A Study to Evaluate the Long-Term Safety of MEDI-545 in Adult Participants With Systemic Lupus Erythematosus or Myositis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Long-Term Safety of MEDI-545 in Adult Participants With Systemic Lupus Erythematosus or Myositis (NCT00979654), a na phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

The study’s stated objective was to assess the safety and tolerability of sifalimumab in adults with active systemic lupus erythematosus or active dermatomyositis or polymyositis who had taken part in the named earlier studies. It was not structured as a randomized comparison between sifalimumab and another treatment or a control. Its primary outcome therefore describes events among participants treated in this study, rather than a contrast in event rates between assigned groups.

The record lists systemic lupus erythematosus as a condition and identifies the eligible disease groups in the study summary. It does not report separate primary safety results for each diagnosis. The clinical question addressed by the posted outcome is consequently a pooled safety question across the study population, not a diagnosis-specific comparison. The registry record does not report a treatment-effect question for disease activity or clinical benefit as the primary objective.

3. Trial Design

This was a Phase 2, open-label, single-group study of sifalimumab. The record gives allocation as not applicable and masking as none. Accordingly, participants were not assigned through a reported randomized comparison, and the design does not include a concurrent control arm. The study is marked completed. Enrollment was 118, while the safety population description specifies participants who received at least one dose; the posted safety outcome lists 103 participants at risk. The registry record does not report further participant-flow details that explain the difference between total enrollment and the number at risk.

The intervention was intravenous sifalimumab. The arm description states a fixed dose of 500 mg every 2 weeks on Day 1, Week 2, and Week 4, followed by dosing every 4 weeks for a total of 156 weeks. It also notes that the initial fixed dose of 500 mg was increased to 600 mg with a subsequent protocol amendment. The registry record does not report how many participants received each dose or when individual participants changed dose.

The study started in 2010-08 and had a primary completion date of 2015-03. These registry dates describe the study record and do not give individual exposure or follow-up times. The primary safety timeframe is stated as from the start of study-drug administration until week 182. Treatment-emergent events were defined as events arising between administration of investigational product and 30 days after the last dose, if absent before treatment or worsened relative to the pretreatment state.

Because this is a single-group safety study, its results can describe the events recorded among participants who received sifalimumab in the study. They cannot, by design alone, isolate how those events compare with what would have occurred under another treatment or without study treatment.

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: A total of 118 participants were Screened out of which 15 participants did not meet eligibility criteria and were considered screen failures, and 103 participants were entered into the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population included all participants who received at least one dose of investigational product.

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 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), measured over From start of study drug administration until week 182.

The primary outcome is the number of participants with treatment-emergent adverse events and the number with treatment-emergent serious adverse events. It measures participants affected, not the total number of event episodes. The registry defines an adverse event as an untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event is an adverse event resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, a congenital anomaly, or another outcome considered significant.

For an event to be treatment-emergent under the registry definition, it had to occur after investigational product administration and through 30 days after the last dose, and either be absent before treatment or worsen relative to the pretreatment state. The primary timeframe extends from the start of study-drug administration until week 182. These definitions set the period and event criteria used for the safety count; they do not establish that treatment caused an event merely because it was recorded during the treatment-emergent period.

Counting participants with events is useful in a safety-focused study because it indicates how many people in the observed safety population were affected. The serious-event count separately identifies events meeting the registry’s seriousness criteria. In a single-group, open-label study, these counts describe observed safety experience, but do not estimate a controlled difference in risk or establish causation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with treatment-emergent events. This is a binary participant-level outcome: for each participant, the relevant distinction is whether an event meeting the outcome definition was recorded. The reported counts retain the number affected and the number at risk. They do not indicate how many times an affected participant experienced an event, how long each event lasted, or whether multiple event terms occurred in the same participant.

What does a count describe?

A count is a direct summary of observed cases in the population being assessed. Its interpretation depends on the population definition, the event definition, and the observation window. The safety population is defined as all participants who received at least one dose of investigational product. The primary timeframe runs from the start of study-drug administration until week 182, while treatment-emergent events are defined relative to dosing and the 30 days after the last dose. Those details matter because a participant cannot contribute to an event count in the same way if eligibility or observation differs.

In general, counts are straightforward to understand but are not, by themselves, standardized for different amounts of follow-up. A count also does not reveal the distribution of events by severity, duration, or recurrence unless those features are separately reported. The serious-event classification provides an additional definition based on specified outcomes or clinical significance, rather than simply the number of events.

Why is the design important?

This study is open-label and single-group, with no randomized allocation or concurrent comparator reported. Thus the primary safety summaries are descriptive. A comparison intended to estimate a treatment effect generally needs a suitable comparator and a clearly defined contrast; neither is part of the posted design. Differences between participants, changes in care over time, underlying illness, and other circumstances may all be relevant to observed events, but the record does not quantify their contributions.

