NCT02594124 (SHINE) is a Phase 3 clinical trial of nusinersen in Spinal Muscular Atrophy, sponsored by Biogen.

Who is sponsoring NCT02594124?

NCT02594124 is sponsored by Biogen.

What drugs are being tested in NCT02594124?

Interventions in NCT02594124: nusinersen.

What condition does NCT02594124 study?

NCT02594124 studies Spinal Muscular Atrophy.

Is NCT02594124 still recruiting?

NCT02594124 is currently completed. Last updated 22 October 2024.

Are results published for NCT02594124?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2024-10-22 · How we verify

NCT02594124: SHINE

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies

Completed Phase 3 Results posted Last updated 22 October 2024

What this trial tests

Phase 3 trial testing nusinersen in Spinal Muscular Atrophy in 292 participants. Completed in 21 August 2023.

Timeline

4 November 2015

Primary endpoint
21 August 2023

21 August 2023

Quick facts

Lead sponsor	Biogen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	292
Start date	4 November 2015
Primary completion	21 August 2023
Estimated completion	21 August 2023
Sites	47 locations across France, Hong Kong, Italy, Japan, Belgium, Sweden, United Kingdom, Germany

Drugs / interventions tested

nusinersen (NUSINERSEN) — full drug profile →

Conditions studied

Spinal Muscular Atrophy — all drugs for Spinal Muscular Atrophy →

Sponsor

Biogen — full company profile →

Who can join

Eligibility, 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 Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · From Day 1 up to the end of the study (up to 2848 days)

AE:unfavorable and unintended sign, symptom, or disease temporally associated with study/use of an investigational drug, whether or not it's considered related to investigational drug. SAE:AE that in view of either Investigator/Sponsor, meets any of the following criteria: results in death;is life-threatening:i.e.poses risk of death, hospitalization/it's prolongation;results in a persistent or significant incapacity or substantial disruption of normal life functions;results in congenital anomaly or birth defect in offspring;is an important event in the opinion of Investigator/Sponsor. TEAE: if

AEs

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	24
Infantile SMA Onset CS3B Previous ISIS 396443	65
Infantile SMA Onset 232SM202	12
Later SMA Onset CS12 Type 2	20
Later SMA Onset CS12 Type 3	25
Later SMA Onset CS4 Previous Control	42
Later SMA Onset CS4 Previous ISIS 396443	80
Later SMA Onset 232SM202	8

SAEs

Group	Value	95% CI
Infantile SMA Onset CS3A	11
Infantile SMA Onset CS3B Previous Control	23
Infantile SMA Onset CS3B Previous ISIS 396443	59
Infantile SMA Onset 232SM202	9
Later SMA Onset CS12 Type 2	12
Later SMA Onset CS12 Type 3	6
Later SMA Onset CS4 Previous Control	26
Later SMA Onset CS4 Previous ISIS 396443	47
Later SMA Onset 232SM202	5

Number of Participants With Vital Sign Abnormalities Reported as AEs Primary · From Day 1 up to the end of the study (up to 2848 days)

The vital sign assessments included blood pressure, temperature, pulse rate, and respiratory rate. Participants with abnormalities in these assessments recorded as AEs were reported.

Bradycardia

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	6
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Tachycardia

Group	Value	95% CI
Infantile SMA Onset CS3A	2
Infantile SMA Onset CS3B Previous Control	4
Infantile SMA Onset CS3B Previous ISIS 396443	5
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	2
Later SMA Onset 232SM202	0

Pyrexia

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	15
Infantile SMA Onset CS3B Previous ISIS 396443	50
Infantile SMA Onset 232SM202	5
Later SMA Onset CS12 Type 2	10
Later SMA Onset CS12 Type 3	3
Later SMA Onset CS4 Previous Control	21
Later SMA Onset CS4 Previous ISIS 396443	39
Later SMA Onset 232SM202	5

Body Temperature Increased

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	1
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Heart Rate Increased

Group	Value	95% CI
Infantile SMA Onset CS3A	3
Infantile SMA Onset CS3B Previous Control	2
Infantile SMA Onset CS3B Previous ISIS 396443	4
Infantile SMA Onset 232SM202	3
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	2
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Oxygen Saturation Decreased

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	9
Infantile SMA Onset CS3B Previous ISIS 396443	20
Infantile SMA Onset 232SM202	2
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	1
Later SMA Onset CS4 Previous Control	2
Later SMA Onset CS4 Previous ISIS 396443	3
Later SMA Onset 232SM202	0

Respiratory Rate Increased

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Tachypnoea

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Number of Participants With Weight Abnormalities Reported as AEs Primary · From Day 1 up to the end of the study (up to 2848 days)

Weight decrease was characterized by a decrease of \>=7% from baseline and weight increase was characterized by an increase of \>=7% from baseline. Participants with these abnormalities recorded as AEs were reported.

