Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis (NCT02222155), a randomized phase 2 study. The primary outcome is Incidence of Adverse Events.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, phase 2 study of CCX168 in ANCA-associated vasculitis. The registry record describes the trial as double-blind and placebo-controlled, with quadruple masking. Participants were assigned to placebo, CCX168 10 mg, or CCX168 30 mg, each twice daily alongside standard of care. The listed standard-of-care options were cyclophosphamide or rituximab plus glucocorticoids. Each arm description specifies a 12-week treatment period.

The registry lists enrollment of 42. For the primary safety outcome, the posted arm counts were 13 participants in the placebo group, 13 in the 10 mg group, and 16 in the 30 mg group. The safety population comprised participants who were randomized and received at least 1 dose of study drug. The record does not report whether the analysis used any additional population definition or how participants who did not complete treatment were handled.

The primary outcome timeframe was baseline to Day 85. The registry record gives a start date of 2015-02-04 and a primary completion date of 2016-04-24, and lists the study status as completed. The stated aim was to assess the safety and efficacy of two CCX168 dose regimens. Funding source information identifies FDA OOPD. The record does not report the rationale for the enrollment target, the randomization procedure, or the identities of the roles included in quadruple masking.

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

Analysis population for the primary outcome, as defined in the registry: Safety population: The Safety Population included all subjects who were randomized and received at least 1 dose of study drug

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 Incidence of Adverse Events, measured over Baseline to Day 85.

The primary endpoint was the incidence of adverse events, expressed as the count of participants with events, from baseline to Day 85. Its description identifies the focus as overall rates of treatment-emergent adverse events across the study arms. The analysis population was the safety population: randomized participants who received at least 1 dose of study drug.

A participant count is a direct way to describe how many people in each arm experienced at least one event under the endpoint definition. The counts do not, by themselves, describe the number of separate events, their duration, severity, or timing. Those features require additional event-level information, which is not reported in the primary outcome summary. Nor does the count establish that an event was caused by the assigned treatment.

Safety monitoring is important in a trial assessing a new treatment regimen, alongside efficacy outcomes. Comparing the counts across randomized arms can describe the observed safety experience during the stated follow-up. The trial’s primary outcome was safety-focused; the registry record does not identify a primary efficacy endpoint. The results therefore need to be read as short-term safety observations in the reported population, not as a complete account of longer-term risks or benefits.

7. Results Posted in the Registry

• CCX168 10 mg BID Plus Standard of Care: 84.6% (11/13) versus 100.0% (13/13) on control; risk difference -15.4 percentage points (95% CI -35.0 to 4.2), risk ratio 0.85 (0.67–1.07); unadjusted two-proportion z-test p = 0.141.
• CCX168 30 mg BID Plus Standard of Care: 93.8% (15/16) versus 100.0% (13/13) on control; risk difference -6.2 percentage points (95% CI -18.1 to 5.6), risk ratio 0.94 (0.83–1.06); unadjusted two-proportion z-test p = 0.359.

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.

Percent Change From Baseline to Day 85 in BVAS.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CCX168 10 mg BID Plus Standard of Care: mean -95.60 versus -81.80 on control; difference -13.80 (95% CI -27.33 to -0.27), standardized effect d = -0.76; z-test p = 0.046.
  • CCX168 30 mg BID Plus Standard of Care: mean -81.70 versus -81.80 on control; difference 0.10 (95% CI -20.61 to 20.81), standardized effect d = 0.00; z-test p = 0.992.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for CCX168 10 mg BID Plus Standard of Care than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CCX168 30 mg BID Plus Standard of Care and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Day 85 in the VDI

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CCX168 10 mg BID Plus Standard of Care: mean 0.09 versus 0.31 on control; difference -0.22 (95% CI -0.67 to 0.23), standardized effect d = -0.37; z-test p = 0.333.
  • CCX168 30 mg BID Plus Standard of Care: mean 0.14 versus 0.31 on control; difference -0.17 (95% CI -0.62 to 0.28), standardized effect d = -0.29; z-test p = 0.459.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CCX168 10 mg BID Plus Standard of Care and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CCX168 30 mg BID Plus Standard of Care and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists 13 secondary outcome measures, covering disease remission, disease activity, renal response, kidney-function measures, urinary markers, and disability. Detailed numerical results in the record include percentage change in BVAS and change in VDI. The record does not report detailed numerical results for the other listed secondary measures in the information available for this analysis.

