A Safety and Efficacy Study of Intravenous (IV) Elezanumab Assessing Change in Neurologic Function in Adult Participants With Acute Ischemic Stroke: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Efficacy Study of Intravenous (IV) Elezanumab Assessing Change in Neurologic Function in Adult Participants With Acute Ischemic Stroke (NCT04309474), a randomized phase 2 study. The primary outcome is Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period.

2. Clinical Question

The study’s stated purpose was to assess safety and efficacy and evaluate change in neurological function after acute ischemic stroke. Its primary outcome combines NIHSS observations over the treatment period rather than describing neurological status at a single visit. The registry also lists responder status based on the modified Rankin Scale at Week 52 as a secondary outcome. That outcome is a different way of describing participant status and does not replace the primary NIHSS comparison.

The central statistical question is whether the estimated between-group difference is sufficiently precise to distinguish a group difference from no difference on the outcome scale. The registry’s primary confidence interval includes values on either side of no difference. A clinical threshold for an important difference is not reported in the registry record, so the posted estimate cannot establish whether any particular difference would be clinically meaningful.

3. Trial Design

This was a randomized, parallel-group, placebo-controlled Phase 2 study sponsored by AbbVie. The registry record lists triple masking. Its brief summary describes the study as double-blinded and says participants and study doctors would not know treatment assignment. Which roles are included in the registry’s triple-masking classification is not reported in the registry record.

The record lists enrollment of 121 participants, with a primary completion date of 2024-04-18 and status completed. The study began on 2020-11-09. The brief summary describes a 52-week study and says approximately 120 subjects would be enrolled at 45 sites worldwide. These are descriptions of the planned study; the record separately lists the actual enrollment.

Participants were assigned to receive elezanumab or placebo. The elezanumab arm description specifies 1800 mg, while the placebo arm description identifies placebo for elezanumab. The summary describes intravenous infusion within 24 hours of last known normal and then every 4 weeks for 48 weeks, for a total of 13 doses. It also describes regular hospital or clinic visits during the study.

The primary analysis concerns NIHSS total score area under the curve from Day 1 through Week 52, using the Full Analysis Set. The registry describes a monthly-adjusted area under the curve derived by the trapezoidal method, with contrasts from a Mixed Model with Repeated Measures. The listed visit schedule includes Day 1, Day 2-4, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 52.

The registry identifies a secondary outcome of modified Rankin Scale responder status at Week 52. Details of the responder definition and the full eligibility criteria are not reported in the registry record. The rationale for the planned enrollment, including any sample-size justification, is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set Note: The AUC for each treatment group, as well as the difference in AUCs (placebo minus elezanumab) and their respective standard errors and confidence intervals are presented.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period, measured over Day 1 through Week 52.

The primary endpoint is the NIHSS total score area under the curve during the treatment period, from Day 1 through Week 52. The NIHSS is a neurological examination that measures impairment across domains including consciousness, gaze, visual field, facial palsy, arm and leg motor ability, limb ataxia, sensation, language, dysarthria and extinction or inattention. Its total range is 0 to 42 points, with higher scores indicating impairment.

An area under the curve combines measurements across visits into a summary of the outcome over time. In this study, the registry says the monthly-adjusted area under the curve for each group was derived using the trapezoidal method. The treatment contrast came from a Mixed Model with Repeated Measures. The posted time frame spans Day 1 through Week 52, with visits from Day 1 and Day 2-4 through the later weekly assessments.

This kind of repeated-measure summary is used to represent the course of measured neurological impairment across the treatment period, rather than relying only on one assessment. It can incorporate the sequence of scores at scheduled visits, but the resulting summary depends on how the measurements and model are handled. The registry does not report a threshold for a clinically important difference in area under the curve. The estimate should therefore be read as a statistical comparison on the reported scale, not as a direct judgment about clinical importance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the confidence interval communicate?

