Phase 2
Completed N=25
A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
Source: ClinicalTrials.gov NCT02386553 ↗Enrolled (actual)
25
Serious AEs
56.0%
Results posted
Oct 2025
Primary outcomePrimary: Time to Death or Respiratory Intervention — NA months
Summary
The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Death or Respiratory Intervention |
NA | — |
| SECONDARY Proportion of Participants Developing Clinically Manifested Spinal Muscular Atrophy (SMA) |
0.67; 0.20; 0.47; 0 | — |
| SECONDARY Percentage of Participants Alive |
100; 100 | — |
| SECONDARY Percentage of Participants Who Attained Motor Milestones Assessed as Part of the Hammersmith Infant Neurological Examination (HINE) |
100; 100; 93; 100; 73; 100 | — |
| SECONDARY Percentage of Participants Who Attained Motor Milestones as Assessed by World Health Organization (WHO) Criteria |
100; 100; 93; 100; 100; 100 | — |
| SECONDARY Change From Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale |
47.0; 51.9; 29.0 | — |
| SECONDARY Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) |
34.5; 46.4; 23.5; 22.5 | — |
| SECONDARY Change From Baseline in Weight for Age |
44.04; 34.76; -1.46; 24.49 | — |
| SECONDARY Change From Baseline in Weight for Length |
21.63; 45.26; 38.94 | — |
| SECONDARY Change From Baseline in Head Circumference |
35.59; 36.11; 19.00 | — |
| SECONDARY Change From Baseline in Chest Circumference |
34.43; 35.25; 28.20 | — |
| SECONDARY Change From Baseline in Head to Chest Circumference Ratio |
1.036; 1.027; -0.186 | — |
| SECONDARY Change From Baseline in Arm Circumference |
10.85; 10.77; 9.40 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
15; 10; 10; 4 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) |
10; 5; 3; 4; 7; 7 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) |
14; 10; 2; 1; 0; 0 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters) |
3; 1; 6; 5; 0; 1 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Coagulation Parameters [Activated Partial Thromboplastin Time (aPTT)] |
4; 2 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Coagulation Parameters [Prothrombin Time (PT)] |
7; 5 | — |
| SECONDARY Number of Participants With Shifts From Baseline in Coagulation Parameters [International Normalized Ratio (INR)] |
4; 4 | — |
| SECONDARY Percentage of Participants With Clinically Significant Shifts in Electrocardiograms (ECG) Abnormalities |
0; 0 | — |
| SECONDARY Change From Baseline in Vital Signs (Temperature) |
36.7; 36.8; 0.0; -0.1 | — |
| SECONDARY Change From Baseline in Vital Signs (Blood Pressure) |
83.4; 88.1; 22.9; 13.6; 51.1; 50.8 | — |
| SECONDARY Change From Baseline in Vital Signs (Heart Rate) |
141.5; 154.2; -47.2; -62.4 | — |
| SECONDARY Change From Baseline in Vital Signs (Respiratory Rate) |
42.1; 39.8; -21.0; -20.6 | — |
| SECONDARY Number of Participants With Neurological Examination Abnormalities Reported as AEs |
8; 1; 7; 1; 8; 0 | — |
| SECONDARY Cerebrospinal Fluid (CSF) Concentration of Nusinersen |
0.03; 0.03; 7.52; 10.22; 23.41; 24.56 | — |
| SECONDARY Plasma Concentration of Nusinersen |
391.66; 406.69; 1.60; 1.56; 0.73; 0.81 | — |
Eligibility Criteria
Key Inclusion Criteria
- Age ≤ 6 weeks at first dose.
- Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
- Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
- Ulnar compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
- Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
- Meet additional study related criteria.
Key Exclusion Criteria
- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
- Any clinical signs or symptoms at Screening or immediately prior to the first dosing (Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.
- Clinically significant abnormalities in hematology or clinical chemistry parameters.
- Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
- Meet additional study related criteria.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02386553). 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. Informational only — not medical advice.