Phase 3
N=292
A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
Spinal Muscular Atrophy
Bottom Line
View on ClinicalTrials.gov: NCT02594124 ↗Enrolled (actual)
292
Serious AEs
67.8%
Results posted
Oct 2024
Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — 13; 24; 65; 12 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- nusinersen (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Biogen
- Primary completion
- Aug 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
13; 24; 65; 12; 20; 25 | — |
| PRIMARY Number of Participants With Vital Sign Abnormalities Reported as AEs |
1; 0; 6; 1; 0; 0 | — |
| PRIMARY Number of Participants With Weight Abnormalities Reported as AEs |
0; 0; 3; 1; 0; 1 | — |
| PRIMARY Number of Participants With Neurological Abnormalities Reported as AEs |
2; 0; 1; 0; 1; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities Reported as AEs |
1; 0; 6; 1; 2; 0 | — |
| PRIMARY Number of Participants With Coagulation Parameters Reported as AEs |
1; 0; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Shifts in12 Lead Electrocardiogram (ECG) Results |
2; 1; 6; 1; 0; 0 | — |
| PRIMARY Number of Participants Taking Any Concomitant Medication |
13; 24; 65; 12; 20; 25 | — |
| SECONDARY Mean Number of New Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria |
0.4; 0.0; 0.7; 0.0; -0.6; -0.1 | — |
| SECONDARY Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) |
13; 86; 34; 13; 9; 18 | — |
| SECONDARY Number of Participants Who Died or Met Permanent Ventilation |
0; 6; 11; 1; 0; 1 | — |
| SECONDARY Number of Participants Not Requiring Permanent Ventilation |
13; 20; 61; 11; 20; 42 | — |
| SECONDARY Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale |
47.4; 17.3; 38.8; -6.0; 11.5; 4.7 | — |
| SECONDARY Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score |
14.5; 0.0; 7.3; 6.8; 25.6; 53.6 | — |
| SECONDARY Change From Baseline in Revised Upper Limb Module (RULM) Total Score |
11.8; 1.7; 10.3; 7.6; 24.1; 35.9 | — |
| SECONDARY Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT) |
0; 253.3; 156.5; 91.5 | — |
| SECONDARY Number of Participants Who Experienced Contracture Assesment |
9; 10; 36; 8; 13; 8 | — |
| SECONDARY Change From Baseline in Compound Muscular Action Potential (CMAP) |
3.02; 0.35; 1.91; 0.94; 1.89; 2.71 | — |
| SECONDARY Change From Baseline in Body Length |
24.2; 19.9; 29.4; 18.8; 18.8; 23.1 | — |
| SECONDARY Change From Baseline in Weight |
9.8; 7.7; 9.3; 9.5; 15.1; 13.8 | — |
| SECONDARY Change From Baseline in Weight for Age Percentile |
5.7; -5.3; 0.3; -0.7; 0.9; 20.2 | — |
| SECONDARY Percentage of CMAP Responders |
85; 0; 72; 33; 65; 67 | — |
| SECONDARY Number of Participants Who Achieved Motor Milestones |
5; 0; 16; 3; 13; 23 | — |
| SECONDARY Number of Participants Who Achieved Standing Alone and Walking With Assistance |
1; 0; 0; 0; 1; 19 | — |
| SECONDARY Total Number of Hospitalizations Due to Serious Respiratory Events |
2; 12; 30; 2; 0; 0 | — |
| SECONDARY Total Number of Hospitalizations Due to Serious Adverse Events |
6; 26; 89; 12; 2; 0 | — |
| SECONDARY Percent of Time in Hospitalization |
0.00; 1.11; 0.28; 0.28; 0.00; 0.00 | — |
| SECONDARY Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine by Visit |
22.7; 16.6; 34.8; 49.2; 38.5; 29.8 | — |
| SECONDARY Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain |
37.1; 22.4; 47.5; 32.6; 37.5; 52.7 | — |
| SECONDARY Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) Questionnaire Total Score |
14.2; 0.6; 18.5; 9.2; 2.1; 0.6 | — |
| SECONDARY Number of Participants With Disease-related Hospitalizations and AEs |
6; 9; 27; 5; 9; 0 | — |
| SECONDARY Survival Rate |
100; 79.16; 87.69; 97.61; 98.79; 100 | — |
Summary
The primary objective is to evaluate long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with Spinal Muscular Atrophy (SMA) who previously participated in investigational studies of nusinersen. The secondary objective is to examine the long-term efficacy of nusinersen administered by IT injection to participants with SMA who previously participated in investigational studies of nusinersen.
Eligibility Criteria
Key Inclusion Criteria
- Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
- Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks
Key Exclusion Criteria
- Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
- Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
- Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02594124). 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.