Weight Decreased

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	3
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	1
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	3
Later SMA Onset 232SM202	0

Weight Increased

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	5
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Number of Participants With Neurological Abnormalities Reported as AEs Primary · From Day 1 up to the end of the study (up to 2848 days)

Participants with abnormalities in neurological examinations recorded as AEs were reported.

Areflexia

Group	Value	95% CI
Infantile SMA Onset CS3A	2
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	1
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0

Hyporeflexia

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Nystagmus

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	4
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Motor Dysfunction

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Muscle Contractions Involuntary

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	2
Later SMA Onset CS12 Type 3	1
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	4
Later SMA Onset 232SM202	0

Myoclonus

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	1
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Paraesthesia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	1
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	1

Tremor

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	1
Later SMA Onset CS12 Type 3	1
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	3
Later SMA Onset 232SM202	0

Number of Participants With Laboratory Abnormalities Reported as AEs Primary · From Day 1 up to the end of the study (up to 2848 days)

Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs were reported.

Anaemia

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	6
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	2
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	1

Leukocytosis

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	3
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	2
Later SMA Onset 232SM202	0

Leukopenia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	1
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0

Lymphopenia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0

Neutropenia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	2
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Neutrophilia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	2
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	2
Later SMA Onset 232SM202	0

Pancytopenia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	0
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0

Thrombocytopenia

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Number of Participants With Coagulation Parameters Reported as AEs Primary · From Day 1 up to the end of the study (up to 2848 days)

Coagulation parameters included activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Participants with abnormalities in these coagulation parameters recorded as AEs were reported.

Activated Partial Thromboplastin Time Prolonged

Group	Value	95% CI
Infantile SMA Onset CS3A	1
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	2
Later SMA Onset 232SM202	0

International Normalised Ratio Abnormal

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

International Normalised Ratio Decreased

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Coagulopathy

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	1
Infantile SMA Onset 232SM202	0
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	0
Later SMA Onset CS4 Previous ISIS 396443	0
Later SMA Onset 232SM202	0

Number of Participants With Clinically Significant Shifts in12 Lead Electrocardiogram (ECG) Results Primary · From Day 1 up to the end of the study (up to 2848 days)

Clinical significance of abnormalities in 12 lead ECG was determined based on the investigator's discretion.

Group	Value	95% CI
Infantile SMA Onset CS3A	2
Infantile SMA Onset CS3B Previous Control	1
Infantile SMA Onset CS3B Previous ISIS 396443	6
Infantile SMA Onset 232SM202	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS12 Type 3	0
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0

Number of Participants Taking Any Concomitant Medication Primary · From Day 1 up to the end of the study (up to 2848 days)

A concomitant therapy is any non-protocol-specified drug or substance (including over-the-counter medications, herbal medications, and vitamin supplements) administered between the beginning of screening and the last telephone contact or study visit.

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	24
Infantile SMA Onset CS3B Previous ISIS 396443	65
Infantile SMA Onset 232SM202	12
Later SMA Onset CS12 Type 2	20
Later SMA Onset CS12 Type 3	25
Later SMA Onset CS4 Previous Control	42
Later SMA Onset CS4 Previous ISIS 396443	83
Later SMA Onset 232SM202	8

Mean Number of New Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria Secondary · MMDR Period: At Day 1800

The WHO motor milestones are a set of six milestones in motor development, all of which would be expected to be attained by 24 months of age in healthy children. The individual milestones are: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. Mean of number of new milestones achieved was calculated and reported in this outcome measure.

