Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses (NCT02276963), a na phase 1 study. The primary outcome is Change in Neurological Disability - Expanded Disability Scale Score.

2. Clinical Question

This question concerns a treatment combination rather than ublituximab alone. Because glucocorticoids were given alongside ublituximab, the study cannot separate the contribution of either treatment to any observed change. The single-group design also means that changes over time cannot be directly contrasted with outcomes in a concurrent untreated or alternative-treatment group.

The primary outcome is titled as a change in neurological disability and is summarized by median EDSS and inter-quartile range. The registry describes measurements at admission on day 1, discharge 5-21 days later, and 90-day follow-up. It does not report the numerical medians, inter-quartile ranges, or an estimated change between time points. Therefore, the registry record identifies what the study intended to assess, but does not permit a quantitative answer to the clinical question.

3. Trial Design

NCT02276963 is a Phase I, single-center, open-label, single-group study sponsored by Johns Hopkins University. The record lists the study as completed, with a start date of 2016-01 and primary completion in 2017-07. Enrollment is listed as 6. The registered title concerns acute optic neuritis and/or transverse myelitis in NMO and NMOSD, treated with ublituximab plus glucocorticoids.

All participants in the treatment group were assigned to the same regimen: ublituximab 450 mg intravenously once on day 1 and glucocorticoids 1000 mg intravenously daily on days 1-5. The study has no separate comparison arm, and masking is listed as none. Consequently, the design does not support a randomized, like-for-like comparison between the combination and another treatment or control condition. Changes in EDSS are described over time within the treated group.

The distinction between enrollment and outcome availability matters. Although enrollment is 6, the registry says 5 subjects had EDSS measurements at baseline, admission and discharge; 3 subjects had an additional measurement at 90-day follow-up. The reason that outcome measurements are not described for all enrolled subjects is not reported in the registry record.

The record lists one primary outcome measure, change in neurological disability using EDSS. Its timeframe includes admission on day 1, discharge 5-21 days later, and follow-up at 90 days. The measure is summarized as a median with an inter-quartile range. Numerical outcome values and inferential analyses are not reported in the registry record. Details of the protocol’s statistical plan, sample-size justification, and any interim analyses are also not reported in the registry record.

As a Phase I study with a single group and a small number of participants, the design describes an early clinical investigation rather than a controlled estimate of comparative treatment effects. Open-label assessment may also be relevant when interpreting a functional disability scale, because the record does not describe masking of participants or assessors. These design features limit the conclusions that can be drawn from any within-group change, even if numerical outcome results were available.

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.

Before assignment: There were no pre-assignment events.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 5 subjects had EDSS measurements at the first three time points: baseline, admission and discharge. 3 subjects had EDSS scores with an additional EDSS measurement at 90-day follow up.

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.

Population: 1 patient withdrew from the study prior to exposure to drug. 5 subjects were exposed to the drug. 3 patients completed the study with monthly blood tests and 90 day follow up.

6. Primary Endpoint

The registry lists the primary outcome as Change in Neurological Disability - Expanded Disability Scale Score, measured over On admission to the hospital on day 1, on discharge 5-21 days later and on follow up at 90 days.

The primary endpoint is change in neurological disability measured with the Kurtzke Expanded Disability Status Scale (EDSS). The registry describes EDSS as an instrument developed to quantify disability in demyelinating disease and to provide an objective, reproducible measure of functioning. Its score ranges from 0, described as normal, to 10, described as deceased; higher scores represent greater disability.

Repeated EDSS assessments can describe a participant’s disability at different stages of an episode and over follow-up. The registered timeframe is admission on day 1, discharge 5-21 days later, and 90-day follow-up. The registry specifies a median and inter-quartile range, which describe the central value and spread of the observed scores without requiring the scores to follow a normal distribution.

The registry’s outcome title refers to change, but the posted information does not include numerical EDSS scores, medians, inter-quartile ranges, or a numerical change estimate. It also does not specify a threshold for what would count as a clinically important change. Thus, the endpoint definition explains what was measured and when, but the registry record does not provide results with which to characterize the size, direction, or precision of change.

In general, a disability scale can capture a broad functional status rather than a single symptom. That can make it useful for tracking overall neurological disability, while also meaning that the score alone does not explain which symptoms or functions account for a change. The EDSS description and the study’s numerical findings must therefore be distinguished: the former is present, while numerical findings are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study uses a single-group design. In general, this means that outcomes are observed in participants receiving the study regimen without a separate concurrent control group. Measurements at different times can describe how the group’s outcomes vary during follow-up, but they do not provide the direct treatment-versus-control contrast available in a comparative design. Here, the registry lists one treatment group and no masking.

What does the median and inter-quartile range describe?

The primary outcome is summarized using a median and inter-quartile range. In general, the median is the middle value after observations are ordered. The inter-quartile range describes the spread of the central half of those observations. These summaries can be useful when data are skewed or when extreme values could pull the mean away from the typical observation. They describe the observed distribution; on their own, they do not quantify a treatment effect or establish a cause for change.