Across the two outcomes with numerical results, the posted arm summaries and unadjusted comparisons do not form a single consistent pattern across doses and measures. The findings are exploratory in context: they concern different clinical constructs and scales, and the registry record does not report a unified analysis that combines them. The secondary measures address disease activity or related clinical outcomes, whereas the primary endpoint counts participants with adverse events. They therefore complement the safety result but do not directly confirm or overturn it.

Unadjusted secondary comparisons carry less weight when several outcomes and contrasts are considered. Testing many questions creates more opportunities for apparently notable results by chance, and the registry record does not report a multiplicity adjustment or a hierarchy governing interpretation. The record also does not provide a full statistical analysis plan that would establish which comparisons were confirmatory. A nominal p-value from one secondary comparison should consequently not be treated as conclusive evidence.

The secondary results can help describe the range of outcomes investigated, but they should be interpreted with their uncertainty and reporting limitations in mind. In particular, the absence of detailed numerical results for some listed measures is not evidence that those outcomes were unchanged. Their results and analysis details are not reported in the registry record.

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

• Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
• Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.
• Percent Change From Baseline to Day 85 in BVAS.
• Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85
• Change in Estimated Glomerular Filtration Rate at Day 85
• Percentage Change in Estimated Glomerular Filtration Rate at Day 85
• Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
• Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either contributes to the count as having an adverse event under the endpoint definition or does not. The posted summary gives the number with an event and the number in each arm. This provides a straightforward description, but it does not retain information about recurrent events or event-level timing and severity.

The reported risk difference compares the proportion of participants with an event in a CCX168 arm with the corresponding proportion in the placebo arm. A value below zero indicates a lower observed event proportion in the CCX168 arm; a value above zero indicates a higher observed proportion. The risk difference is expressed on the proportion scale, rather than as a relative comparison. The registry record also reports relative risks, but interpretation of the primary comparison can be grounded in the risk differences and their intervals.

A confidence interval expresses the range of values reasonably compatible with the observed data under the calculation’s assumptions. It communicates uncertainty in a way that a point estimate alone cannot. An interval that includes zero for a risk difference does not establish that the groups are identical; it indicates that the data do not narrowly determine the direction and size of the difference. The width of an interval matters: broad intervals leave more uncertainty about plausible effects.

A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry record gives unadjusted p-values for the primary comparisons. The statistical testing procedure, any covariate adjustment, and any multiplicity adjustment are not reported in the registry record. Consequently, the p-values should not be interpreted as adjusted evidence across all outcomes or comparisons.

The comparisons are unadjusted recalculations from the posted summary statistics. No discrepancy is flagged in the registry record. If the record had indicated a discrepancy, the sponsor’s own analysis would take precedence; that caveat is not activated by the information recorded for this trial. No sponsor-reported primary analysis is listed, so the recalculated contrasts are descriptive statistical comparisons rather than a substitute for an unavailable reported analysis.

Some secondary outcomes are continuous and are summarized using means and standard deviations. A mean describes the central value of the observed changes, while the standard deviation describes variation among observations within an arm. A mean difference compares the two arm means. The standardized effect size, when reported, expresses that difference relative to a pooled standard deviation; it can aid comparison across scales, but does not itself determine clinical importance. These are general interpretations of the measures, not claims about the clinical meaning of a particular scale.

Over-dispersion is a general concern when count data vary more than a statistical model expects. A model that assumes too little variation can understate uncertainty and make evidence appear more precise than it is. The primary outcome is reported as participants with an event, rather than a recurrent-event count. The registry record does not report a model for the primary analysis, so it is not possible to determine whether over-dispersion was assessed or relevant to the sponsor’s analysis.

Planning calculations associated with a continuous secondary outcome use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They illustrate sample sizes under stated fractions of an observed effect. Such calculations are planning illustrations, not observed power, and they do not show that the trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification or statistical plan.

Randomization and masking are design features intended to reduce systematic differences and influence in treatment assignment and assessment. The registry record describes randomization and quadruple masking, but does not give further operational details. Their presence does not eliminate chance imbalance, missing data, or uncertainty in estimates, particularly when groups are limited in size. How these issues were handled analytically is not reported in the registry record.

