A Pilot Study of KPL-914 in Recurrent Pericarditis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of KPL-914 in Recurrent Pericarditis (NCT03980522), a non-randomized phase 2 study. The primary outcome is Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels.

2. Clinical Question

The registry lists 26 enrolled participants and identifies recurrent pericarditis as the condition under study. Eligibility differed across parts: some groups required symptoms and elevated CRP, another allowed CRP at or below 1 mg/dL alongside MRI-confirmed pericardial inflammation, and other groups involved corticosteroid-dependent disease without symptoms meeting flare criteria. Those differences matter when interpreting group-level results: the parts represent distinct clinical settings rather than interchangeable arms in a controlled comparison.

3. Trial Design

The registry describes a Phase 2, open-label, non-randomized, parallel study of KPL-914. Enrollment was 26, and the study status is completed. The listed start date is 2018-01-24 and the primary completion date is 2019-05-17. Kiniksa Pharmaceuticals (UK), Ltd. is the sponsor. The study purpose was to assess preliminary efficacy and safety in participants with recurrent pericarditis.

Participants were organized into Parts 1 through 5, each with its own eligibility description. Parts 1 and 4 enrolled symptomatic participants with elevated systemic inflammation, defined in the record as CRP above 1 mg/dL; Part 1 concerned recurrent idiopathic pericarditis and Part 4 recurrent PPS. Part 2 concerned symptomatic RIP with CRP at or below 1 mg/dL, attributed in the investigator’s opinion to concomitant medication, and MRI evidence of pericardial inflammation confirmed by an imaging core lab. Parts 3 and 5 enrolled corticosteroid-dependent participants without symptoms that would meet the diagnostic criteria for a flare, in RIP and recurrent PPS respectively.

Because allocation was non-randomized and masking was absent, participants and investigators knew the treatment assignment. The record lists KPL-914 participant groups, not a randomized comparator arm. Differences between parts may reflect their different eligibility criteria and clinical circumstances, so they should not be read as controlled treatment contrasts. Further operational details—including dosing, treatment duration, allocation procedures within the parts, and any protocol deviations—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.

Before assignment: Overall, 26 participants were enrolled in the study; however, only 25 unique participants were included in the analyses, as one participant was enrolled a second time.

Treatment Period

Reasons for not completing this period:

Extension Period

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT) Population: all participants who received at least one dose of study drug. Participants with an assessment at given time point.

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: Safety Population: all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels, measured over Screening Visit 1 (Day -3 to Day 0), Screening Visit 2 (Day -3 to Day 0), Day 0, Baseline (defined as the last non-missing assessment prior to the first study drug administration).

The primary outcome is titled “Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels.” It is a continuous measure reported as a mean with standard deviation, in mg/dL. The listed assessment occasions are Screening Visit 1, Screening Visit 2, Day 0, and baseline. Baseline is defined as the last non-missing assessment before the first study drug administration. The population is the modified Intent-to-Treat (mITT) population: participants who received at least one dose, with an assessment at the relevant time point.

CRP is a marker of systemic inflammation. In general, a continuous measure retains information about the magnitude of individual measurements, while its mean describes the group’s average and its standard deviation describes variation among measurements. Assessing CRP before treatment can characterize the inflammation marker at study entry. It does not, by itself, establish a treatment effect: that requires interpretable outcome values and an appropriate analysis, including a clear account of changes over time and uncertainty.

The registry record does not report the CRP means, standard deviations, or analysis results. It also does not list Parts 3 and 5 in the primary outcome title. The reason for that endpoint scope is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

General statistical context. A mean is the arithmetic average of a set of measurements and gives a summary of its central location. A standard deviation describes how dispersed the measurements are around that average. They answer different questions: the mean concerns the typical level on the measurement scale, while the standard deviation concerns variation among observations. Neither summary, on its own, shows the full distribution or the uncertainty around a treatment-related change.

For this study, the primary outcome is described as a mean with standard deviation for CRP, measured in mg/dL. The registry record does not report the actual means or standard deviations. Without those values, the amount of variation and the average CRP level at the listed time points cannot be assessed from the record.

What is the role of the assessment times?

The endpoint description lists Screening Visit 1, Screening Visit 2, Day 0, and baseline, with baseline defined as the last non-missing assessment before the first study drug administration. Repeated assessments can help characterize a measure at more than one occasion. General statistical context: comparisons across time require a clear definition of which assessments are used, how they are paired or modeled, and how missing measurements are handled. The registry record does not report an analysis model or a numerical comparison across these occasions. It also does not explain how the two screening assessments relate to the other listed time points analytically.

What does the mITT population mean in this record?