The registry specifies EDSS assessments at admission, discharge and follow-up, with the discharge assessment 5-21 days after admission and follow-up at 90 days. Its description notes 5 subjects with EDSS measurements at baseline, admission and discharge, and 3 with an additional 90-day measurement. The numerical summaries for those assessments are not reported in the registry record. Thus, the stated summary method can be explained, but it cannot be applied to characterize the observed outcome from the posted results.

What does a repeated assessment contribute?

In general, repeated measurements can show whether scores differ across time points for the participants assessed. They also make the number of observations at each time point important: summaries based on different participant sets may not reflect the same group. When some follow-up measurements are absent, the interpretation depends on why they are absent and how the analysis handles them. Neither the reasons for missing EDSS assessments nor a missing-data method is reported in the registry record.

A within-group comparison is not equivalent to a controlled comparison. General changes over time may reflect multiple influences, including the course of the underlying episode and the co-administered glucocorticoids. Without a comparator, the data cannot isolate the association with the combined regimen from those other influences. Without separate treatment groups, the contribution of ublituximab alone cannot be estimated.

What is and is not reported about inference?

In general, inferential analyses use sample data to estimate uncertainty or test a specified hypothesis. A confidence interval communicates a range of values compatible with an estimate under the analysis assumptions. A p-value addresses how unusual the data would be under a specified null hypothesis and model; it is not a measure of clinical importance. The registry record does not report a confidence interval, p-value, hypothesis test, or numerical estimate for the primary EDSS outcome. It lists no analyses. The statistical analysis plan, including any model or adjustment strategy, is not reported in the registry record.

The record lists one primary outcome measure, but that alone does not establish the full set of analyses conducted or planned. Whether additional outcomes or comparisons were examined, and whether any adjustment for multiple testing was planned or used, is not reported in the registry record. Without that information and the numerical findings, a reader cannot assess the role of selective reporting or the robustness of any inferential conclusion.

How should the planning illustration be read?

In general, a sample-size planning calculation asks how many participants a future study might need under stated assumptions. It is not a measure of the power actually achieved by a completed study. The planning illustration associated with this analysis is described as using the observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. It is a planning exercise, not evidence that the trial had a particular probability of detecting an effect.

Those assumptions do not describe this trial’s design: the registry lists a single group, not equal allocation between two arms. The illustration should therefore be interpreted as a hypothetical design calculation rather than as a description of the enrolled study. Sample sizes from a planning exercise do not replace the trial’s observed results, and they should not be called observed power. The numerical planning outputs and the underlying observed effect are not reported in the registry record.

More generally, sample-size calculations depend on assumptions about the effect of interest, variability, analysis, and error rates. If those assumptions differ from what is observed in a future study, the planned sample size may not deliver the intended precision. The registry record does not report the trial’s own sample-size justification. That absence prevents reconstruction of the original design rationale; it does not establish what rationale investigators used.

Finally, the safety counts are descriptive rather than a substitute for comparative inference. General statistical reasoning cautions that a small group offers limited information about the frequency of rare events. The record reports counts but does not provide comparative safety estimates, event terms for other adverse events, or uncertainty intervals. These limitations should be kept separate from the EDSS endpoint, for which numerical results are also not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure: change in neurological disability measured by EDSS. It does not report numerical values for that outcome or list any analyses. The registry record does not describe a statistical analysis plan, specify how a primary comparison was defined, or report whether multiple time points were analyzed separately or jointly.

In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. Repeated testing can increase the chance of a nominally unusual result, so a prespecified analysis plan and any adjustment strategy help readers interpret inferential findings. Although one primary outcome is listed, whether investigators examined additional outcomes or analyses and whether any multiplicity procedure was planned or used are not reported in the registry record.

The outcome population is not identical at each follow-up stage. The record states that 5 subjects had EDSS measurements at baseline, admission and discharge, and 3 had an additional EDSS measurement at 90-day follow-up. Reasons for unavailable measurements, the handling of missing data, and whether any imputation or sensitivity analysis was conducted are not reported in the registry record.

The record also does not define analysis populations, such as which enrolled participants were included in each outcome analysis or how protocol deviations were handled. This matters because enrollment is listed as 6, while the EDSS description identifies 5 and 3 participants with measurements at specified stages. No conclusions about the impact of missingness or the composition of an analysis set can be drawn without further detail.

11. 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 non-serious adverse event terms

The safety record lists 0 serious adverse events among 5 participants at risk in the ublituximab plus glucocorticoids group. It lists 3 participants with other adverse events among 5 at risk and 0 deaths. These are counts for the treated group, not comparisons with a control group.

The record lists no serious adverse-event terms. It does not identify the types of other adverse events, so their clinical nature and severity cannot be described from the posted information. The safety information also does not establish whether events were judged related to either study treatment. The event observation period and detailed collection procedures are not reported in the registry record.

These counts should be read descriptively. In general, observing no serious adverse events in a small group does not show that the risk is absent; uncommon events may not appear in a study of limited size. Conversely, the record’s count of other adverse events does not by itself establish that treatment caused them. Without event descriptions, timing, attribution, and a comparator, the safety profile cannot be characterized in detail.