Group	Value	95% CI
Infantile SMA Onset CS3A	0.4	± 0.73
Infantile SMA Onset CS3B Previous Control	0.0	± 0.00
Infantile SMA Onset CS3B Previous ISIS 396443	0.7	± 1.15
Infantile SMA Onset 232SM202	0.0	± 0.53
Later SMA Onset CS12 Type 2	-0.6	± 0.79
Later SMA Onset CS12 Type 3	-0.1	± 0.73
Later SMA Onset CS4 Previous Control	-0.1	± 0.32
Later SMA Onset CS4 Previous ISIS 396443	-0.2	± 0.60
Later SMA Onset 232SM202	-0.2	± 0.75

Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) Secondary · At Day 309

HINE is evaluated in infants between 2-24 months of age. It's a simple, standardized instrument including 26 items assessing different aspects of neurological examinations, such as cranial nerves, posture, movements, tone, and reflexes. In this study, Module 2 of HINE (HINE-2) was assessed, which evaluates 8 developmental milestones (head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking) scored on a 3, 4, or 5-point scale, with 0 indicating inability to perform task and score of 2, 3, or 4 indicating full milestone development. Total score is calcula

Head Control: Unable to Maintain Head Upright

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	86
Infantile SMA Onset CS3B Previous ISIS 396443	34

Head Control: Wobbles

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	9
Infantile SMA Onset CS3B Previous ISIS 396443	18

Head Control: All the Time Maintained Upright

Group	Value	95% CI
Infantile SMA Onset CS3A	75
Infantile SMA Onset CS3B Previous Control	5
Infantile SMA Onset CS3B Previous ISIS 396443	48

Sitting: Cannot Sit

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	100
Infantile SMA Onset CS3B Previous ISIS 396443	39

Sits With Support at Hips

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	19

Sitting: Props

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	8

Sitting: Stable sit

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	19

Sitting: Pivots (rotates)

Group	Value	95% CI
Infantile SMA Onset CS3A	63
Infantile SMA Onset CS3B Previous Control	0
Infantile SMA Onset CS3B Previous ISIS 396443	15

Number of Participants Who Died or Met Permanent Ventilation Secondary · MMDR Period: Up to Day 1800

Permanent ventilation was defined as tracheostomy or \>=16 hours of ventilator support per day continuously for \>21 days in the absence of an acute reversible event.

Group	Value	95% CI
Infantile SMA Onset CS3A	0
Infantile SMA Onset CS3B Previous Control	6
Infantile SMA Onset CS3B Previous ISIS 396443	11
Later SMA Onset CS4 Previous Control	1
Later SMA Onset CS12 Type 2	0
Later SMA Onset CS4 Previous ISIS 396443	1
Later SMA Onset 232SM202	0
Infantile SMA Onset 232SM202	2
Later SMA Onset CS12 Type 3	0

Number of Participants Not Requiring Permanent Ventilation Secondary · MMDR Period: Up to Day 1800

Permanent ventilation was defined as tracheostomy or \>=16 hours of ventilator support per day continuously for \>21 days in the absence of an acute reversible event.

Group	Value	95% CI
Infantile SMA Onset CS3A	13
Infantile SMA Onset CS3B Previous Control	20
Infantile SMA Onset CS3B Previous ISIS 396443	61
Infantile SMA Onset 232SM202	11
Later SMA Onset CS12 Type 2	20
Later SMA Onset CS4 Previous Control	42
Later SMA Onset CS4 Previous ISIS 396443	83
Later SMA Onset CS12 Type 3	25
Later SMA Onset 232SM202	8

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 up to the end of the study (up to 2848 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Infantile SMA Onset CS3A

Serious: 11/13 (85%)

Deaths: 0/13

Infantile SMA Onset CS3B Previous Control

Serious: 23/24 (96%)

Deaths: 5/24

Infantile SMA Onset CS3B Previous ISIS 396443

Serious: 59/65 (91%)

Deaths: 8/65

Infantile SMA Onset 232SM202

Serious: 9/12 (75%)

Deaths: 1/12

Later SMA Onset 232SM202

Serious: 5/8 (63%)

Deaths: 0/8

Later SMA Onset CS12 Type 2

Serious: 12/20 (60%)

Deaths: 0/20

Later SMA Onset CS12 Type 3

Serious: 6/25 (24%)

Deaths: 0/25

Later SMA Onset CS4 Previous Control

Serious: 26/42 (62%)

Deaths: 1/42

Later SMA Onset CS4 Previous ISIS 396443

Serious: 47/83 (57%)

Deaths: 1/83

Serious adverse events (221 terms)

