KPL-301 for Subjects With Giant Cell Arteritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for KPL-301 for Subjects With Giant Cell Arteritis (NCT03827018), a randomized phase 2 study. The primary outcome is Time to Flare by Week 26.

2. Clinical Question

The trial addressed whether the time-to-flare experience differed between the two randomized groups while participants followed a corticosteroid taper. It did not compare mavrilimumab with no corticosteroid treatment: both groups received the taper as part of their assigned regimen. The registry identifies the study as a randomized, double-blind, placebo-controlled Phase 2 trial in giant cell arteritis, with a parallel-group model and quadruple masking.

The primary outcome counted time from randomization to the first flare within the 26-week period. A flare required an elevated inflammatory marker, defined as CRP of 1 mg/dL or greater and/or ESR of 30 mm/h or greater, together with at least one qualifying GCA-related sign, symptom, or new or worsening imaging abnormality. Independent adjudication was used to assess the event. The primary analysis therefore concerns the timing of the first defined flare, rather than simply the proportion of participants with any symptom or a laboratory-marker change alone.

The registry record reports 70 enrolled participants: 42 in the mavrilimumab group and 28 in the placebo group for the primary outcome. The result describes this trial population and its analysis; how broadly it applies beyond that population is not established by the registry result alone.

3. Trial Design

This was a randomized, double-blind, placebo-controlled Phase 2 study with a parallel-group model and quadruple masking. The registry names Kiniksa Pharmaceuticals, Ltd. as sponsor and lists giant cell arteritis as the condition. Enrollment was 70. The study began on 2018-09-20, primary completion was 2020-08-13, and its status is completed.

Participants were assigned to mavrilimumab or placebo. The mavrilimumab regimen was 150 mg every other week by subcutaneous injection; the placebo regimen was also administered every other week by subcutaneous injection. Each was co-administered with a 26-week corticosteroid taper. The registry describes the primary objective as evaluating efficacy and safety of mavrilimumab versus placebo, with the taper, for maintaining sustained remission for 26 weeks in participants with new onset or relapsing/refractory GCA. The posted primary outcome, however, is time to flare by Week 26.

The primary outcome analysis used the modified Intent to Treat population. This included randomized participants who received at least 1 dose of assigned study treatment and had at least 1 assessment during the double-blind treatment period. The primary-outcome arm counts were 42 for mavrilimumab and 28 for placebo. Other outcome analyses have different arm counts, so their analysis populations or available observations should not be assumed to match the primary analysis population exactly.

The registry lists 10 outcome measures and 10 analyses. Nine secondary outcomes are posted. They include sustained remission, timing of elevated ESR or CRP, clinical or imaging indicators, cumulative corticosteroid dose, and outcomes at completion of the taper. The original protocol’s sample-size justification, detailed randomization procedures, and original statistical design assumptions are 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: Modified Intent to Treat (mITT) Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

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 Time to Flare by Week 26, measured over Week 26.

The primary endpoint was time to flare by Week 26, measured in weeks from randomization to the date of the first flare within the 26-week period. A flare was assessed by independent adjudication. The definition combined an inflammatory-marker threshold—CRP of 1 mg/dL or greater and/or ESR of 30 mm/h or greater—with at least one qualifying feature attributed to GCA. These features included specified cranial or extracranial symptoms and new or worsening angiographic abnormalities on MRI, CT/CTA, PET-CT, or ultrasound.

Time-to-event outcomes retain information about when an event occurs, rather than treating all events within follow-up as interchangeable. General statistical explanation: Kaplan-Meier methods estimate the event-free experience over time while accounting for participants whose event time is not observed by the end of follow-up. A median time is the time by which half of the estimated group has experienced the event, if the data support estimating that point. A median may not be estimable within the follow-up window for an arm; the registry’s mavrilimumab median value and interval limits are not reported in the registry record.

Using time to first flare is relevant to a question about how long participants remain without a qualifying flare during the taper period. It does not, by itself, describe the number of later flares, their duration or severity, or the full course of disease after the first event. Those questions require other outcomes and information beyond this endpoint.