A confidence interval describes the uncertainty around an estimated contrast under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval leaves more uncertainty about the plausible values. The primary estimate is 0.71, with a 95% confidence interval from -0.764 to 2.175. Because this interval crosses zero, the posted result is compatible with no group difference as well as with differences in either direction. A confidence interval is not a guarantee that the true value lies within its limits, nor does it show the probability that a treatment effect is real.

The arm-specific least-squares means also have 95% confidence intervals. These intervals describe uncertainty in each modeled group estimate; they should not be substituted for the confidence interval on the direct between-group contrast. The contrast is the relevant estimate for the question of how the groups compare.

Why use area under the curve?

The NIHSS is collected repeatedly during the treatment period. An area-under-the-curve summary combines measurements over time, so the result reflects the pattern of scores across scheduled assessments rather than a score at only one visit. The registry says the area under the curve was monthly-adjusted and calculated using the trapezoidal method. In general, the trapezoidal method approximates the area between successive observations by treating each interval as a straight-line segment. The registry’s use of a monthly adjustment and its detailed formula are not fully described in the posted results; the record refers to a formula in the statistical analysis plan.

Repeated measurements from the same participant are related, so treating each visit as if it were an independent observation would not reflect the structure of the data. A Mixed Model with Repeated Measures is a general approach for modeling repeated outcomes while representing their association over time. The registry states that contrasts from this model were used for the primary analysis. The model’s covariates, covariance structure, estimation details and other specifications are not reported in the registry record.

What does an unadjusted secondary comparison mean?

The secondary modified Rankin Scale outcome is posted as a count of responders in each group, and an unadjusted risk difference is calculated from the posted counts and denominators. A risk difference expresses the difference between the proportions meeting the responder definition in the two groups. Its confidence interval describes uncertainty in that difference. The posted unadjusted p-value is 0.131. An unadjusted analysis does not account for the fact that several outcomes or comparisons may have been examined. The registry lists two outcome measures and two analyses, but a multiplicity plan is not reported in the registry record.

The registry also reports an odds ratio of LS means for the secondary outcome. An odds ratio and a risk difference are different statistical scales: one compares odds, while the other expresses a difference in proportions. They cannot be read as interchangeable estimates. The registry does not give the model details needed to fully assess how its reported odds ratio was estimated.

How should the planning illustrations be read?

The sample-size planning illustrations use the observed secondary effect as their reference and consider planning for 100%, 75% and 50% of that observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms and a normal approximation. They give participants per arm for 80% power and participants per arm for 90% power. These are planning illustrations, not observed power and not evidence about the probability that the trial detected an effect. They do not show that the trial was designed using those assumptions; the trial’s own sample-size justification is not reported in the registry record.

Planning on a fraction of an observed effect can illustrate how the required sample size changes when the target effect is smaller than the observed estimate. Because an observed estimate is uncertain, such illustrations should not be treated as reliable forecasts of future results. A planning calculation also depends on its assumptions, including the target effect and allocation. The posted illustrations do not resolve limitations in the secondary analysis or replace a prospective design justification.

10. Analyses Reported by the Sponsor

The registry’s primary analysis reports the NIHSS area-under-the-curve contrast as 0.71, with a 95% confidence interval from -0.764 to 2.175. The registry does not report a p-value for that primary contrast. The posted group estimates are least-squares means from the described repeated-measures analysis. No separate recalculation of the primary contrast is reported, so there is no alternative primary estimate to compare with the registry analysis.

For the secondary modified Rankin Scale outcome, the registry reports an odds ratio of LS means of 1.74, with a 95% confidence interval from 0.71 to 4.24. The posted unadjusted calculation instead expresses the comparison as a risk difference, with its own confidence interval and unadjusted p-value. Those estimates use different scales and the posted registry analysis is not described in enough detail to establish that they target precisely the same quantity. The difference in presentation is therefore not, by itself, evidence of a contradiction.

