Trial · NCT01839656
A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
NCT01839656, Phase 2, Completed, Biogen; results first posted 2018-10-30
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA). Trials, record NCT01839656. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01839656
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
- NCT number
- NCT01839656
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 21 participants, actual
- Lead sponsor
- Biogen
- Conditions
- Spinal Muscular Atrophy
- Interventions
- nusinersen
- First posted
- 2013-04-25
- Last updated
- 2021-02-17
- Other registries' IDs
- eudract:2017-000621-12
- Results first posted
- 2018-10-30
Source ClinicalTrials.gov
Registered outcomes9
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | Day 1352 or Early Termination | Section 2 of HINE consists of 8 independent milestone categories. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. Overall, there are a total of 26 milestones that can be achieved across the 8 categories. Improvement was defined as any of the following: 1. An increase from baseline of 2 milestones or more, or the achievement of pincer grasp in the voluntary grasp category 2. An increase from baseline of 2 milestones or more, or achievement of touching toes in the ability to kick category 3. An increase from baseline of 1 milestone or more in any of the remaining 6 categories: head control, rolling, sitting, crawling, standing, or walking. |
| Secondary | Event-free Survival at the End of Study | Up to Day 1638 | Event-free survival was defined as the percent of participants who were alive and did not require permanent ventilatory support (defined as tracheostomy or the need for ≥16 hours ventilation/day continuously for at least 2 weeks in the absence of an acute reversible illness) Event-free survival was estimated using Kaplan-Meier methodology. |
| Secondary | Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | Day 1352 or Early Termination | The CHOP-INTEND test includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0 (worst) to 4 (best). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Improvement was defined as an increase in total CHOP INTEND score ≥4 points from baseline as of the last study visit. |
| Secondary | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Baseline, Day 1072 | CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A positive change from Baseline indicates that the number of motor neurons increased. |
| Secondary | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Up to Day 1352 | AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient 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 congenital anomaly or birth defect in the offspring of the subject (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor. |
| Secondary | Concentration of Nusinersen in Cerebrospinal Fluid (CSF) | Day 1135 (Predose) | The concentration of nusinersen in CSF was measured by using standard laboratory assays. |
| Secondary | PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | Cmax is the maximum observed concentration of study drug in plasma. |
| Secondary | PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | Tmax is the time at which Cmax occurs. |
| Secondary | PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | AUC is area under the plasma concentration-time curve from zero time (Predose) to 4 hours after IT administration of study drug. AUC was determined by using the linear trapezoidal rule. |
Source ClinicalTrials.gov
Outcomes9
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | Day 1352 or Early Termination | Safety Population: All participants who were registered and received at least 1 dose of nusinersen. | Percent of participants | NUMBER |
| SECONDARY | Event-free Survival at the End of Study | Up to Day 1638 | Safety Population: All participants who were registered and received at least 1 dose of nusinersen. | Percent of participants | NUMBER |
| SECONDARY | Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | Day 1352 or Early Termination | Safety Population: All participants who were registered and received at least 1 dose of nusinersen. | Percent of participants | NUMBER |
| SECONDARY | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Baseline, Day 1072 | Safety Population: All participants who were registered and received at least 1 dose of nusinersen. Here, number of participants analyzed is the participants who were evaluable for this outcome measure. | mV | MEAN |
| SECONDARY | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Up to Day 1352 | Safety Population: All participants who were registered and received at least 1 dose of nusinersen. | participants | NUMBER |
| SECONDARY | Concentration of Nusinersen in Cerebrospinal Fluid (CSF) | Day 1135 (Predose) | PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample. Here, number of participants analyzed is the participants who were evaluable for this outcome measure. | nanograms/milliliter (ng/mL) | MEAN |
| SECONDARY | PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample. | ng/mL | MEAN |
| SECONDARY | PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample. | hr | MEAN |
| SECONDARY | PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample. | ng x hr/mL | MEAN |
Source ClinicalTrials.gov
Results by group22
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | Nusinersen 6 mg | 25.0 | Percent of participants | ||
| Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | Nusinersen 12 mg | 68.8 | Percent of participants | ||
| Event-free Survival at the End of Study | Nusinersen 6 mg | 25.0 | Percent of participants | ||
| Event-free Survival at the End of Study | Nusinersen 12 mg | 62.5 | Percent of participants | ||
| Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | Nusinersen 6 mg | 25.0 | Percent of participants | ||
| Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | Nusinersen 12 mg | 62.5 | Percent of participants | ||
| Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Nusinersen 6 mg | Peroneal nerve | 1.88 | Standard Deviation 2.58 | mV |
| Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Nusinersen 12 mg | Peroneal nerve | 2.81 | Standard Deviation 1.28 | mV |
| Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Nusinersen 6 mg | Ulnar nerve | 0.776 | Standard Deviation 1.448 | mV |
| Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Nusinersen 12 mg | Ulnar nerve | 0.685 | Standard Deviation 0.415 | mV |
1 to 10 of 22Source ClinicalTrials.gov
See all 22 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Nusinersen 6 mg | 5 | |
| Overall Study | STARTED | Nusinersen 12 mg | 16 | |
| Overall Study | Completed Loading Dose Period | Nusinersen 6 mg | 4 | |
| Overall Study | Completed Loading Dose Period | Nusinersen 12 mg | 15 | |
| Overall Study | COMPLETED | Nusinersen 6 mg | 2 | |
| Overall Study | COMPLETED | Nusinersen 12 mg | 0 | |
| Overall Study | NOT COMPLETED | Nusinersen 6 mg | 3 | |
| Overall Study | NOT COMPLETED | Nusinersen 12 mg | 16 |
Source ClinicalTrials.gov
Adverse events560
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Nusinersen 6 mg | 0 | 4 | |
| other | Anaemia | Blood and lymphatic system disorders | Nusinersen 12 mg | 2 | 16 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Nusinersen 6 mg | 0 | 4 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Nusinersen 12 mg | 1 | 16 | |
| other | Lymphadenopathy | Blood and lymphatic system disorders | Nusinersen 6 mg | 1 | 4 | |
| other | Lymphadenopathy | Blood and lymphatic system disorders | Nusinersen 12 mg | 1 | 16 | |
| other | Neutropenia | Blood and lymphatic system disorders | Nusinersen 6 mg | 0 | 4 | |
| other | Neutropenia | Blood and lymphatic system disorders | Nusinersen 12 mg | 1 | 16 | |
| other | Thrombocytosis | Blood and lymphatic system disorders | Nusinersen 6 mg | 0 | 4 | |
| other | Thrombocytosis | Blood and lymphatic system disorders | Nusinersen 12 mg | 1 | 16 |
1 to 10 of 560Source ClinicalTrials.gov
See all 560 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Nusinersen 6 mg | 1 | 4 |
| Total, all-cause mortality | Nusinersen 12 mg | 4 | 16 |
| Total, other adverse events | Nusinersen 6 mg | 4 | 4 |
| Total, other adverse events | Nusinersen 12 mg | 16 | 16 |
| Total, serious adverse events | Nusinersen 6 mg | 3 | 4 |
| Total, serious adverse events | Nusinersen 12 mg | 13 | 16 |
Source ClinicalTrials.gov
Papers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Nusinersen 6 mg vs Nusinersen 12 mg: deaths from any cause | Trial comparisons |
| Nusinersen 6 mg vs Nusinersen 12 mg: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01839656
GET https://conductscience.org/api/trials/v1/NCT01839656/results?page=2