7. Results Posted in the Registry

• Mavrilimumab vs Placebo: hazard ratio 0.38 (95% CI 0.15–0.92), reported p = 0.026 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Sustained Remission Rate at Week 26

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Mavrilimumab: 83.3% (35/42) versus 50.0% (14/28) on control; risk difference 33.3 percentage points (95% CI 11.7 to 55.0), risk ratio 1.67 (1.12–2.47); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Mavrilimumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Mavrilimumab vs Placebo: hazard ratio 0.51 (95% CI 0.27–0.95), reported p = 0.028 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Mavrilimumab vs Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Elevated C-Reactive Protein (CRP) by Week 26

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Mavrilimumab vs Placebo: hazard ratio 0.43 (95% CI 0.19–0.98), reported p = 0.038 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Mavrilimumab vs Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover several aspects of disease activity and the taper period: sustained remission, timing of elevated inflammatory markers, clinical or imaging signs, cumulative corticosteroid dose, and outcomes among participants completing the taper. Collectively, these outcomes broaden the description beyond the primary time-to-first-flare endpoint. The available results point in a direction generally compatible with the primary comparison, but they do not all measure the same construct or use the same statistical scale.

Sustained remission at Week 26 is a binary outcome, whereas time to elevated ESR and time to elevated CRP are time-to-event outcomes. The clinical or imaging measures and corticosteroid-related outcomes address still other questions. Similar direction across related outcomes can provide context for the primary result, but it does not make the outcomes interchangeable or independently confirm the same estimand. The primary result specifically concerns the timing of a first adjudicated flare under the registry definition.

There are 9 posted secondary outcomes, and the registry reports 10 outcome measures and 10 analyses overall. The registry record does not report whether the secondary analyses were adjusted for multiple comparisons, how outcome hierarchy was defined, or whether all planned secondary analyses are posted. When multiple outcomes are examined, some apparently notable results may arise by chance even if no true effect exists for the corresponding outcome. General statistical explanation: multiplicity adjustment or a pre-specified testing hierarchy can help control the risk of false-positive conclusions across a family of tests. Without reported adjustment details, secondary p-values should be treated as exploratory or supportive rather than as a set of independent confirmatory findings.

Secondary results can help characterize the pattern and consistency of observed outcomes, but their evidential weight is lower when the analysis plan and multiplicity handling are not reported. They also cannot resolve limitations of the primary analysis or establish effects on outcomes not measured. Interpretation should account for the different populations and available arm counts across outcomes, as well as the uncertainty reflected in each estimate.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Sustained Remission Rate at Week 26
• Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26
• Time to Elevated C-Reactive Protein (CRP) by Week 26
• Time to Signs/Symptoms of Giant Cell Arteritis (GCA) or New or Worsening Vasculitis on Imaging by Week 26
• Cumulative Corticosteroid Dose at Week 26
• Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal ESR
• Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level
• Percentage of Participants Who Completed the 26-week Corticosteroid Taper and Who Had No Signs or Symptoms of GCA Nor New or Worsening Vasculitis by Imaging by Week 26

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is a time-to-event analysis. Each participant’s event time was measured from randomization to the first flare within the 26-week period. Participants who did not have a recorded flare during the analyzed period may contribute information up to the point their event status is no longer observed; the registry record does not describe the precise censoring rules used. General statistical explanation: time-to-event methods are designed to use both the timing of observed events and the period for which participants are known to be event-free, rather than requiring every participant to have an event.

What does Kaplan-Meier estimation contribute?

The registry says Kaplan-Meier methods were used to estimate survival functions for each treatment arm. In this context, “survival” refers to remaining free of the defined flare, not survival from death. General statistical explanation: a Kaplan-Meier curve estimates the probability of remaining event-free over time, accounting for censoring under its assumptions. It can be used to estimate a median event time when the estimated event-free probability reaches the point corresponding to half the group having experienced the event. The placebo median was 25.1 weeks. The mavrilimumab median value is not reported in the registry record, so the arm’s median cannot be quoted from the posted result.

How should the hazard ratio be read?

The reported hazard ratio compares the event hazard in the mavrilimumab group with the event hazard in the placebo group. Its estimate was 0.38, with a 95% confidence interval of 0.15 to 0.92. A value below 1 indicates a lower estimated event hazard in the first group relative to the comparator during follow-up. General statistical explanation: a hazard ratio is a relative comparison of event rates at times during follow-up; it is not a ratio of median times, nor does it directly state the probability that an individual will experience a flare. Its interpretation also depends on the time-to-event model and assumptions. The registry record does not report enough information to evaluate all such assumptions or diagnostics.

The log-rank test compares the event-time experience across groups using information over follow-up. The registry reports a log-rank p-value of 0.026. General statistical explanation: a p-value measures how compatible the observed data are with a specified null model, under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The p-value should be considered alongside the hazard-ratio estimate and confidence interval, rather than used as a stand-alone conclusion.

What does the flare definition mean for analysis?

