Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis (NCT02531633), a randomized phase 3 study. The primary outcome is Part A: Number of Participants in Sustained Remission at Week 52.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study of sirukumab for giant cell arteritis. The registry record identifies placebo as the control and lists GlaxoSmithKline as the sponsor. The study started on 2015-10-16, had a primary completion date of 2018-03-21, and is recorded as terminated. The reason for termination is not reported in the registry record.

The planned study had two parts. Part A was a 52-week double-blind treatment phase, in which sirukumab or matching placebo was paired with a prednisone taper. Three sirukumab regimens were described: 100 mg subcutaneously every 2 weeks with either a 6-month or 3-month taper, and 50 mg every 4 weeks with a 6-month taper. Placebo groups used either a 6-month or 12-month taper. The registry summary described approximately 204 participants as the planned Part A enrollment; the record reports actual enrollment of 161.

Part B was planned as a 104-week extension for participants completing Part A, with open-label sirukumab available depending on disease status. A 16-week follow-up phase was described if applicable. The record also lists Part B outcomes, but the primary outcome discussed in the posted results is from Part A. It does not describe how the termination affected completion of each planned phase or the availability of follow-up for individual participants.

The posted primary outcome gives group counts of 3 of 17, 2 of 13, 1 of 9, 0 of 9, and 0 of 7, respectively, across the three sirukumab groups and two placebo groups. Its analysis description states that participants who completed the Week 52 visit or withdrew before 10 Oct 2017 were included. This qualification matters when interpreting the listed denominators alongside the outcome’s Intent-to-Treat population definition.

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: This study was conducted in 2 distinct parts (Part A and Part B), Part A was a 52-week double-blind treatment phase and Part B was a 104-week long-term extension phase with the option to receive open-label sirukumab (SIR) (up to a 52-week duration of open-label treatment). This study was terminated early by sponsor.

Only the first 6 of 10 groups are shown.

Part A (52 Weeks)

Reasons for not completing this period:

Part B (104 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population comprised of all randomized participants who received at least 1 dose of SC investigational product (IP).

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 Part A: Number of Participants in Sustained Remission at Week 52, measured over Week 52.

The primary endpoint was the number of participants in sustained remission at Week 52. It is a binary participant-level outcome: each included participant either met the stated definition or did not. Sustained remission required four conditions: remission at Week 12, no disease flare between Week 12 and Week 52, completion of the assigned prednisone taper, and no requirement for rescue therapy through Week 52.

Remission was defined as the absence of clinical signs and symptoms of giant cell arteritis together with normalization of erythrocyte sedimentation rate and C-reactive protein. The registry definitions give the laboratory thresholds as ESR <30 millimeters per hour and CRP <1 milligram/deciliter. A flare was defined as recurrence of symptoms attributable to active giant cell arteritis, with or without elevations in ESR or CRP.

Combining clinical status, laboratory measures, taper completion, and rescue-treatment use makes the endpoint a measure of sustained disease control under the assigned regimen, rather than a single measurement at Week 52. It also means the endpoint can be missed when any one of its required elements is not met. The registry record does not report further details about adjudication or how unavailable component measurements were handled.

The posted counts are 3, 2, 1, 0, and 0 for the five groups, with listed denominators of 17, 13, 9, 9, and 7. These are descriptive counts, not by themselves estimates of a treatment effect. No confidence intervals or inferential comparison results are reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the event occurred. In this study, the event was meeting all criteria for sustained remission at Week 52. The primary outcome is therefore presented as the number of participants meeting the criteria in each group, alongside the corresponding denominator. A count retains the observed number of events, while the denominator indicates how many participants contributed to that group’s posted result.

What can be learned from counts alone?

Counts can describe what was observed in each arm, but a comparison requires an estimate of the contrast between arms and its uncertainty. A confidence interval is a range of values compatible with the data under the statistical model and assumptions used. It conveys how imprecise an estimate may be; it is not a guarantee that the true value lies within the interval. The registry record does not report confidence intervals for this endpoint, and it states that two-arm comparison values were missing or not estimable. No p-values or inferential results are posted.

In general, small event counts can yield imprecise estimates, and a zero count in a group does not by itself show that the underlying event probability is zero. The five observed group counts are 3, 2, 1, 0, and 0, with denominators of 17, 13, 9, 9, and 7. These uneven denominators and sparse events make it especially important not to treat the raw pattern as a conclusive ranking of regimens. A comparison needs an appropriate statistical method and an uncertainty estimate, neither of which is available in the posted primary analysis.

Why does the endpoint definition matter?

The endpoint combines multiple requirements: remission at Week 12, absence of flare through Week 52, taper completion, and no rescue therapy. This makes the result clinically and statistically different from a single-visit remission measure. A participant who fails any required condition does not meet the composite definition, even if other parts are satisfied. The registry description defines remission using symptoms and laboratory values, with ESR <30 millimeters per hour and CRP <1 milligram/deciliter, and defines flare by recurrence of symptoms attributable to active disease, with or without laboratory elevations.

