Phase 3
N=145
Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
Muscular Atrophy, Spinal
Bottom Line
View on ClinicalTrials.gov: NCT04089566 ↗Enrolled (actual)
145
Serious AEs
42.1%
Results posted
Jun 2025
Primary outcome: Primary: Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group — 42.9; 16.9 score on scale — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Nusinersen (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Biogen
- Primary completion
- Feb 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group |
42.9; 16.9 | < 0.0001 sig |
| PRIMARY Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) |
4; 37; 1; 6 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) |
1; 2; 0; 6; 0; 8 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) |
2; 6; 2; 6; 1; 3 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis |
2; 1; 0; 2; 4; 9 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters |
1; 2; 0; 2; 0; 3 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) |
0; 10; 3; 12; 3; 17 | — |
| PRIMARY Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters |
4; 13; 1; 14; 6; 19 | — |
| PRIMARY Parts A and C: Change From Baseline in Growth Parameters (Body Height) |
7.2; 0.8 | — |
| PRIMARY Part C: Change From Baseline in Growth Parameters (Head Circumference) |
2.0 | — |
| PRIMARY Part C: Change From Baseline in Growth Parameters (Chest Circumference) |
2.5 | — |
| PRIMARY Part C: Change From Baseline in Growth Parameters (Arm Circumference) |
-1.0 | — |
| PRIMARY Parts A and C: Change From Baseline in Growth Parameters (Ulnar Length) |
1.8; 0.0 | — |
| PRIMARY Parts A and C: Change From Baseline in Growth Parameters (Weight for Age Percentile) |
12.2; -2.7 | — |
| PRIMARY Part C: Change From Baseline in Growth Parameters (Weight for Length Ratio) |
0.005 | — |
| PRIMARY Part C: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) |
0.0 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) |
0; 5; 0; 1 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) |
0; 0; 0; 1 | — |
| PRIMARY Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) |
0; 3; 0; 0 | — |
| PRIMARY Parts A and C: Change From Baseline in Urine Total Protein |
0.010; -0.692 | — |
| PRIMARY Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs |
0; 1; 0; 1; 0; 1 | — |
| PRIMARY Parts A and C: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements |
0; 2.5 | — |
| PRIMARY Parts 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 |
0; 0 | — |
| SECONDARY Part B Infantile-onset SMA: Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group |
58; 0 | <0.0001 sig |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group |
43.1; 16.5 | <0.0001 sig |
| SECONDARY Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group |
0.06; 0.70 | <0.0001 sig |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
37.3; 38.3 | =0.8484 |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
33.9; 40.0 | =0.1734 |
| SECONDARY Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
0.23; 0.12 | =0.002 sig |
| SECONDARY Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group |
NA; 19.1 | — |
| SECONDARY Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group |
NA; 33.6 | — |
| SECONDARY Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
24.7; NA | — |
| SECONDARY Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
NA; NA | — |
| SECONDARY Part B Later-onset SMA: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
2.6; 3.3 | — |
| SECONDARY Part B Later-onset SMA: Change From Baseline in Revised Upper Limb Module (RULM) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
1.8; 2.5 | — |
| SECONDARY Part B Later-onset SMA: Number of New World Health Organization (WHO) Motor Milestones Achieved Per Participant for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
0.0; 0.3 | — |
| SECONDARY Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
7.9; 8.3; 10.3; 10.1; -0.0; 9.9 | — |
| SECONDARY Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
-5.1; 3.8; -9.6; -6.9; -4.8; 10.4 | — |
| SECONDARY Part B Later-onset SMA: Change From (Ratio to) Baseline in CSF Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
0.32; 0.33 | — |
| SECONDARY Part B Later-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen |
0.28; 0.35 | — |
| SECONDARY Part B: Number of Participants With TEAEs and TESAEs |
22; 45; 7; 14; 18; 30 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) |
0; 2; 0; 0; 7; 17 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) |