The endpoint did not define flare by a laboratory marker alone. It required CRP of 1 mg/dL or greater and/or ESR of 30 mm/h or greater together with at least one qualifying sign, symptom, or imaging finding attributed to GCA. The combination creates a specific event definition, and independent adjudication was part of its assessment. This makes the result specific to the registry’s operational definition; different definitions could identify different event times. The record does not report further details about adjudication procedures or how disagreements were handled.

For the sustained remission secondary outcome, the posted registry analysis reports a difference in proportions using a normal approximation. The stated arm estimates were 83.2% for mavrilimumab and 49.9% for placebo, with respective 95% confidence intervals of 67.9 to 91.6 and 29.6 to 67.3. General statistical explanation: a difference in proportions expresses a group contrast on an absolute scale, while a hazard ratio is a relative time-to-event measure. The two effect measures are not interchangeable. The registry also includes a simple unadjusted recalculation for this binary outcome; the sponsor’s reported analysis is described separately.

The original statistical analysis plan, any model checks, detailed censoring specifications, and the trial’s original sample-size assumptions are not reported in the registry record. General explanation of method does not fill those reporting gaps. The listed planning illustrations are based on observed effects and stated assumptions; they do not establish what assumptions were used when the trial was designed.

11. Confidence Intervals and Precision

The primary hazard-ratio estimate is 0.38, with a 95% confidence interval from 0.15 to 0.92. A confidence interval describes a range of values compatible with the data and the statistical method, subject to its assumptions. The interval indicates uncertainty around the estimate: values toward its lower and upper limits represent materially different relative hazard estimates. Its upper limit remains below 1, but the interval is not narrow enough to specify a single precise effect.

The placebo median time to flare was 25.1 weeks, with a lower 95% confidence limit of 16.0 weeks. The upper confidence limit is not reported in the registry record. The mavrilimumab median and its interval limits are also not reported in the registry record. Consequently, the precision of the median-time estimate cannot be compared across both groups from the posted values. An unreported limit should not be treated as a specific number or as proof that the estimate is exact.

The primary analysis included 42 mavrilimumab participants and 28 placebo participants. The number of participants is not the same as the number of observed flares, and the event count is not reported in the registry record. General statistical explanation: precision in a time-to-event comparison depends especially on the number and timing of events, as well as on the analysis and follow-up, not only on the enrollment count. The registry record does not give enough detail to reconstruct the amount of information contributed by each participant.

The secondary remission estimates also have uncertainty. Their 95% confidence intervals are 67.9 to 91.6 for mavrilimumab and 29.6 to 67.3 for placebo. These intervals convey uncertainty in each group estimate; they do not, by themselves, provide the interval for a between-group difference. The sponsor-reported difference analysis has its own 95% confidence interval, 10.7 to 55.8. Confidence intervals should be read with the estimand and method in mind, rather than as guarantees about the true value or as statements about individual outcomes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations use the observed effect as a reference and show planning needs for different fractions of that effect. The binary-outcome illustrations are expressed as participants per arm. The time-to-event illustrations are expressed as total events, not participants. For those event-based illustrations, the number refers to events across the two groups combined; it is not a target enrollment count. Turning an event target into a participant count would require assumptions about event rates and follow-up that are not given in the registry record.

The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For time-to-event outcomes, the illustrations use the Schoenfeld approach and count total events. For the other outcomes, the figures are participants per arm. The original trial’s own sample-size justification and design assumptions are not reported in the registry record; these calculations are planning illustrations based on the observed result, not a reconstruction of the trial’s original design.

The 80% power column describes the planning number of events or participants that would give an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column describes the corresponding target for a 90% chance. These are conditional planning quantities, not guarantees that a future study will detect an effect. The illustrations show that planning for a smaller fraction of the observed effect requires more participants or events than planning for the full observed effect.

These figures are not observed power. They should not be used to infer that the completed trial was adequately or inadequately powered from its results alone. In a time-to-event setting, required events and required enrollment are distinct: enrollment would depend on how often events occur and how long participants are followed. Those additional planning inputs are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 0.380, so ln(HR) = -0.9676.
2. d = 4 × (1.96 + 0.842)² / [ln(0.380)]² = 33.5, rounded up to 34 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 0.38                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(3827018)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 34 (80% power), 45 (90% power)
 75% of observed effect: events = 60 (80% power), 80 (90% power)
 50% of observed effect: events = 135 (80% power), 180 (90% power)
Simulated power with 34 events: 0.801 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The registry’s reported primary analysis gives a hazard ratio of 0.38, a 95% confidence interval of 0.15 to 0.92, and a log-rank p-value of 0.026. The corresponding reported-analysis values are the figures to use when describing the sponsor’s primary result. The primary comparison is a time-to-event analysis; it should not be replaced by a calculation from arm medians, especially because the mavrilimumab median is not reported in the registry record.