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

The registry record establishes that a Phase I, single-center, open-label study evaluated ublituximab given with glucocorticoids in a single group of people with NMO or NMOSD and acute optic neuritis and/or transverse myelitis. It specifies an EDSS outcome and measurement times, and it reports limited adverse-event counts. It does not provide numerical EDSS results, so the size or direction of disability change cannot be described from the posted results.

The record does not show whether the regimen caused a change in disability. A single-group study cannot separate changes following treatment from changes that might occur over time for other reasons. The concurrent use of glucocorticoids also means that an outcome cannot be attributed to ublituximab alone. No randomized comparison or like-for-like control group is listed.

The listed safety counts describe what was recorded among the participants at risk: 0 serious adverse events, 3 participants with other adverse events, and 0 deaths. The types of other adverse events are not reported in the registry record, and the listed counts do not by themselves establish causation or comparative risk.

In general, a study’s result should be interpreted in light of its endpoint, analysis, precision and design. Here, the EDSS summary values and uncertainty estimates are absent, and the analysis plan is not reported. The outcome population also declines from 5 subjects with measurements at the first three time points to 3 with a 90-day assessment. The implications of those missing measurements are unknown.

Accordingly, the record supports a description of the study question, regimen, outcome schedule and reported safety counts. It does not support a quantitative conclusion about EDSS change, a comparison with another treatment, or a causal conclusion about either treatment component. These are limits of what the registry record reports, rather than evidence for a particular unreported outcome.

13. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly defined clinical outcome and the absence of its numerical results in the registry record. EDSS is described, its direction is explained, and assessment times are specified. But without medians, inter-quartile ranges, or estimates of change, readers cannot assess the observed disability profile or its precision. A precise endpoint definition is not a substitute for a reported result.

The design also illustrates why a within-group change and a comparative treatment effect are different quantities. Repeated scores can describe how participants’ disability varies during the study. Without a concurrent control group, however, those observations cannot show how outcomes would have differed under another treatment or no study regimen. The combination of ublituximab and glucocorticoids further prevents attribution of any change to one component.

The difference in outcome availability across time points is another important statistical feature. The record describes EDSS data for 5 subjects at baseline, admission and discharge, and for 3 at 90-day follow-up. Reporting the number assessed at each stage helps readers see the scope of the available data, but reasons for missing measurements and methods for handling them remain unknown.

The safety figures also require restrained interpretation. Counts of serious and other adverse events are informative as descriptive observations, but a small single group and absent event details do not establish comparative safety or rule out uncommon harms. The registry reports no serious events and no deaths, while 3 participants had other adverse events; event types and attribution are not given.

These features make the record useful for understanding what was studied and what information is available, while also showing why design, missingness and result reporting matter. A study’s endpoint and treatment rationale cannot replace its observed outcome estimates or an appropriate comparison.

14. 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 main trial-specific limitation is the absence of numerical primary outcome results. Although the registry defines EDSS, its summary statistic and assessment schedule, it does not report the EDSS values or changes. This prevents evaluation of the endpoint’s direction, magnitude and precision.

The design has one treatment group, is open label and has no masking. There is no concurrent comparison group to distinguish treatment-associated change from other changes over time. Since ublituximab was given with glucocorticoids, the effect of either component cannot be separated. The record does not report a protocol or statistical analysis plan that would clarify the intended analysis.

Enrollment is listed as 6, but the outcome description identifies 5 subjects with EDSS measurements at baseline, admission and discharge, and 3 with an additional 90-day measurement. The reason for the difference and the approach to missing observations are not reported in the registry record. Follow-up summaries may therefore represent a smaller subset, and the degree of any resulting bias cannot be assessed.

The safety information is also limited: no serious-event terms are listed, other adverse-event types are not reported, and the record does not describe event attribution or observation procedures. With no comparison group, the counts cannot establish relative risk. The trial’s sample-size justification, interim analyses, and detailed analysis populations are not reported in the registry record. These gaps constrain interpretation independently of the clinical rationale for studying the regimen.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses — NCT02276963.
• Registry record last updated 2019-06-06; status last verified 2019-06.
• Results first posted 2019-06-06.
• 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.

18. Record Summary

NCT02276963 is a completed Phase I, single-center, open-label, single-group study sponsored by Johns Hopkins University. The registry lists enrollment of 6 and a start date of 2016-01, with primary completion in 2017-07. The intervention was ublituximab 450 mg intravenously once on day 1 plus glucocorticoids 1000 mg intravenously daily on days 1-5.

The primary outcome was change in neurological disability measured by EDSS. The registered timeframe included admission on day 1, discharge 5-21 days later, and 90-day follow-up. Numerical EDSS results are not reported in the registry record. The record states that 5 subjects had measurements at baseline, admission and discharge, and 3 had an additional 90-day measurement.

Safety counts list 0 serious adverse events among 5 at risk, 3 participants with other adverse events among 5 at risk, and 0 deaths. Other-event types are not reported. The record does not list a control group or report inferential analyses.