Composite outcomes can be useful when the research question concerns an overall state assembled from several relevant conditions. Their interpretation depends on all components and on how each is measured. The registry record does not report component-level counts for the primary outcome, adjudication procedures, or methods for resolving disagreements about the endpoint.

How should the sample-size illustrations be read?

The stated planning approach assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It defines the effect to detect as a stated fraction of the observed effect. These are planning assumptions for illustrations, not a report of the trial’s prospective design calculations. The record does not report the original sample-size justification, and the illustrations must not be interpreted as observed power. Power is a design concept based on assumptions about a target effect and analysis; it cannot establish whether a result is credible after the data are observed.

When the event count is sparse, planning calculations can be sensitive to the assumed effect and method. General statistical practice would also consider whether a normal approximation is appropriate for the event pattern and group sizes. The registry record does not state how the illustration method was validated for this outcome, nor does it provide a trial-specific planned effect or variance assumption. No additional numerical planning results are described in the record.

What is the role of the analysis population?

The endpoint text calls the population Intent-to-Treat and defines it as randomized participants receiving at least 1 dose of subcutaneous investigational product. It also restricts inclusion to those completing the Week 52 visit or withdrawing before 10 Oct 2017. Analysis-population definitions affect which participants contribute to the estimate and how missing outcome information is treated. Here, the registry record does not report a fuller account of exclusions, missing values, or sensitivity analyses, so the implications of that inclusion rule cannot be resolved from the posted information.

The record lists 92 outcome measures and 91 posted secondary outcomes, but those counts do not tell readers which analyses were prespecified, which were conducted, or how the primary endpoint was prioritized among possible analyses. The record reports zero analyses for the posted binary endpoint. Statistical interpretation should therefore remain limited to the descriptive results and methods actually documented.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("PartA:SIR 100 mg SC q2w+6 Month Prednisone", "PartA:SIR 100 mg SC q2w+3 Month Prednisone", "PartA:SIR 50 mg SC q4w+6 Month Prednisone", "PartA:Placebo SC q2w + 6 Month Prednisone", "PartA:Placebo SC q2w + 12 Month Prednisone")
n      <- c(17, 13, 9, 9, 7)
events <- c(3, 2, 1, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  PartA:SIR 100 mg SC q2w+6 Month Prednisone  17  3  17.6  3.8  43.4  6.2  41.0  6.4  41.4
ARM  PartA:SIR 100 mg SC q2w+3 Month Prednisone  13  2  15.4  1.9  45.4  4.3  42.2  4.7  42.8
ARM  PartA:SIR 50 mg SC q4w+6 Month Prednisone  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  PartA:Placebo SC q2w + 6 Month Prednisone  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  PartA:Placebo SC q2w + 12 Month Prednisone  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists many outcome measures, including 91 posted secondary outcomes, as well as the primary Week 52 sustained-remission endpoint. It does not report a multiplicity strategy for controlling the chance of false-positive findings across multiple outcomes or comparisons. It also does not report a hierarchy of tests, a prespecified testing sequence, or whether any secondary outcomes were intended to be confirmatory. Without those details and posted inferential analyses, the secondary outcome list should not be read as a set of independently established effects.

The primary endpoint analysis description includes participants who completed the Week 52 visit or withdrew before 10 Oct 2017. Although the population is defined as randomized participants who received at least 1 dose, the record does not fully explain how participants not meeting that analysis inclusion rule were handled. Methods for imputation, censoring, missing-data assumptions, or sensitivity analyses are not reported in the registry record. It is therefore not possible to determine from the posted information how robust the outcome counts are to missing Week 52 data.

The registry record does not report an analysis plan, interim analyses, stopping boundaries, or a trial-specific sample-size justification. Its status is terminated, but the reason and any impact on planned analyses are not reported. The outcome description and available counts do not establish whether the analysis followed a prespecified plan. These gaps limit assessment of multiplicity, selection of reported analyses, and the handling of incomplete data.

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: syncope (7.7%), clostridium difficile colitis (3.8%), pneumonia (3.8%), rib fracture (3.8%), spinal osteoarthritis (3.8%).

The registry lists serious adverse events and other adverse events in separate group summaries, with the number at risk and the number affected. For Part A, serious adverse events affected 8 of 42 participants in the sirukumab 100 mg every 2 weeks plus 6-month prednisone group, 6 of 39 with the same sirukumab schedule plus 3-month prednisone, 6 of 26 in the sirukumab 50 mg every 4 weeks plus 6-month prednisone group, 5 of 27 with placebo plus 6-month prednisone, and 6 of 27 with placebo plus 12-month prednisone. The registry reports zero deaths in each listed group.

These group figures are descriptive. They do not adjust for exposure duration, differences in follow-up, or the distinct prednisone taper regimens. The Part B groups have small numbers at risk, and their entries should not be compared directly with the larger Part A groups. The record does not report a statistical safety comparison or enough detail to establish causal attribution for an event.

The most frequently listed serious-event term is syncope at 7.7%; Clostridium difficile colitis, pneumonia, rib fracture, spinal osteoarthritis, and hypersensitivity vasculitis are each listed at 3.8%. These percentages should be understood as registry-reported event-term figures, not as estimates of comparative risk between treatment groups. The record does not give further context for those terms in the summary.

