi.

The secondary objectives of this study are to evaluate the safety and tolerability; and clinical outcomes following treatment with nusinersen in participants with SMA who previously received onasemnogene abeparvovec-xioi.


Condition or disease Intervention/treatment Phase
Muscular Atrophy, Spinal Drug: Nusinersen Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4 Study of Nusinersen Among Patients With Spinal Muscular Atrophy Who Received Onasemnogene Abeparvovec-xioi
Estimated Study Start Date : February 26, 2021
Estimated Primary Completion Date : September 4, 2024
Estimated Study Completion Date : September 4, 2024


Arm Intervention/treatment
Experimental: Nusinersen 12 mg
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
Administered as specified in the treatment arm.
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza




Primary Outcome Measures :
  1. Total Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones Score [ Time Frame: Up to Day 778 ]
    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.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 778 ]
    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 (including an abnormal assessment such as an abnormal laboratory value), 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.

  2. Number of Participants with Change from Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Day 778 ]
  3. Number of Participants with Change from Baseline in Electrocardiograms (ECGs) [ Time Frame: Up to Day 778 ]
  4. Number of Participants with Change from Baseline in Vital Signs [ Time Frame: Up to Day 778 ]
  5. Number of Participants who Achieved Motor Milestones as Assessed by World Health Organization (WHO) Criteria [ Time Frame: Up to Day 778 ]
    The motor milestones as defined by WHO criteria includes the following six test items: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone.

  6. Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Score [ Time Frame: Up to Day 778 ]
    The CHOP INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4. The total score ranges from 0-64, with higher scores depicting better response.

  7. Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to Day 778 ]
    The HFMSE is a tool used to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale (HFMS) was expanded to include 13 additional items to improve sensitivity for the higher functioning ambulant population. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all activities, with a maximum score of 66 with higher scores depicting better ability to perform activities.

  8. Change from Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 778 ]
    The RULM is developed to assess upper limb functional abilities 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.

  9. Time to Death or Permanent Ventilation [ Time Frame: Up to Day 778 ]
    Permanent ventilation is defined as tracheostomy or ≥16 hours ventilation/day continuously for >21 days in the absence of an acute reversible event.



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Months to 36 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote).
  • Must have previously received onasemnogene abeparvovec-xioi.
  • Participants with suboptimal clinical status per the Investigator.

Key Exclusion Criteria:

  • Prior exposure to nusinersen.
  • Ongoing severe or serious AEs related to onasemnogene abeparvovec-xioi.
  • Use of steroids within 1 month prior to first dose of nusinersen.

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): NCT04488133


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

Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT04488133    
Other Study ID Numbers: 232SM404
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: July 27, 2020
Last Verified: July 2020
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: http://www.biogenclinicaldatarequest.com/

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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