11. Confidence Intervals and Precision

The primary comparisons are accompanied by confidence intervals for risk differences. For CCX168 10 mg versus placebo, the estimate is -0.154 and the interval runs from -0.35 to 0.042. For CCX168 30 mg versus placebo, the estimate is -0.062 and the interval runs from -0.181 to 0.056. Each interval includes zero, so neither comparison precisely establishes the direction of the difference in the proportion of participants with an adverse event.

The interval limits also show that the results remain compatible with effects in either direction. A point estimate alone would conceal that uncertainty. The intervals should not be read as a range containing a fixed proportion of individual outcomes, and they do not assign probabilities to specific treatment effects. They describe uncertainty under the statistical method used to calculate them; the registry record does not report the method for these primary intervals.

The group counts were limited, and the confidence intervals reflect uncertainty in the comparisons. The p-values are unadjusted: 0.141 for the 10 mg comparison and 0.359 for the 30 mg comparison. They do not supply additional precision or resolve the uncertainty represented by the intervals. The registry record does not report an adjusted analysis, an interval for an adjusted effect, or a prespecified threshold for interpreting these comparisons.

Precision is distinct from clinical importance. Even a narrow interval would not determine whether a difference matters to patients; that requires clinical context and an appropriate definition of meaningful change. Conversely, an uncertain estimate does not prove that no difference exists. These results should therefore be read as limited estimates of the observed short-term safety contrast, rather than as precise evidence of equivalence or a definitive safety advantage.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes and reports comparisons between each CCX168 dose and placebo for the primary safety outcome. It does not report a multiplicity adjustment, a testing hierarchy, or a prespecified rule for controlling the chance of false-positive findings across these questions. The primary p-values are unadjusted, and the available secondary comparisons are also unadjusted. When several outcomes or contrasts are examined, isolated nominal results warrant caution because the overall opportunity for chance findings increases.

The record does not report how missing outcome data were handled, whether any participants were excluded from particular analyses, or whether sensitivity analyses were conducted. The safety population definition is stated: randomized participants who received at least 1 dose of study drug. The registry record does not give further detail on the analysis population for each secondary outcome, or describe imputation, censoring, or other missing-data procedures. Therefore, the effect of missing observations on the reported results cannot be assessed from the record.

The record reports enrollment and the group counts used for the primary outcome, but does not provide a participant-flow account or reasons for any differences between analysis populations. It also does not report the trial’s sample-size justification, interim analyses, or a complete statistical analysis plan. These omissions limit assessment of how closely the reported analyses followed an original plan and whether analytic decisions could have affected interpretation.

These reporting gaps do not establish that a particular bias occurred. They mean that multiplicity, missing-data assumptions, and analysis choices cannot be fully evaluated from the registry record. Secondary findings should be treated as less definitive than a prespecified, fully described analysis with clear handling of multiple comparisons and missing observations.

13. 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: methemoglobinemia (7.7%), gangrene (7.7%), neutropenia (7.7%), cellulitis staphylococcal (7.7%), abscess limb (7.7%).

The serious adverse event summary reports 3 affected participants among 13 at risk in the placebo arm, 2 among 13 in the CCX168 10 mg arm, and 4 among 16 in the CCX168 30 mg arm. The registry record reports no deaths in these groups. These are participant counts for serious adverse events, distinct from the primary outcome’s broader count of participants with any adverse event.

The record lists Methemoglobinemia, Gangrene, Neutropenia, Cellulitis staphylococcal, Abscess limb, and Perirectal abscess among the top serious adverse event terms, each reported as 7.7%. The available information does not specify an arm attribution for each listed term, so those terms should not be assigned to a particular treatment group.

Counts from groups of this size are descriptive and leave substantial uncertainty about comparative risk. The registry record does not report event-level timing, recurrence, or a causal assessment for these serious events. An event occurring during a trial does not by itself establish that study treatment caused it. The figures should be read as the recorded safety experience during the trial, not as a definitive ranking of the regimens’ safety.

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

The primary result describes how many participants in each randomized arm were recorded as having an adverse event over baseline to Day 85. The posted counts were 13 for placebo plus standard of care, 11 for CCX168 10 mg plus standard of care, and 15 for CCX168 30 mg plus standard of care. The unadjusted risk-difference intervals include zero for both dose comparisons, leaving uncertainty about the direction and size of any difference.

These findings do not establish that CCX168 reduces adverse events, increases adverse events, or has the same safety profile as placebo. They also do not demonstrate efficacy. The study’s stated aim included safety and efficacy, but the primary outcome is safety-focused. Secondary disease activity and renal outcomes are separate questions and do not convert the safety counts into evidence of treatment benefit.

