Trial · NCT02292537
A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA)
NCT02292537, Phase 3, Completed, Biogen; results first posted 2018-02-22
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA). Trials, record NCT02292537. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02292537
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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 and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA)
- NCT number
- NCT02292537
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 126 participants, actual
- Lead sponsor
- Biogen
- Conditions
- Spinal Muscular Atrophy
- Interventions
- Nusinersen, Sham procedure
- First posted
- 2014-11-17
- Last updated
- 2021-02-17
- Other registries' IDs
- eudract:2014-001947-18
- Results first posted
- 2018-02-22
- Limitations and caveats
- After the interim analysis of the study, the decision was made in October 2016 to terminate the study early and participants were invited for end-of-study visits.
Source ClinicalTrials.gov
Registered outcomes15
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Month 15 | Baseline and Month 15 | The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. The scale was originally developed with 20 scored activities and was devised for use in children with SMA Type 2 and Type 3 with limited ambulation to give objective information on motor ability and clinical progression. The expanded scale includes an additional module of 13 items developed to allow for evaluation of ambulatory SMA patients. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. |
| Secondary | Proportion of Participants Who Achieved a 3-Point Increase From Baseline in HFMSE Score at Month 15 | Baseline and Month 15 | The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. The scale was originally developed with 20 scored activities and was devised for use in children with SMA Type 2 and Type 3 with limited ambulation to give objective information on motor ability and clinical progression. The expanded scale includes an additional module of 13 items developed to allow for evaluation of ambulatory SMA patients. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. |
| Secondary | Proportion of Participants That Achieved Any New Motor Milestone at Month 15 | Month 15 | New motor milestones are defined as sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. |
| Secondary | Number of New Motor Milestones Achieved Per Participant | Month 15 | New motor milestones are defined as sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. |
| Secondary | Change From Baseline in Revised Upper Limb Module (RULM) Test | Baseline and Month 15 | The RULM Test is used in patients with SMA to assess upper limb functional ability items that are reflective of activities of daily living (i.e., raise a can to mouth as if drinking, take a coin and place it in a box, remove the lid of a container). The RULM test has a total of 20 items with an entry item that serves as functional class identification and does not contribute to the total score. The remaining 19 scorable items reflect different functional domains and are graded on a 3-point system with a score of 0 (unable), 1 (able, with modification), and a maximum of 2 (able, no difficulty). There is only 1 item (item I) that is scored as a can/cannot score, with 1 as the highest score. Scorable items are summed for a total score range of 0-37, with higher scores increased great upper limb function. A positive change from Baseline indicates improvement. |
| Secondary | Proportion of Participants That Achieved Standing Alone | Month 15 | If the participant was unable to achieve standing alone at Baseline but could achieve this at Month 15 then they were considered a responder. If they could not achieve this or if a participant terminated the study prior to the 15-month assessment due to treatment failure or death, then any imputed value was ignored and the participant was considered as a non-responder. |
| Secondary | Proportion of Participants That Achieved Walking With Assistance | Month 15 | If the participant was unable to achieve walking with assistance at baseline but could achieve this at Month 15 then they were considered a responder. If they could not achieve this or if a participant terminated the study prior to the 15-month assessment due to treatment failure or death, then any imputed value was ignored and the participant was considered as a non-responder. |
| Secondary | Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline through Month 15 | AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death; an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. |
| Secondary | Number of Participants With Clinically Significant Vital Sign Abnormalities | Baseline through Month 15 | Vital signs assessed for clinical significance include resting blood pressure, pulse, respiratory rate, and temperature. |
| Secondary | Number of Participants With Clinically Significant Weight Abnormalities | Baseline through Month 15 | Weight changes assessed from Baseline to Month 15. |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 registered outcomesOutcomes15
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Month 15 | Baseline and Month 15 | ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline HFMSE data were imputed using the multiple imputation method. | scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Proportion of Participants Who Achieved a 3-Point Increase From Baseline in HFMSE Score at Month 15 | Baseline and Month 15 | ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline HFMSE data were imputed using multiple imputation. | Proportion of participants | NUMBER |
| SECONDARY | Proportion of Participants That Achieved Any New Motor Milestone at Month 15 | Month 15 | Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data. | Proportion of participants | NUMBER |