The record defines the mITT population for this measure as participants who received at least one dose of study drug and had an assessment at the given time point. This definition ties inclusion to treatment receipt and availability of an outcome measurement at each occasion. General statistical context: an analysis population affects which participants contribute to an estimate. If the participants with observed measurements differ systematically from those without measurements, a complete-case summary may not represent everyone enrolled. The registry record does not report how many measurements were missing at each occasion or whether any method was used to account for missing data.

What can a confidence interval tell a reader?

General statistical context. A confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, while both the estimate and interval are needed to judge the range of effects reasonably compatible with the data under that method. A confidence interval is not a guarantee that the true value lies within its limits, nor does it resolve biases caused by study design or measurement. No confidence interval for the primary CRP outcome is reported in the registry record, so its precision cannot be evaluated.

Why does the study design matter for analysis?

The study is open-label and non-randomized. General statistical context: random allocation can balance measured and unmeasured prognostic characteristics on average across comparison groups, whereas non-random allocation can leave group differences that complicate causal interpretation. Masking can reduce some influences of expectations on assessment or reporting; in an open-label study, those influences cannot be excluded by blinding. Here, the participant groups also have distinct eligibility criteria. Any comparison across those groups would therefore require careful interpretation and adjustment choices, neither of which is detailed in the registry record. The record does not report a randomized comparator group.

How should the planning illustrations be read?

The registry describes sample-size calculations as planning illustrations computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. These are not the trial’s own design calculations, and they are not observed power. General statistical context: planning calculations ask how much information a hypothetical study might need under stated assumptions. Their interpretation depends on the assumed effect, variability, allocation, and analysis method. The registry record does not report its own sample-size justification, or a statistical plan showing that these planning assumptions governed the trial.

Because the primary CRP result is not reported in the record, the observed effect used as the basis for such illustrations cannot be assessed in the registry record. An illustration should not be interpreted as evidence that a particular effect was detected, nor as proof that the completed study had adequate precision.

Why can over-dispersion matter?

General statistical context. Over-dispersion occurs when observed variability is greater than a model assumes. For continuous outcomes, a mismatch between the assumed and actual variability can make standard errors and confidence intervals unreliable if the model does not account for it. The registry record does not report a model for the CRP data, a distributional assessment, or any evaluation of over-dispersion. The term is relevant as a general modeling consideration, not as a reported feature of this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and 24 analyses. When multiple outcomes or analyses are examined, general statistical context is that the chance of at least one apparently positive finding can rise if each is tested without accounting for the multiplicity. A prespecified hierarchy or adjustment method can help interpret a family of tests, but the registry record does not report whether such a strategy was planned or used. It also does not describe which analyses were confirmatory and which were exploratory.

The primary outcome population is defined as mITT participants who received at least one dose and had an assessment at the given time point. This makes the available-data requirement part of the outcome definition. The record does not report missing-measurement counts by occasion, reasons for missingness, imputation methods, sensitivity analyses, or how participants without a given assessment were treated beyond the stated population definition.

General statistical context: missing data can affect an estimate when the probability of a measurement being missing is related to participant characteristics or the unobserved outcome. A complete-case analysis may then be biased, depending on why observations are absent. Imputation and sensitivity analyses can address some assumptions, but they do not remove the need to explain those assumptions. The registry record does not report which approach, if any, was used for the primary outcome.

The record also does not report a statistical analysis plan, test hierarchy, or method for handling multiple time points. Therefore, the nominal interpretation of any individual analysis cannot be assessed from the registry information.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: non-cardiac chest pain (8.3%), subcutaneous abscess (8.3%).

The registry reports serious adverse event counts by participant group, with the number at risk and the number affected. For Part 1, 12 participants were at risk and 2 were affected; for Part 2, 3 were at risk and 0 were affected; for Part 3, 6 were at risk and 0 were affected; for Part 4, 1 was at risk and 0 were affected; and for Part 5, 3 were at risk and 0 were affected. The reported death count was 0 in each group.

For other adverse events, the record reports 12 affected among 12 at risk in Part 1, 3 among 3 in Part 2, 6 among 6 in Part 3, 1 among 1 in Part 4, and 3 among 3 in Part 5. The top listed serious event terms are Non-cardiac chest pain at 8.3% and Subcutaneous abscess at 8.3%.

These counts describe what the registry reports; they do not establish that KPL-914 caused an event. The group sizes differ, and some at-risk counts are small, so the counts should not be treated as precise estimates of event frequency in a wider population. No controlled safety comparison is reported.

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

This study contributes a description of an open-label, non-randomized Phase 2 pilot in recurrent pericarditis, including five groups with differing eligibility criteria and a primary CRP measure for Parts 1, 2 and 4. The registry also records serious and other adverse event counts by group. Those design and reporting details help readers understand what was studied and how the posted safety counts are organized.