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

The posted primary data show that the registry recorded some participants meeting its sustained-remission definition in each of the three sirukumab groups, and none in either placebo group. The counts are 3, 2, 1, 0, and 0, with denominators of 17, 13, 9, 9, and 7. Those observations describe the analyzed participants; they do not, by themselves, establish that the regimens differ or that any difference is statistically reliable.

The registry provides no inferential comparison, confidence interval, or p-value for the endpoint. It specifically notes that values for a two-arm binary comparison were missing or not estimable. As a result, the precision of any apparent contrast cannot be evaluated from the posted analysis. The small, unequal group denominators and the low event counts further limit what can be inferred from the raw counts alone.

The endpoint is a composite of clinical remission, laboratory thresholds, absence of flare, completion of prednisone taper, and no rescue therapy. A count meeting the full definition does not show which component determined outcomes for participants who did not meet it. Component-specific results and detailed missing-data handling are not reported in the registry record.

The study status is terminated, and the record gives no reason for termination. It also does not report whether the planned study phases and follow-up were completed as intended. The registry record therefore does not support conclusions about why the study ended or how the termination affected the results.

These observations should not be interpreted as medical advice or as a definitive judgment about treatment. They are a description of the registered design and posted outcomes. The absence of a reported comparative analysis means that the data presented do not establish a treatment effect, its magnitude, or its precision.

14. Why This Trial Matters Statistically

This study illustrates why the distinction between observed counts and comparative evidence matters. A binary endpoint can be summarized as participants meeting a definition and the number included in each group, but the pattern of counts is not itself an estimate with known precision. Here, the record reports small group denominators and sparse events, while providing no confidence intervals, p-values, or estimable two-arm comparison. Readers can describe the observed counts but cannot assess the uncertainty around a treatment contrast from the posted primary analysis.

The endpoint also illustrates how a composite outcome shapes interpretation. Sustained remission required clinical and laboratory criteria, no flare over a defined period, taper completion, and no rescue therapy. These elements represent more than a status at one visit, but a single composite count does not indicate which requirements most often determined whether participants met the endpoint. Component-level results would be needed to understand that pattern; they are not reported in the registry record.

There is also a notable distinction between the study’s planned and recorded enrollment: the summary described approximately 204 participants, while the record lists enrollment of 161. The reason for the difference is not reported. Combined with the terminated status and lack of a reported termination reason, this makes transparency about recruitment, completion, and analysis particularly relevant to interpretation.

Finally, the trial has several prednisone taper regimens, and the placebo groups do not all use the same taper duration. This means a comparison must be understood in the context of the specific assigned regimen rather than as an isolated comparison of drug versus placebo across otherwise identical conditions. The registry record offers the design and descriptive counts, but not the inferential results needed to resolve those comparisons.

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 registry record does not report the reason the study was terminated or explain whether termination altered enrollment, follow-up, or planned analyses. It reports actual enrollment of 161 and a planned Part A enrollment of approximately 204, but does not explain the difference. The record also does not establish which participants completed Part A or entered the extension phase.

For the primary outcome, the record defines the Intent-to-Treat population as randomized participants who received at least 1 dose, then states that only participants who completed Week 52 or withdrew before 10 Oct 2017 were included in the analysis. Further detail about the relationship between these criteria is not reported. The handling of missing endpoint components and participants without a qualifying Week 52 assessment is also not reported.

The posted primary outcome has few events and small, unequal denominators. No confidence intervals, p-values, or two-arm comparison estimates are available. This limits assessment of precision and makes descriptive differences difficult to interpret as evidence of a treatment contrast. The record does not report component-level primary endpoint outcomes or the method used to verify endpoint components.

The treatment groups also vary in sirukumab schedule and prednisone taper duration. A comparison across groups must account for those differences in regimen. The registry record does not report a multiplicity plan, detailed statistical analysis plan, interim analysis information, or the trial’s sample-size justification. It does not report missing-data sensitivity analyses or the rationale for the posted analysis population. These limitations restrict conclusions to the registered design and the descriptive results available.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis — NCT02531633.
• Registry record last updated 2019-07-31; status last verified 2019-07.
• Results first posted 2019-05-31.
• 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

The registry record describes a Phase 3, randomized, double-blind, parallel-group study of sirukumab and prednisone taper regimens in giant cell arteritis. It lists enrollment of 161, a start date of 2015-10-16, a primary completion date of 2018-03-21, and status as terminated. The reason for termination is not reported.

The primary Part A outcome was the number of participants in sustained remission at Week 52. The posted counts were 3 of 17, 2 of 13, 1 of 9, 0 of 9, and 0 of 7 across the three sirukumab and two placebo groups. No inferential comparison, confidence interval, or p-value is reported for that binary outcome.

The record lists serious adverse events, other adverse events, and numerous secondary outcomes. Interpretation is limited by the small primary-outcome denominators, lack of reported comparative analyses, and missing information about termination, missing data, and multiplicity.