6; 13; 1; 1; 1; 2 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Urinalysis |
2; 2; 1; 1; 3; 3 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in CSF Parameters |
4; 3; 1; 0; 0; 1 | — |
| SECONDARY Part B: Number of Participants With Shift From Baseline in ECGs |
2; 7; 0; 0; 9; 10 | — |
| SECONDARY Part B: Number of Participants With Abnormalities in Vital Sign Parameters |
6; 23; 3; 7; 0; 6 | — |
| SECONDARY Part B: Change From Baseline in Growth Parameters (Body Height) |
8.0; 10.25; 11.2; 6.9 | — |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Head Circumference) |
4.52; 5.50 | — |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Chest Circumference) |
5.67; 6.64 | — |
| SECONDARY Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Arm Circumference) |
0.45; 1.16 | — |
| SECONDARY Part B: Change From Baseline in Growth Parameters (Ulnar Length) |
2.8; 1.2 | — |
| SECONDARY Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) |
-6.70; -3.60; 9.1; -0.3 | — |
| SECONDARY Part B: Change From Baseline in Growth Parameters (Weight for Length Percentile) |
-4.23; 6.05 | — |
| SECONDARY Part B: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) |
-0.03; -0.05 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) |
4; 14; 2; 2; 6; 7 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) |
3; 6; 1; 1; 2; 6 | — |
| SECONDARY Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) |
1; 5; 0; 0; 2; 6 | — |
| SECONDARY Part B: Change From Baseline in Urine Total Protein |
-0.130; -3.274; -0.213; 0.004 | — |
| SECONDARY Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs |
0; 1; 0; 0; 1; 0 | — |
| SECONDARY Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements |
4; 0; 0; 0 | — |
| SECONDARY Part B: Percentage of Participants With a Postbaseline QTcF of > 500 Msec and an Increase From Baseline to Any Postbaseline Timepoint in QTcF of > 60 Msec |
8; 0; 0; 0 | — |
| SECONDARY Parts A, B and C: Number of Participants With Hospitalizations |
1; 19; 26; 3; 6; 12 | — |
| SECONDARY Parts A, B and C: Percentage of Time of Hospitalization |
0; 6.4; 1.9; 0.0; 0.0; 1.34 | — |
| SECONDARY Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) |
0; 0; 8; 0; 1; 0 | — |
| SECONDARY Parts A, B and C: Number of Serious Respiratory Events |
0; 34; 60; 6; 2; 0 | — |
| SECONDARY Part B Infantile-onset SMA: Percentage of Time on Ventilation |
5.6; 7.5 | — |
| SECONDARY Parts A, B and C: Number of Participants With Ventilator Use |
0; 9; 22; 4; 5; 8 | — |
| SECONDARY Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale |
0.2; 0.0; 0.2; -0.2; 0.0; 0.0 | — |
| SECONDARY Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods |
0; 2; 4; 0; 0; 0 | — |
| SECONDARY Part B: Change From Baseline in the PASA Scale |
-1.6; -0.6; -0.4; 0.3; -1.7; -0.2 | — |
| SECONDARY Part B: Infantile SMA-onset: Change From (Ratio to) Baseline in CSF Concentration of NF-L |
0.06; 0.05 | =0.3785 |
| SECONDARY Parts A and C: Change From Baseline in HFMSE Total Score |
-0.8; 1.8 | — |
| SECONDARY Parts A and C: Change From Baseline in RULM Total Score |
1.5; 1.2 | — |
| SECONDARY Parts A and C: Number of Participants With WHO Motor Milestones Status |
0; 3; 6; 32; 0; 2 | — |
| SECONDARY Parts A and C: Change From Baseline in ACEND Total Score |
0.6; 0.8; 0.0; -2.8; -8.0; -2.0 | — |
| SECONDARY Parts A and C: Change From Baseline in PedsQL™ Total Score |
6.1; 1.1; 3.3; 0.7; 9.9; 6.7 | — |
| SECONDARY Part C: Change From Baseline in CHOP-INTEND Total Score |
0.0 | — |
| SECONDARY Part C: Change From Baseline in HINE Section 2 Motor Milestones Total Score |
2.0 | — |
Summary
The primary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (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 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).
Eligibility 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 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 gene (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Part B:
- Treatment with an investigational drug including but not limited to 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
- Concomitant or previous administration of any SMN2-splicing modifier (excluding nusinersen) or gene therapy, either in a clinical study or as part of medical care.
- Concurrent or previous participation in any interventional investigational study for any other drug or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT04089566). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.