Reaction	System	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B P…	Infantile SMA Onset CS3B P…	Infantile SMA Onset 232SM202	Later SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previo…	Later SMA Onset CS4 Previo…
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—
Scoliosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Respiratory syncytial virus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Respiratory distress	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Enterovirus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Parainfluenzae virus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumonia aspiration	Infections and infestations	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Rhinovirus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Atelectasis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—	—
Metapneumovirus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumonia bacterial	Infections and infestations	—	—	—	—	—	—	—	—	—
Respiratory syncytial virus bronchiolitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Post lumbar puncture syndrome	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Oxygen saturation decreased	Investigations	—	—	—	—	—	—	—	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Kyphoscoliosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—	—	—	—	—

Other adverse events (353 terms — click to expand)

Reaction	System	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B P…	Infantile SMA Onset CS3B P…	Infantile SMA Onset 232SM202	Later SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previo…	Later SMA Onset CS4 Previo…
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—
Scoliosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Muscle contracture	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Ear infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Post lumbar puncture syndrome	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Joint contracture	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—
Oxygen saturation decreased	Investigations	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Covid-19	Infections and infestations	—	—	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Otitis media	Infections and infestations	—	—	—	—	—	—	—	—	—
Rhinovirus infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—	—
Pseudomonas infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Salivary hypersecretion	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Viral infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Kyphosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Teething	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Seasonal allergy	Immune system disorders	—	—	—	—	—	—	—	—	—
Hip deformity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Osteopenia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Atelectasis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Scoliosis, Acute respiratory failure, Respiratory syncytial virus infection, Respiratory distress, Respiratory failure, Respiratory tract infection, Lower respiratory tract infection.

Data from ClinicalTrials.gov NCT02594124 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Splice-switching antisense oligonucleotides as therapeutic drugs.
Havens MA, Hastings ML. · · 2016 · cited 402× · PMID 27288447 · DOI 10.1093/nar/gkw533
Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, et al · · 2019 · cited 206× · PMID 31019106 · DOI 10.1212/wnl.0000000000007527
Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives.
Dangouloff T, Servais L. · · 2019 · cited 149× · PMID 31632042 · DOI 10.2147/tcrm.s172291
Gene-based therapies for neurodegenerative diseases.
Sun J, Roy S. · · 2021 · cited 126× · PMID 33526943 · DOI 10.1038/s41593-020-00778-1
Antisense oligonucleotides in neurological disorders.
Wurster CD, Ludolph AC. · · 2018 · cited 100× · PMID 29854003 · DOI 10.1177/1756286418776932
Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study.
Acsadi G, Crawford TO, Müller-Felber W, Shieh PB, et al · · 2021 · cited 88× · PMID 33501671 · DOI 10.1002/mus.27187
New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges.
Messina S, Sframeli M. · · 2020 · cited 86× · PMID 32668756 · DOI 10.3390/jcm9072222
Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology.
Weng Y, Huang Q, Li C, Yang Y, et al · · 2020 · cited 72× · PMID 31927331 · DOI 10.1016/j.omtn.2019.12.004

Verify or expand the search:

Other trials of nusinersen

Trials testing the same drug.

NCT03878030 — Effect of Nusinersen on Adults With Spinal Muscular Atrophy · completed
NCT04591678 — Adults With SMA Treated With Nusinersen · completed
NCT02193074 — A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy · Phase 3 · terminated
NCT02052791 — An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SM · Phase 1 · completed
NCT01839656 — A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular · Phase 2 · completed

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

Other Biogen trials

Trials by the same sponsor.

NCT07483632 — A Study to Learn About the Safety of Diroximel Fumarate (DRF) and Dimethyl Fumarate (DMF) and Their Effects on Relapses · Phase 3 · not yet recruiting
NCT06628687 — A Study to Learn How BIIB141 (Omaveloxolone) Affects the Health of Participants With Friedrich's Ataxia Who Took it Duri · recruiting
NCT07444450 — A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy · Phase 3 · not yet recruiting
NCT07444489 — A Study to Learn More About the Long-Term Safety and Effects of Felzartamab Infusions in Adults With Kidney Transplants · Phase 3 · not yet recruiting
NCT07444476 — A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years Wit · Phase 3 · not yet recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02594124 (US National Library of Medicine, public domain)
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: 22 October 2024

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/NCT02594124.

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