For sustained remission, the registry reports a sponsor analysis using a normal approximation. It gives a difference in proportions of 33.3, with a 95% confidence interval of 10.7 to 55.8 and p = 0.004. A separate simple unadjusted recalculation from the posted arm summaries gives a risk difference of 0.333, a confidence interval from 0.117 to 0.550, and p = 0.003. These calculations are not identical in displayed scale or method. They should be understood as separate analyses rather than combined into one estimate.

The registry marks the record’s discrepancy flag as false. The recalculation is not an alternative sponsor analysis and does not add adjustment for any other variables. For interpretation of the trial, the sponsor’s reported analysis remains the relevant reported result; the recalculation is only a transparent, unadjusted check based on the posted summaries. The registry does not report further detail explaining the exact computational choices behind the remission comparison.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and multiple secondary outcomes, but it does not report a multiplicity-adjustment plan, an ordered testing hierarchy, or whether the secondary outcomes were intended to support formal confirmatory claims. It is therefore not possible to determine from the record whether the reported secondary p-values account for testing several outcomes. General statistical explanation: when many hypotheses are tested, the chance of at least one apparently unusual result can rise; methods for handling multiplicity address that issue but may affect how individual results are interpreted. The primary p-value should not be treated as though it automatically resolves multiplicity across all outcomes.

The record defines the modified Intent to Treat population for the primary analysis as randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment during the double-blind treatment period. This differs from an analysis of every randomized participant regardless of treatment receipt or assessment. The registry does not report the full rationale for this population definition or results for a separate full randomized population.

Arm counts differ across posted outcomes. For example, the primary analysis lists 42 participants for mavrilimumab and 28 for placebo, while some secondary analyses have smaller counts. The registry does not explain the reasons for all differences in available counts. It also does not report a detailed missing-data strategy, whether missing observations were imputed, or sensitivity analyses addressing missing outcomes. Those details matter because the way missingness is handled can influence estimates, especially when outcomes are measured over time.

The registry provides the flare definition and says that flare was assessed by independent adjudication, but further operational detail is not reported in the registry record. The exact censoring rules, handling of protocol deviations, and analysis-plan amendments are also not reported in the registry record. These are limitations of what can be assessed from the registry entry; they do not establish that the trial lacked such procedures. The original statistical analysis plan is not reported in the registry record, so the degree to which analyses followed pre-specified decisions cannot be judged from this information alone.

16. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal haemorrhage (3.6%), oedema peripheral (3.6%), pulmonary fibrosis (3.6%), hypertrophic cardiomyopathy (2.4%), dementia (2.4%).

The registry reports serious adverse events in 2 of 42 participants at risk in the mavrilimumab group and 3 of 28 in the placebo group. It reports other adverse events affecting 33 of 42 and 25 of 28 participants, respectively. No deaths were reported in either group. These are participant counts, not a comparison adjusted for exposure time or other factors, and they should be read as descriptive safety summaries from this trial.

The registry lists gastrointestinal haemorrhage, oedema peripheral, and pulmonary fibrosis among the top serious-event terms, each at 3.6%; hypertrophic cardiomyopathy and dementia are listed at 2.4% each. The record does not identify an arm for these term-specific percentages in the registry entries, so they should not be attributed to either treatment group. The registry also does not provide enough detail to evaluate event timing, duration, recurrence, or causal attribution.

With the number of participants enrolled and the small serious-event counts reported, these figures cannot establish whether a difference in serious-event risk exists. They also do not prove that an event was caused by assigned treatment. The absence of reported deaths in this study does not establish the absence of risk beyond the trial’s observed participants and follow-up.

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

The primary result describes a difference in time-to-first-flare experience between randomized groups receiving mavrilimumab or placebo, with both groups also receiving a 26-week corticosteroid taper. The reported hazard ratio was 0.38, with a 95% confidence interval of 0.15 to 0.92 and a log-rank p-value of 0.026. The result is evidence of a group difference under the registry’s endpoint definition and analysis, while the confidence interval shows that the magnitude remains uncertain.

The finding does not mean that every participant receiving mavrilimumab remained flare-free, or that every participant receiving placebo experienced a flare. A hazard ratio is a group-level relative time-to-event measure, not an individual prediction. Nor does the result show that mavrilimumab alone, without a corticosteroid taper, would have the same observed relationship: both assigned regimens included the taper.