The registry marks no discrepancy between the reported analyses and the simple recalculation. The recalculation is an unadjusted comparison from posted summary counts; it does not reproduce a model-based odds ratio of LS means. The registry’s own analysis should be interpreted as the sponsor-reported analysis, while the recalculation serves as a separate, simpler view of the secondary data. Neither resolves the uncertainty in the primary comparison, and a direct numerical comparison between the odds ratio and the risk difference would be inappropriate.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, including the primary NIHSS area-under-the-curve outcome and the secondary modified Rankin Scale responder outcome. It does not report a multiplicity strategy, such as an adjustment to significance thresholds or a prespecified sequence for interpreting outcomes. Without such information, the secondary unadjusted result should be interpreted cautiously: considering multiple outcomes can increase the chance of an apparently notable result arising by chance.

The primary analysis description identifies the Full Analysis Set as its population. The criteria for inclusion in that set, the handling of participants who did not receive assigned treatment, and the handling of protocol deviations are not reported in the registry record. The record includes different denominators for some outcome and safety summaries, but does not explain the reasons for those differences.

Missing-data handling is not reported in the registry record. The primary analysis uses a Mixed Model with Repeated Measures, but the registry does not describe the assumptions about missing observations, any imputation, or sensitivity analyses. A repeated-measures model does not, by itself, demonstrate that missing data have no effect on the estimate; interpretation depends on its assumptions and implementation. Details of the statistical analysis plan referenced in the primary description are not included in the posted results.

The registry record also does not report interim analyses, stopping rules, or a sample-size justification. Their absence from the posted record should not be taken to mean that none were used; the relevant details are not reported in the registry record. These gaps limit the ability to assess whether the analyses followed a prespecified plan, how robust the estimates are to missingness, or how the planned enrollment was linked to a target effect.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: brain oedema (5.0%), ischaemic stroke (5.0%), pulmonary embolism (5.0%), fall (4.9%), covid-19 (3.3%).

The serious adverse event summaries report 23 affected participants among 60 at risk in the placebo group and 18 among 61 at risk in the elezanumab group. Deaths are reported for 7 participants in the placebo group and 1 participant in the elezanumab group. These are descriptive counts; they do not, on their own, establish that treatment caused or prevented an event. The record does not provide a comparative statistical analysis of these safety counts in the posted results.

For other adverse events, the registry reports 52 affected participants among 60 at risk in the placebo group and 49 among 61 at risk in the elezanumab group. Serious and other adverse-event summaries are separate categories in the record. The listed serious terms include BRAIN OEDEMA, ISCHAEMIC STROKE, PULMONARY EMBOLISM, FALL, COVID-19 and PNEUMONIA, with the corresponding percentages reported in the registry. The term list does not establish a causal relationship to study treatment.

Safety counts should be interpreted in light of the recorded denominators and the study’s duration and population. The registry does not provide enough detail in these summaries to assess event timing, exposure-adjusted rates, severity grading, relatedness assessments, or comparative uncertainty. These figures are descriptive registry results, not a complete safety assessment.

13. What the Result Does, and Does Not, Mean

The primary result is an estimate of the difference between groups in NIHSS total score area under the curve from Day 1 through Week 52. Its confidence interval includes zero and extends in both directions. The posted estimate therefore does not establish a clear difference between the groups, and it does not rule out differences in either direction. The absence of a reported primary p-value does not change what the confidence interval shows.

The confidence interval alone cannot determine clinical importance. The registry does not report a threshold for a clinically important difference on this area-under-the-curve scale. Nor does a point estimate that favors one direction prove that the result is reproducible or attributable to treatment. Statistical uncertainty, the analysis population, missing-data assumptions and the clinical meaning of the scale all matter.

The secondary responder result is a separate outcome. It is unadjusted and has its own uncertainty, and the reported odds ratio is distinct from the risk-difference calculation. It should not be treated as confirmation of a primary finding or as a substitute for the primary outcome. The safety counts describe events recorded in each group; they do not establish treatment causation.