Randomization, when used, helps balance measured and unmeasured participant characteristics between comparison groups on average. It is not reported for this study. Open-label status means masking is not reported, so knowledge of treatment could potentially affect reporting or assessment; the registry record does not state whether or how this was evaluated. These general design considerations are not evidence that any particular bias occurred in this study.

What would an uncertainty interval add?

In general, a confidence interval expresses sampling uncertainty around an estimate under a specified statistical model. A narrow interval indicates greater precision under that model, while a wide interval indicates less precision. A confidence interval does not correct for study-design limitations, missing information, or systematic bias. The registry record does not report confidence intervals for the primary safety counts, so the precision of an estimated event frequency cannot be evaluated from an interval in the posted results. No unreported interval should be reconstructed from the counts.

Over-dispersion is a general concern when outcome variability is greater than a chosen statistical model expects. It can make standard errors too small if a model assumes less variability than the data exhibit. The primary safety result is reported as a participant count, and the registry record does not describe a model for these counts or report an over-dispersion assessment. It would therefore be inappropriate to claim that over-dispersion was tested or corrected.

How should planning illustrations be read?

The planning assumptions associated with any sample-size illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. They are planning illustrations, not observed power and not a description of this single-group study’s actual allocation. The assumptions also do not establish that the registry used those methods to plan enrollment; the sample-size justification is not reported in the registry record.

More generally, a sample-size calculation describes how many participants a hypothetical design might require to detect a stated effect under chosen assumptions. Its output depends on the effect size, variability or event frequency, significance level, desired power, allocation, and analysis method. A planning calculation cannot show that the study had a particular probability of finding a result after it was completed. In this record, the planning assumptions describe a two-arm setup, whereas the observed study is single-group, so the illustrations should not be interpreted as a direct assessment of this trial’s design adequacy.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary safety outcome and secondary pharmacokinetic and anti-drug antibody measures. It reports 0 analyses. The registry record does not describe a multiplicity adjustment, an ordering of confirmatory tests, or another strategy for controlling the chance of false-positive findings when several outcomes are assessed. Without such information, it is not possible to determine how multiple outcomes were handled in the study’s analysis.

The record does not report a statistical analysis plan for the primary endpoint, including any planned method for summarizing or comparing event counts. It also does not report interim analyses or stopping rules. Their absence from the record should be read as missing documentation, not as proof that a particular procedure was or was not used outside the registry entry.

The safety population is defined as participants receiving at least one dose of investigational product. The posted result gives 103 participants at risk, while total enrollment is 118. Participant-level reasons for not appearing in the safety population, if any, are not reported in the registry record. Missing outcome data, loss to follow-up, censoring, and methods for handling incomplete safety information are also not reported in the registry record. No imputation or other missing-data method should be assumed.

These gaps limit assessment of how complete the event ascertainment was and how the reported population relates to all enrolled participants. They also prevent evaluation of whether results were analyzed exactly as planned. The available counts remain interpretable as posted descriptive safety summaries, but the record does not support claims about prespecified testing, adjustment for multiple outcomes, or robustness to missing data.

11. Safety Results

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

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: cellulitis (2.9%), musculoskeletal chest pain (2.9%), atrial fibrillation (1.9%), diverticulitis (1.9%), urinary tract infection (1.9%).

The safety results list 27 participants with serious adverse events among 103 at risk. The other-adverse-event category lists 89 participants among 103 at risk. These are participant counts, not totals of event episodes, and the categories should not be added to create a total because the record does not specify whether participants could be counted in both. The denominator is the reported population at risk for the adverse-event group.

The most frequent serious-event terms listed are cellulitis and musculoskeletal chest pain, each at 2.9%. Atrial fibrillation, diverticulitis, and urinary tract infection are each listed at 1.9%; cardiac tamponade is listed at 1.0%. The registry record does not provide counts alongside these term percentages in the registry record for this interpretation, so they are best read as the posted percentages rather than converted into participant counts. Deaths are not reported in the registry record.

Seriousness is defined by outcomes such as death, hospitalization, life-threatening experience, significant disability or incapacity, congenital anomaly, or another reason for clinical significance. Seriousness is not the same as causality. These results describe events recorded under the registry’s definitions during the specified safety observation period; without a comparator, they do not quantify excess risk attributable to treatment.

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

The results show that treatment-emergent adverse events were recorded among participants in the sifalimumab safety population, including serious events. Specifically, the record lists 27 participants with serious adverse events and 89 in the other-adverse-event category, each among 103 at risk. These observations describe the experience reported for this study population and its stated observation framework.