The result also does not answer every question about disease control. It concerns first flare through Week 26 as defined by the registry, not all subsequent disease activity, long-term outcomes, quality of life, or every possible safety outcome. The posted median for placebo was 25.1 weeks, with a lower confidence limit of 16.0 weeks; the mavrilimumab median is not reported in the registry record. That limitation prevents a direct median-time comparison from the values posted.

The trial was a Phase 2 study with 70 enrolled participants, and the primary analysis included 42 in the mavrilimumab arm and 28 in the placebo arm. The estimate should be interpreted in that setting and with the reported uncertainty. The registry does not provide the original sample-size justification, full missing-data strategy, or detailed multiplicity plan, so those aspects cannot be used to strengthen or weaken the result beyond what is documented. The result does not by itself establish a broader treatment recommendation or settle how the regimen performs in populations or settings not represented in this trial.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of endpoint and effect measure matters in clinical research. The primary question was about time to first flare, so the registry used a time-to-event analysis rather than reporting only a count of participants with a flare. That approach preserves information about timing and uses follow-up information from participants whose event status may not be observed through the full period. The reported result is therefore a hazard ratio and a log-rank test, not a simple difference in event proportions.

The definition of flare also combines laboratory thresholds with clinical or imaging evidence. That combination distinguishes the primary endpoint from a measure based only on ESR or CRP. The secondary outcomes separately examine elevated markers, remission, and other clinical or taper-related measures. These related but non-identical outcomes demonstrate how trial conclusions depend on how an outcome is defined and when it is assessed.

The confidence interval is central to interpretation. The hazard-ratio estimate of 0.38 is accompanied by a 95% interval from 0.15 to 0.92, making clear that the data are compatible with a range of relative effects. The p-value alone would not convey that range. The placebo median is reported, but the mavrilimumab median is not reported in the registry record, another reason to distinguish the information contained in a relative time-to-event estimate from the information in arm-specific medians.

The record also illustrates a reporting challenge: outcome-specific analysis counts vary, while detailed missing-data and multiplicity methods are not reported. Separating the sponsor’s reported analysis from a simple unadjusted recalculation helps avoid treating distinct statistical procedures as interchangeable. Together, these points support careful reading of effect measures, uncertainty, analysis populations, and the limits of registry reporting.

19. 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 result is based on a Phase 2 trial with 70 enrolled participants, and the primary analysis lists 42 participants in the mavrilimumab group and 28 in the placebo group. The registry does not report the number of observed flares, so the event information supporting the hazard ratio cannot be assessed directly from the posted summary. The primary median and confidence limits for mavrilimumab are not reported in the registry record, and the upper confidence limit for the placebo median is also not reported.

The registry record does not report the original sample-size justification or the trial’s original design assumptions. The sample-size illustrations based on observed effects do not fill this gap. The detailed statistical analysis plan, missing-data methods, censoring rules, and multiplicity strategy are not reported in the registry record. Without those details, it is difficult to assess the sensitivity of findings to analytic choices or the confirmatory status of the secondary analyses.

Outcome-specific participant counts differ, and reasons for all such differences are not reported. The primary analysis population excludes randomized participants who did not receive at least 1 dose or did not have at least 1 double-blind assessment, according to the registry definition. The posted result therefore describes that modified population rather than every randomized participant regardless of treatment or assessment.

The results apply to the specified flare definition, Week 26 period, and regimens in which both groups received a corticosteroid taper. The registry summary does not establish whether results would be similar under a different taper or longer follow-up. Serious adverse-event counts are small and descriptive, and the listed term-specific percentages are not linked to an arm in the registry entries. These constraints limit the conclusions that can be drawn about comparative safety and about less common outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: KPL-301 for Subjects With Giant Cell Arteritis — NCT03827018.
• Registry record last updated 2023-10-23; status last verified 2023-10.
• Results first posted 2023-10-17.
• 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.

23. Record Summary

NCT03827018 is a completed, randomized, double-blind, placebo-controlled Phase 2 study of mavrilimumab in giant cell arteritis. The parallel-group trial enrolled 70 participants and compared mavrilimumab, 150 mg every other week by subcutaneous injection, with placebo; both were given alongside a 26-week corticosteroid taper.

The primary endpoint was time to first independently adjudicated flare through Week 26. The modified Intent to Treat primary analysis included 42 mavrilimumab participants and 28 placebo participants. The registry reports a hazard ratio of 0.38 (95% CI 0.15 to 0.92; log-rank p = 0.026). The placebo median time to flare was 25.1 weeks; the mavrilimumab median is not reported in the registry record.

The record also posts secondary outcomes and descriptive adverse-event counts. Detailed original sample-size assumptions, missing-data methods, and multiplicity handling are not reported in the registry record.