These registry results do not establish that elezanumab works or does not work. They describe the estimates and safety counts reported for this completed Phase 2 study. Important interpretation details—including the missing-data approach, full model specification, multiplicity plan, clinical-importance threshold and sample-size justification—are not reported in the registry record. Conclusions beyond the posted estimates would require information that is not included in the record.

14. Why This Trial Matters Statistically

This trial raises several statistical issues common to studies of acute neurological conditions. NIHSS is measured repeatedly, and the primary outcome summarizes the trajectory over the treatment period rather than relying on a single assessment. That approach can make use of the pattern of observations, but the resulting contrast depends on the repeated-measures model and the construction of the area-under-the-curve summary.

The registry’s estimate is accompanied by a confidence interval that crosses zero and is broad enough to include values in either direction. This illustrates why an estimate alone is not an adequate summary of a treatment comparison. Precision and the range of values compatible with the analysis are central to interpretation. The lack of a reported clinical-importance threshold also means the magnitude cannot be translated into a judgment about practical importance from the registry record alone.

The secondary outcome demonstrates another important issue: different summaries can describe the same broad comparison on different scales. A risk difference and an odds ratio are not interchangeable, particularly when details of the model are unavailable. A straightforward recalculation from posted counts can aid transparency, but it does not reproduce a model-based analysis unless the estimand and methods align.

Finally, the record illustrates why prespecified analysis details matter. Multiplicity, missing observations, analysis populations and sample-size rationale all affect how confidently results can be interpreted. These details are not reported in the registry record. Their absence limits statistical assessment, without changing the estimates that are posted.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary outcome is a modeled area-under-the-curve estimate, but the registry does not report the full model specification, including covariates, covariance structure or other estimation details. It refers to a formula in the statistical analysis plan, but that formula is not included in the posted description. The analysis population is named as the Full Analysis Set, while its membership rules are not reported in the registry record.

Missing-data methods and sensitivity analyses are not reported in the registry record. This matters for a repeated-measures outcome observed at several visits: the interpretation of a model-based summary can depend on how incomplete measurements are handled and on assumptions about why they are missing. The different denominators across outcome and safety summaries are not explained in the record.

The registry does not report a multiplicity plan, a sample-size justification, interim analyses or stopping rules. It also does not report a clinical-importance threshold for the primary area-under-the-curve contrast. Those omissions limit assessment of the planned inferential framework and the clinical meaning of the observed estimate.

For the secondary result, the posted risk-difference recalculation is unadjusted, while the registry reports an odds ratio of LS means. The record does not provide enough detail to determine how the model-based result was estimated or fully reconcile the two scales. The responder definition is not reported in the registry record. These are limitations of interpretation, not grounds to replace the registry’s reported analyses with an unsupported conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety and Efficacy Study of Intravenous (IV) Elezanumab Assessing Change in Neurologic Function in Adult Participants With Acute Ischemic Stroke — NCT04309474.
• Registry record last updated 2025-12-22; status last verified 2025-12.
• Results first posted 2025-12-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04309474 is a completed randomized, parallel-group, placebo-controlled Phase 2 study sponsored by AbbVie. It evaluated intravenous elezanumab against placebo in adult participants with acute ischemic stroke. The registry lists enrollment of 121 participants, a study start date of 2020-11-09 and a primary completion date of 2024-04-18.

The primary outcome was NIHSS total score area under the curve during the treatment period, from Day 1 through Week 52. The reported placebo-minus-elezanumab contrast was 0.71, with a 95% confidence interval from -0.764 to 2.175. The interval includes zero and is compatible with differences in either direction. A secondary modified Rankin Scale responder outcome was also posted for Week 52.

The record includes descriptive adverse-event counts and a secondary analysis, but key details about multiplicity, missing-data handling, model specification and sample-size justification are not reported in the registry record. The posted estimates should be interpreted with those limitations in mind.