Extension Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Who Previously Participated in a Study With Nusinersen (ONWARD)
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| ClinicalTrials.gov Identifier: NCT04729907 |
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Recruitment Status :
Enrolling by invitation
First Posted : January 29, 2021
Last Update Posted : August 23, 2023
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Sponsor:
Biogen
Information provided by (Responsible Party):
Biogen
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Brief Summary:
The primary objective of this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566).
The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Muscular Atrophy, Spinal | Drug: Nusinersen | Phase 3 |
Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 172 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Long-Term Extension Study of Nusinersen (BIIB058) Administered at Higher Doses in Participants With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen |
| Actual Study Start Date : | April 19, 2021 |
| Estimated Primary Completion Date : | May 30, 2026 |
| Estimated Study Completion Date : | May 30, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Spinal muscular atrophy
MedlinePlus related topics:
Spinal Muscular Atrophy
Drug Information
available for:
Nusinersen
| Arm | Intervention/treatment |
|---|---|
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Experimental: BIIB058 28 mg (Prior Maintenance Dose 28 mg)
Participants who received maintenance dose of 28 milligram (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 961.
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Drug: Nusinersen
Administered as specified in the treatment arm
Other Names:
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Experimental: BIIB058 50/28 mg (Prior Maintenance Dose 12 mg)
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 961.
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Drug: Nusinersen
Administered as specified in the treatment arm
Other Names:
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Primary Outcome Measures :
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1081 ]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.
- Change from Baseline in Growth Parameters [ Time Frame: Up to Day 1081 ]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.
- Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Day 1081 ]
- Number of Participants With Shifts from Baseline in Electrocardiogram (ECG) [ Time Frame: Up to Day 1081 ]
- Number of Participants With Shifts from Baseline in Vital Signs [ Time Frame: Up to Day 1081 ]
- Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Up to Day 961 ]
- Change from Baseline in Prothrombin Time (PT) [ Time Frame: Up to Day 961 ]
- Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Up to Day 961 ]
- Change from Baseline in Urine Total Protein [ Time Frame: Up to Day 1081 ]
- Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age [ Time Frame: Up to Day 1081 ]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.
- Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age [ Time Frame: Up to Day 1081 ]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.
- Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [ Time Frame: Up to Day 1081 ]
- 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 [ Time Frame: Up to Day 1081 ]
Secondary Outcome Measures :
- Total Number of New World Health Organization (WHO) Motor Milestones [ Time Frame: Up to Day 1081 ]
- Number of Participants Who Used Respiratory Support, by Type [ Time Frame: Up to Day 1081 ]
- Number of Hours Per Day of Respiratory Support [ Time Frame: Up to Day 1081 ]
- Number of Days That Respiratory Support Is Used [ Time Frame: Up to Day 1081 ]
- Time to Death (Overall Survival) [ Time Frame: Up to Day 1081 ]
- Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score [ Time Frame: Up to Day 1081 ]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. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
- Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones [ Time Frame: Up to Day 1081 ]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. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
- Percentage of HINE Section 2 Motor Milestone Responders [ Time Frame: Up to Day 1081 ]Section 2 of HINE is used to assess motor milestones of 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 sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. HINE section 2 motor milestone responder is participant who demonstrates at least 2-point increase in category of ability to kick or increase to maximal score on that category or 1-point increase in motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and among 7 motor milestone categories (excluding voluntary grasp), participant demonstrates improvement in more categories than worsening. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
- Percentage of Time Spent on Ventilation [ Time Frame: Up to Day 1081 ]This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
- Time to Death or Permanent Ventilation [ Time Frame: Up to Day 1081 ]Permanent ventilation is defined as tracheostomy or ≥16 hours of ventilation/day continuously for >21 days in the absence of an acute reversible event. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
- Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to Day 1081 ]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. Participants ≥ 2 years of age (at the time of the study visit) will be evaluated with HFMSE.
- Change from Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 1081 ]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. Participants ≥ 2 years of age (at the time of the study visit) will be evaluated with RULM.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol
Key Exclusion Criteria:
- 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)
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): NCT04729907
Locations
Show 38 study locations
Sponsors and Collaborators
Biogen
Investigators
| Study Director: | Medical Director | Biogen |
Additional Information:
| Responsible Party: | Biogen |
| ClinicalTrials.gov Identifier: | NCT04729907 |
| Other Study ID Numbers: |
232SM302 2020-004708-32 ( EudraCT Number ) |
| First Posted: | January 29, 2021 Key Record Dates |
| Last Update Posted: | August 23, 2023 |
| Last Verified: | August 2023 |
| 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 https://www.biogentrialtransparency.com/ |
| URL: | https://vivli.org/ |
| 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 |