An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy
CompletedPhase 1, PHASE2Results postedLast updated 13 April 2021
What this trial tests
Phase 1, PHASE2 trial testing Nusinersen in Spinal Muscular Atrophy in 34 participants. Completed in 31 January 2015.
Adults 2 to 15, any sex, with Spinal Muscular Atrophy. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuations Due to AEs, and Highest Severity of AEsPrimary· Participants were followed for the duration of the study; mean (SD) duration of treatment was 82.9 (15.4) days
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of the investigational drug product, whether or not the AE is considered related to the investigational drug product. An SAE is any AE that, in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congen
Any AE
Group
Value
95% CI
Nusinersen 3 mg
8
Nusinersen 6 mg
6
Nusinersen 9 mg
9
Nusinersen 12 mg
9
Any drug-related AE
Group
Value
95% CI
Nusinersen 3 mg
0
Nusinersen 6 mg
0
Nusinersen 9 mg
0
Nusinersen 12 mg
0
Any SAE
Group
Value
95% CI
Nusinersen 3 mg
2
Nusinersen 6 mg
0
Nusinersen 9 mg
0
Nusinersen 12 mg
1
Discontinued due to an AE
Group
Value
95% CI
Nusinersen 3 mg
0
Nusinersen 6 mg
0
Nusinersen 9 mg
0
Nusinersen 12 mg
0
Highest severity of AE=mild
Group
Value
95% CI
Nusinersen 3 mg
2
Nusinersen 6 mg
2
Nusinersen 9 mg
6
Nusinersen 12 mg
5
Highest severity of AE=moderate
Group
Value
95% CI
Nusinersen 3 mg
4
Nusinersen 6 mg
2
Nusinersen 9 mg
3
Nusinersen 12 mg
4
Highest severity of AE=severe
Group
Value
95% CI
Nusinersen 3 mg
2
Nusinersen 6 mg
2
Nusinersen 9 mg
0
Nusinersen 12 mg
0
Plasma Pharmacokinetics: Maximal Observed Plasma Drug Concentration (Cmax)Secondary· Day 1 and Day 85
Day 1
Group
Value
95% CI
Nusinersen 3 mg
51.5
± 72.7
Nusinersen 6 mg
79.8
± 57.2
Nusinersen 9 mg
141.0
± 52.8
Nusinersen 12 mg
208.0
± 110.0
Day 85
Group
Value
95% CI
Nusinersen 3 mg
32.5
± 32.3
Nusinersen 6 mg
52.8
± 33.5
Nusinersen 9 mg
127.0
± 37.7
Nusinersen 12 mg
132.0
± 85.6
Plasma Pharmacokinetics: Time to Reach Cmax in PlasmaSecondary· Day 1 and Day 85
Day 1
Group
Value
95% CI
Nusinersen 3 mg
5.09
2.03 – 12.0
Nusinersen 6 mg
5.93
2.00 – 23.0
Nusinersen 9 mg
3.92
2.00 – 8.03
Nusinersen 12 mg
4.05
1.97 – 12.0
Day 85
Group
Value
95% CI
Nusinersen 3 mg
6.08
4.12 – 6.17
Nusinersen 6 mg
6.04
5.97 – 6.25
Nusinersen 9 mg
4.12
2.00 – 6.25
Nusinersen 12 mg
5.92
1.95 – 6.07
Plasma Pharmacokinetics: Plasma Pharmacokinetics: Area Under the Plasma Concentration Time Curve From the Time of the IT Dose to 6 Hours After Dosing (AUC0-6hr)Secondary· Day 1 and Day 85
Day 1
Group
Value
95% CI
Nusinersen 3 mg
181
± 225
Nusinersen 6 mg
306
± 259
Nusinersen 9 mg
601
± 249
Nusinersen 12 mg
823
± 442
Day 85
Group
Value
95% CI
Nusinersen 3 mg
110
± 107
Nusinersen 6 mg
179
± 135
Nusinersen 9 mg
524
± 185
Nusinersen 12 mg
555
± 398
Cerebrospinal Fluid (CSF) Pharmacokinetics: Predose CSF Drug ConcentrationsSecondary· Day 1, Day 29, and Day 85
Day 1
Group
Value
95% CI
Nusinersen 3 mg
0.0651
± 0.117
Nusinersen 6 mg
0.0560
± 0.104
Nusinersen 9 mg
NA
± NA
Nusinersen 12 mg
NA
± NA
Day 29
Group
Value
95% CI
Nusinersen 3 mg
1.41
± 0.456
Nusinersen 6 mg
2.65
± 1.44
Nusinersen 12 mg
2.22
± 0.924
Day 85
Group
Value
95% CI
Nusinersen 3 mg
2.12
± 0.573
Nusinersen 6 mg
3.76
± 2.05
Nusinersen 9 mg
1.50
± 0.447
Nusinersen 12 mg
3.36
± 1.04
Urine Pharmacokinetics: Renal Clearance, Cohort 4Secondary· Day 1 and Day 85
Renal clearance of nusinersen for participants was assessed in the 12 mg reporting group only, per protocol.
Day 1
Group
Value
95% CI
Nusinersen 12 mg
0.674
± 0.602
Day 85
Group
Value
95% CI
Nusinersen 12 mg
77.5
± 92.5
Adverse events — posted to ClinicalTrials.gov
Time frame: Participants were followed for the duration of the study; mean (SD) duration of treatment was 82.9 (15.4) days..
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
This study will test the safety, tolerability, and pharmacokinetics of escalating doses of nusinersen (ISIS 396443) administered into the spinal fluid either two or three times over the duration of the trial, in participants with spinal muscular atrophy (SMA).
Four dose levels will be evaluated sequentially. Each dose level will be studied in a cohort of approximately 8 participants, where all participants will receive active drug.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06555419 — A Study to Find Out How Nusinersen is Processed in the Body When Given Through the ThecaFlex DRx™ System in Adult and Pe
· Phase 1
· recruiting
NCT04576494 — Study of the Functional Effects of Nusinersen in 5q-spinal Muscular Amyotrophy Adults (SMA Type 2 or 3 Forms)
· NA
· completed
NCT05067790 — A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spina
· Phase 3
· active not recruiting
NCT05187260 — Antisense Oligonucleotide for Spinal Muscular Atrophy
· unknown
NCT04729907 — A Study to Learn About the Long-Term Safety of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants
· Phase 3
· active not recruiting
Other recruiting trials for Spinal Muscular Atrophy
Currently open trials in the same condition.
NCT07478172 — Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
· NA
· recruiting
NCT06955897 — Characterizing Perceived Physical Fatigability in Nusinersen-treated SMA
· recruiting
NCT06396325 — A Registry Based Randomized-Controlled Trial of an Upper Limb Exergaming Intervention for Children and Adolescents With
· NA
· recruiting
NCT06288230 — An Open Label Study of Gene Therapy Product (Vesemnogene Lantuparvovec) in Spinal Muscular Atrophy
· Phase 1, PHASE2
· recruiting
NCT06321965 — Characterization of New Phenotypes of Patients With Spinal Muscular Atrophy Treated With SMN Restoring Therapy
· NA
· recruiting
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Trials by the same sponsor.
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NCT07444450 — A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy
· Phase 3
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NCT07444489 — A Study to Learn More About the Long-Term Safety and Effects of Felzartamab Infusions in Adults With Kidney Transplants
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NCT07444476 — A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years Wit
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Biogen
Last refreshed: 13 April 2021
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01703988.