They do not establish that sifalimumab caused each event. The treatment-emergent definition identifies events by timing and change from the pretreatment state, while the serious-event definition classifies seriousness by outcomes or clinical significance. Neither definition alone establishes causation. Since the trial has no randomized comparator, it also cannot show how the counts compare with an alternative treatment or with no study treatment.

The results do not establish benefit for systemic lupus erythematosus, dermatomyositis, or polymyositis. The primary outcome is safety-focused, and the available results do not include a disease-activity estimate or a treatment-effect comparison. Secondary outcomes listed in the record concern pharmacokinetic measures and anti-drug antibody status; results for those outcomes are not reported in the registry record in the registry record for this interpretation.

Nor do the counts alone describe the timing, duration, recurrence, or clinical course of events. The registry record does not report confidence intervals for the primary outcome, a statistical model, or additional detail needed to assess precision. The most defensible reading is therefore descriptive: these are the reported numbers of participants affected in the safety population, not a causal estimate, a comparative risk estimate, or a guarantee about an individual participant’s experience.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical statistics: a safety count can be useful without answering a comparative treatment question. The registry reports participants affected by treatment-emergent adverse events and serious adverse events, and those summaries help describe what was recorded during the study. Their meaning depends on the safety population, event definitions, and exposure period, all of which need to be considered alongside the numbers.

The design also demonstrates why the existence of a reported outcome is not the same as evidence from a controlled contrast. This was an open-label, single-group Phase 2 study, with allocation listed as not applicable. Its safety results can characterize the observed participants, but there is no randomized comparison in the record from which to estimate a difference between treatment groups. Recognizing that distinction prevents descriptive data from being read as proof of comparative safety or causation.

The record also highlights the importance of reporting analytic details. It lists multiple outcomes but does not report analyses, confidence intervals, missing-data procedures, or a multiplicity strategy. Those details affect how fully readers can judge precision, completeness, and the interpretation of multiple outcomes. Their absence does not erase the reported counts, but it does constrain the conclusions that can be drawn from them.

Finally, planning illustrations should be kept separate from what the trial actually observed. Hypothetical sample-size assumptions do not constitute observed power, and assumptions based on a two-arm comparison do not change the single-group design. Keeping design, outcome definitions, analytic uncertainty, and planning calculations conceptually separate is central to a careful statistical reading of clinical safety records.

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 primary limitation for interpreting the results is the absence of a concurrent comparator. Without randomization or a control group, the reported counts cannot distinguish treatment-related events from events associated with underlying illness, background risk, or other circumstances. The open-label design also means that masking is not reported; the registry record does not describe how awareness of treatment was addressed in event assessment or reporting.

The study population includes adults with systemic lupus erythematosus or myositis, with the latter described as dermatomyositis or polymyositis in the objective. The record does not report separate primary safety results by diagnosis, dose, or earlier-study participation. It also does not report how many participants received 500 mg or 600 mg after the protocol amendment, so the pooled counts cannot be interpreted as dose-specific safety summaries.

Total enrollment was 118, whereas the posted safety group lists 103 at risk. Although the safety population is defined by receipt of at least one dose, participant flow and reasons for the enrollment-to-safety-population difference are not reported in the registry record. Completeness of follow-up and handling of missing event information are likewise not reported. The available primary results do not include confidence intervals, adjusted analyses, or event-level detail on timing and recurrence.

The registry reports the study as completed and gives its primary completion date as 2015-03, but those milestones do not establish each participant’s duration of treatment or follow-up. The primary timeframe is stated through week 182, and the dosing description states a total planned duration of 156 weeks. Actual exposure by participant is not reported in the registry record. These limitations support a descriptive reading of the posted counts and caution against extending them to comparative, dose-specific, or causal conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Long-Term Safety of MEDI-545 in Adult Participants With Systemic Lupus Erythematosus or Myositis — NCT00979654.
• Registry record last updated 2016-10-27; status last verified 2016-08.
• Results first posted 2016-08-23.
• 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

NCT00979654 is a completed Phase 2, open-label, single-group study of intravenous sifalimumab, also identified as MEDI-545, in adults with systemic lupus erythematosus or myositis. The study began in 2010-08, with primary completion in 2015-03, and total enrollment of 118. The regimen description specifies an initial 500 mg dose, later increased to 600 mg by protocol amendment.

The primary outcome counts participants with treatment-emergent adverse events and treatment-emergent serious adverse events from the start of study-drug administration through week 182. The safety population includes participants who received at least one dose. Posted results list 27 participants with serious adverse events and 89 in the other-adverse-event category, among 103 at risk. The registry lists 9 outcome measures and 0 analyses. It does not report a randomized comparator, confidence intervals, multiplicity methods, or missing-data procedures in the record described.