| SECONDARY | Number of New Motor Milestones Achieved Per Participant | Month 15 | Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data. | milestones achieved | MEAN |
| SECONDARY | Change From Baseline in Revised Upper Limb Module (RULM) Test | Baseline and Month 15 | ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline data were imputed using multiple imputation. | scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Proportion of Participants That Achieved Standing Alone | Month 15 | Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data. | Proportion of participants | NUMBER |
| SECONDARY | Proportion of Participants That Achieved Walking With Assistance | Month 15 | Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data. | Proportion of participants | NUMBER |
| SECONDARY | Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline through Month 15 | Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. All participants with AEs were reported in this outcome measure, whereas in Adverse Event section there was at 5% reporting threshold to be met. | participants | NUMBER |
| SECONDARY | Number of Participants With Clinically Significant Vital Sign Abnormalities | Baseline through Month 15 | Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Any new or worsening vital sign findings were reported as AEs and are presented in the AE/SAE section of the results. | participants | NUMBER |
| SECONDARY | Number of Participants With Clinically Significant Weight Abnormalities | Baseline through Month 15 | Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Any new or worsening weight abnormality findings were reported as AEs and are presented in the AE/SAE section of the results. | participants | NUMBER |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 outcomesResults by group184
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Month 15 | Sham Procedure | -1.0 | 95% Confidence Interval -2.5 to 0.5 | scores on a scale | |
| Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Month 15 | Nusinersen | 3.9 | 95% Confidence Interval 3.0 to 4.9 | scores on a scale | |
| Proportion of Participants Who Achieved a 3-Point Increase From Baseline in HFMSE Score at Month 15 | Sham Procedure | 26.3 | 95% Confidence Interval 12.40 to 40.22 | Proportion of participants | |
| Proportion of Participants Who Achieved a 3-Point Increase From Baseline in HFMSE Score at Month 15 | Nusinersen | 56.8 | 95% Confidence Interval 45.62 to 68.05 | Proportion of participants | |
| Proportion of Participants That Achieved Any New Motor Milestone at Month 15 | Sham Procedure | 5.9 | 95% Confidence Interval 0.72 to 19.68 | Proportion of participants | |
| Proportion of Participants That Achieved Any New Motor Milestone at Month 15 | Nusinersen | 19.7 | 95% Confidence Interval 10.93 to 31.32 | Proportion of participants | |
| Number of New Motor Milestones Achieved Per Participant | Sham Procedure | -0.2 | Standard Deviation 0.54 | milestones achieved | |
| Number of New Motor Milestones Achieved Per Participant | Nusinersen | 0.2 | Standard Deviation 0.51 | milestones achieved | |
| Change From Baseline in Revised Upper Limb Module (RULM) Test | Sham Procedure | 0.5 | 95% Confidence Interval -0.6 to 1.6 | scores on a scale | |
| Change From Baseline in Revised Upper Limb Module (RULM) Test | Nusinersen | 4.2 | 95% Confidence Interval 3.4 to 5.0 | scores on a scale |
1 to 10 of 184Source ClinicalTrials.gov
See all 184 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Sham Procedure | 42 | |
| Overall Study | STARTED | Nusinersen | 84 | |
| Overall Study | Completed Treatment | Sham Procedure | 42 | |
| Overall Study | Completed Treatment | Nusinersen | 83 | |
| Overall Study | COMPLETED | Sham Procedure | 42 | |
| Overall Study | COMPLETED | Nusinersen | 84 | |
| Overall Study | NOT COMPLETED | Sham Procedure | 0 | |
| Overall Study | NOT COMPLETED | Nusinersen | 0 |
Source ClinicalTrials.gov
Adverse events92
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 | Constipation | Gastrointestinal disorders | Sham Procedure | 4 | 42 | |
| other | Constipation | Gastrointestinal disorders | Nusinersen | 5 | 84 | |
| other | Diarrhoea | Gastrointestinal disorders | Sham Procedure | 3 | 42 | |
| other | Diarrhoea | Gastrointestinal disorders | Nusinersen | 8 | 84 | |
| other | Vomiting | Gastrointestinal disorders | Sham Procedure | 5 | 42 | |
| other | Vomiting | Gastrointestinal disorders | Nusinersen | 24 | 84 | |
| other | Pyrexia | General disorders | Sham Procedure | 15 | 42 | |
| other | Pyrexia | General disorders | Nusinersen | 36 | 84 | |
| other | Bronchitis | Infections and infestations | Sham Procedure | 4 | 42 | |
| other | Bronchitis | Infections and infestations | Nusinersen | 7 | 84 |
1 to 10 of 92Source ClinicalTrials.gov
See all 92 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Sham Procedure | 0 | 42 |
| Total, all-cause mortality | Nusinersen | 0 | 84 |
| Total, other adverse events | Sham Procedure | 42 | 42 |
| Total, other adverse events | Nusinersen | 75 | 84 |
| Total, serious adverse events | Sham Procedure | 12 | 42 |
| Total, serious adverse events | Nusinersen | 14 | 84 |
Source ClinicalTrials.gov
Papers2
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 comparisons4
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Nusinersen vs Sham Procedure: Number of Participants With Abnormal, Clinically Relevant Post-Baseline Worsening in Electrocardiogram (ECG) in Results | Trial comparisons |
| Nusinersen vs Sham Procedure: Number of Participants Taking Any Concomitant Medication Related to Dosing Procedure or Sham Procedure | Trial comparisons |
| Nusinersen vs Sham Procedure: deaths from any cause | Trial comparisons |
| Nusinersen vs Sham Procedure: 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/NCT02292537
GET https://conductscience.org/api/trials/v1/NCT02292537/results?page=2