The result is limited to the population and observation period described in the registry record. The primary timeframe ends at Day 85, and each arm was described as receiving treatment for 12 weeks. The data do not establish what might occur with longer treatment or follow-up. The record also does not provide all details needed to assess missing data, analysis choices, or how the reported comparisons relate to a prespecified statistical plan.

Statistical uncertainty and clinical importance are different. The estimates and intervals describe the observed data and their uncertainty; determining the practical importance of a difference would require clinical context that is not reported in the registry record. A non-definitive comparison is not proof of no difference, and a numerical difference is not proof of a causal treatment effect. The appropriate conclusion is descriptive: adverse events were recorded in the reported numbers of participants, while comparative safety remains uncertain.

15. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical biostatistics: a safety endpoint may be reported as a simple participant count, while the statistical comparison still depends on the denominator, the effect measure, and its uncertainty. The risk difference expresses the contrast in absolute terms, and its confidence interval communicates how much uncertainty remains around that contrast. Looking only at the arm counts or the point estimate would give an incomplete picture.

It also demonstrates why a randomized design does not guarantee a precise estimate. Randomization supports a fair comparison in expectation, while limited group sizes can still leave substantial uncertainty in a particular trial. The intervals around both primary comparisons include zero, and the registry record does not report a sponsor analysis or full testing plan that would give additional context.

The trial’s primary outcome and secondary outcomes answer different questions. A count of participants with adverse events is not interchangeable with measures of disease activity, renal response, or disability. Considering these outcomes together requires attention to their distinct meanings and to multiplicity: a collection of unadjusted comparisons should not be treated as a set of independent confirmatory conclusions.

Finally, registry reporting determines what can be assessed. Details about missing data, the sample-size rationale, interim analyses, and the statistical plan are not reported in the registry record. Recognizing those limits is part of sound interpretation, not a judgment that the analyses were necessarily inappropriate. The trial provides short-term safety observations and exploratory secondary information, while leaving comparative conclusions uncertain.

16. 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 outcome is based on participant counts over baseline to Day 85. This is a short observation window for judging safety, and the registry record does not provide longer-term follow-up results. The arm groups were limited in size, which is reflected in the uncertainty around the reported comparisons. The findings should not be generalized beyond the population and follow-up described without additional evidence.

The primary endpoint summary does not describe the number, duration, severity, or timing of separate adverse events. The registry record provides a serious adverse event summary and a list of top terms, but the available information does not assign each listed term to an arm. It also does not report a causal assessment. These limits prevent a detailed comparison of event patterns or attribution.

The record does not report the sample-size justification, the sponsor’s analysis of the primary endpoint, or the full statistical analysis plan. It also does not describe missing-data handling, interim analyses, or multiplicity control. Those omissions constrain assessment of precision, analytic choices, and the strength of secondary findings. The presence of multiple listed secondary outcomes makes the absence of a reported multiplicity approach particularly relevant when interpreting isolated comparisons.

These are limitations of what the registry record reports, not evidence that a specific flaw occurred. The results remain useful as a description of the recorded experience in this completed phase 2 study, but the record alone does not support definitive comparative safety or efficacy conclusions.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis — NCT02222155.
• Registry record last updated 2025-03-13; status last verified 2025-03.
• Results first posted 2023-08-16.
• 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.

20. Record Summary

The registry record describes a completed, randomized, parallel, quadruple-masked, placebo-controlled phase 2 trial of CCX168 in ANCA-associated vasculitis. It lists enrollment of 42 and a treatment period of 12 weeks. The primary safety outcome counted participants with adverse events from baseline to Day 85 in the safety population, defined as randomized participants who received at least 1 dose of study drug.

The posted counts were 13 in the placebo arm, 11 in the CCX168 10 mg arm, and 15 in the CCX168 30 mg arm. The unadjusted risk-difference intervals include zero for both comparisons. Serious adverse event counts were also reported, with no deaths recorded. Secondary outcomes covered disease activity, renal measures, and disability, but detailed numerical results are not reported in the registry record for all listed outcomes.

The record does not report a full statistical plan, sample-size justification, multiplicity adjustment, or missing-data procedures. The primary results therefore describe short-term safety observations while leaving uncertainty about comparative effects and some analytic details.