However, the primary CRP results are not reported in the registry record. No numerical primary outcome estimate or uncertainty measure is available to support a conclusion about the direction, magnitude, or precision of change. The study’s stated aim of assessing preliminary efficacy and safety is a purpose, not a result. The safety counts are descriptive and cannot, by themselves, attribute events to KPL-914.

The non-randomized allocation, absence of masking, and different eligibility criteria across groups limit causal interpretation. Any observed change in a participant measure could reflect factors other than treatment, and comparisons among the listed groups would not be randomized comparisons. The registry does not report a separate control group or the detailed statistical plan needed to assess how potential confounding was addressed.

General statistical context: a pilot study can provide early descriptive information and help characterize feasibility or variability, but its findings do not automatically generalize beyond the enrolled participants or establish comparative effectiveness. The record does not report details of a sample-size justification. Planning illustrations based on an observed effect should be read as hypothetical design calculations, not as evidence of observed power or a substitute for missing outcome results.

Accordingly, the registry supports a careful account of study design, endpoint definition, and adverse event counts. It does not support a quantitative conclusion about the primary endpoint or a claim that KPL-914 did or did not produce a clinical benefit.

13. Why This Trial Matters Statistically

The study is statistically notable for the way it separates participants into groups based on disease context, symptoms, inflammation markers, corticosteroid dependence, and imaging. Those criteria create clinically distinct cohorts, but they also mean that the parts should not be treated as exchangeable arms. Readers need the eligibility context to understand what each group’s measurements represent.

The primary endpoint is a continuous inflammation marker measured at screening and around treatment initiation. In general, continuous measures can show both a group’s average level and the spread of individual observations. Those summaries can be useful for describing a pilot population and for informing future study planning. In this record, however, the actual CRP values and variability are not reported, so their statistical contribution cannot be evaluated.

The design also illustrates why a treatment label alone does not make a comparison controlled. The study was non-randomized and open-label, with different eligibility definitions across Parts 1 through 5. Any comparison across parts would mix potential treatment-related differences with differences in who qualified for each part. The record does not report a separate control group.

Finally, the record distinguishes descriptive safety counts from comparative evidence. Serious and other adverse events are reported by group, but event counts do not establish causality. The information is relevant to understanding what was recorded during this pilot, while the missing primary outcome results and unreported analysis details constrain broader statistical conclusions.

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.

Several limitations specific to this study affect interpretation. First, the registry record does not report the primary CRP values, standard deviations, change estimates, confidence intervals, or p-values. The stated primary endpoint therefore cannot be evaluated quantitatively from the record. It is not possible to determine the observed level or change in CRP, or the precision of an estimate.

Second, the design is non-randomized and open-label. The record does not describe a separate control group, and each listed group has distinct eligibility criteria. This limits direct comparisons between groups and makes causal attribution difficult. The registry record does not report whether or how potential confounding was addressed.

Third, the primary measure is specified for Parts 1, 2 and 4, while the eligibility descriptions also include Parts 3 and 5. The rationale for the endpoint’s stated scope is not reported in the registry record. The record does not report dosing, treatment duration, the statistical analysis plan, or the sample-size justification.

Fourth, the mITT definition requires at least one dose and an assessment at the relevant time point, but missing-measurement counts and handling methods are not reported. The record lists 6 outcome measures and 24 analyses without reporting a multiplicity strategy or hierarchy. These omissions make it difficult to assess the robustness and confirmatory status of any analysis.

Finally, safety counts are descriptive, with varying group-specific numbers at risk. They do not show whether events were judged related to treatment, and the registry record does not report a controlled safety comparison. These limitations do not negate the value of a pilot description, but they narrow what can be inferred from its posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pilot Study of KPL-914 in Recurrent Pericarditis — NCT03980522.
• Registry record last updated 2021-05-27; status last verified 2021-05.
• Results first posted 2021-05-27.
• 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

NCT03980522 is a completed Phase 2, open-label, non-randomized, parallel pilot study sponsored by Kiniksa Pharmaceuticals (UK), Ltd. It enrolled 26 participants with recurrent pericarditis and evaluated KPL-914 with the stated aim of assessing preliminary efficacy and safety. The listed start date is 2018-01-24 and primary completion date is 2019-05-17.

Participants were assigned to five parts with differing eligibility criteria covering recurrent idiopathic pericarditis and recurrent post pericardiotomy syndrome. The primary outcome concerns mean pretreatment CRP levels for Parts 1, 2 and 4. The registry record does not report the primary outcome values or a detailed statistical analysis plan. It reports serious and other adverse event counts by group and no deaths in the listed groups. The design and reporting support descriptive interpretation, but do not establish a controlled treatment effect.