Clinical Trials List
Protocol Number232SM203
NCT Number(ClinicalTrials.gov Identfier)NCT04089566
2020-04-01 - 2026-09-30
Phase II/III
Recruiting2
ICD-9335.10
Spinal muscular atrophy, unspecified
Escalating Dose and Randomized, Controlled Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Biogen Idec Research Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 謝正宜 Division of Rehabilitation Medicine
- WANG-TSO LEE Division of Pediatrics
- 黃信豪 Division of Anesthesia
- Yin-Hsiu Chien Division of General Internal Medicine
- YUNG-LI YANG Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Spinal Muscular Atrophy
Objectives
The primary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with SMA, as measured by change in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) total score (Part B); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) (Parts A and C).
The secondary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A, B and C); to examine the effect of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A and C); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with SMA, to examine the effect of nusinersen administered intrathecally at higher doses compared to the currently approved dose in participants with SMA (Part B).
Test Drug
Nusinersen
Active Ingredient
Nusinersen
Dosage Form
Solution for injection
Dosage
12
Endpoints
Primary Outcome Measures :
Part B Infantile-onset SMA: Change from Baseline in CHOP INTEND Total Score [ Time Frame: Baseline up to Day 183 ]
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.
Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening up to Day 389 ]
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.
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters [ Time Frame: Screening up to Day 302 ]
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) [ Time Frame: Screening up to Day 302 ]
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs [ Time Frame: Screening up to Day 302 ]
Part A and C: Change from Baseline in Body Length/Height [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Head Circumference [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Chest Circumference [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Arm Circumference [ Time Frame: Baseline up to Day 302 ]
Part A and C Later-onset SMA: Change from Baseline in Ulnar Length [ Time Frame: Baseline up to Day 302 ]
Part A and C: Ratio of Weight for Age [ Time Frame: Baseline up to Day 302 ]
Part A and C: Ratio of Weight for Length [ Time Frame: Baseline up to Day 302 ]
Part C: Ratio of Head-to-chest Circumference [ Time Frame: Baseline up to Day 302 ]
Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change from Baseline in Prothrombin Time (PT) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change in Urine Total Protein [ Time Frame: Baseline up to Day 302 ]
Part A and C: Change from Baseline in Neurological Examination Outcomes [ Time Frame: Baseline up to Day 302 ]
Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [ Time Frame: Baseline up to Day 302 ]
Part A and C: 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: Baseline up to Day 302 ]
Part B Infantile-onset SMA: Change from Baseline in CHOP INTEND Total Score [ Time Frame: Baseline up to Day 183 ]
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.
Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening up to Day 389 ]
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.
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters [ Time Frame: Screening up to Day 302 ]
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) [ Time Frame: Screening up to Day 302 ]
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs [ Time Frame: Screening up to Day 302 ]
Part A and C: Change from Baseline in Body Length/Height [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Head Circumference [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Chest Circumference [ Time Frame: Baseline up to Day 302 ]
Part C Infantile-onset SMA: Change from Baseline in Arm Circumference [ Time Frame: Baseline up to Day 302 ]
Part A and C Later-onset SMA: Change from Baseline in Ulnar Length [ Time Frame: Baseline up to Day 302 ]
Part A and C: Ratio of Weight for Age [ Time Frame: Baseline up to Day 302 ]
Part A and C: Ratio of Weight for Length [ Time Frame: Baseline up to Day 302 ]
Part C: Ratio of Head-to-chest Circumference [ Time Frame: Baseline up to Day 302 ]
Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change from Baseline in Prothrombin Time (PT) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Baseline up to Day 269 ]
Part A and C: Change in Urine Total Protein [ Time Frame: Baseline up to Day 302 ]
Part A and C: Change from Baseline in Neurological Examination Outcomes [ Time Frame: Baseline up to Day 302 ]
Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [ Time Frame: Baseline up to Day 302 ]
Part A and C: 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: Baseline up to Day 302 ]
Inclution Criteria
Key Inclusion Criteria:
Part A, B and C:
- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote)
Part A:
Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of age (i.e., later-onset SMA)
Age 2 to ≤ 15 years, inclusive, at the time of informed consent
Part B:
Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset) should have age > 1 week to ≤ 7 months (≤ 210 days) at the time of informed consent
Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
Age 2 to < 10 years at the time of informed consent
Can sit independently but has never had the ability to walk independently
HFMSE score ≥ 10 and ≤ 54 at Screening
Part C:
Participants ≥ 18 years of age at Screening must be ambulatory
Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening
Part A, B and C:
- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote)
Part A:
Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of age (i.e., later-onset SMA)
Age 2 to ≤ 15 years, inclusive, at the time of informed consent
Part B:
Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset) should have age > 1 week to ≤ 7 months (≤ 210 days) at the time of informed consent
Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
Age 2 to < 10 years at the time of informed consent
Can sit independently but has never had the ability to walk independently
HFMSE score ≥ 10 and ≤ 54 at Screening
Part C:
Participants ≥ 18 years of age at Screening must be ambulatory
Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening
Exclusion Criteria
Key Exclusion Criteria:
Part A, B and C:
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 cerebrospinal fluid (CSF) or of an implanted central nervous system (CNS) catheter
Hospitalization for surgery, pulmonary event, or nutritional support within 2 months prior to Screening or planned within 12 months after the participant's first dose
Part A:
Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
Medical necessity for a gastric feeding tube
Treatment with an investigational drug given for the treatment of SMA, 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 any survival motor neuron-2 (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Part B:
Treatment with an investigational drug given for the treatment of SMA, 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 any SMN2-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
Medical necessity for a gastric feeding tube
Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset): Signs or symptoms of SMA present at birth or within the first week after birth.
Part C:
- Concurrent or previous participation and/or administration of nusinersen in another clinical study
Part A, B and C:
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 cerebrospinal fluid (CSF) or of an implanted central nervous system (CNS) catheter
Hospitalization for surgery, pulmonary event, or nutritional support within 2 months prior to Screening or planned within 12 months after the participant's first dose
Part A:
Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
Medical necessity for a gastric feeding tube
Treatment with an investigational drug given for the treatment of SMA, 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 any survival motor neuron-2 (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Part B:
Treatment with an investigational drug given for the treatment of SMA, 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 any SMN2-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
Medical necessity for a gastric feeding tube
Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset): Signs or symptoms of SMA present at birth or within the first week after birth.
Part C:
- Concurrent or previous participation and/or administration of nusinersen in another clinical study
The Estimated Number of Participants
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Taiwan
12 participants
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Global
145 participants
