A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome (NCT03703908), a na phase 2 study. The primary outcome is The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20%.

2. Clinical Question

The clinical question concerns whether participants treated with CCX140-B had a reduction in urine protein-to-creatinine ratio (UPCR) of at least 20% from baseline to week 12. The registry lists this as the primary outcome, measured as a count of participants. It also lists secondary outcomes concerning remission, changes in UPCR and estimated glomerular filtration rate (eGFR), and time to rescue therapy.

This is a descriptive question about the participants enrolled in this study, not a randomized comparison of CCX140-B against another treatment or a control condition. The registry record does not post the number of participants who met the primary endpoint, nor does it report an effect estimate or uncertainty interval. Thus, the endpoint is defined, but the posted record does not provide the result needed to answer the question.

The study's secondary outcomes broaden the questions beyond the primary threshold. They include partial or complete remission through week 12 and through the end of treatment, complete and partial remission during treatment, time to complete remission, change in UPCR over time, time to rescue therapy, and changes in eGFR calculated using cystatin C and creatinine equations. These are outcome definitions, not evidence that a particular response occurred.

3. Trial Design

The registry describes a phase 2, open-label study of CCX140-B in participants with primary FSGS and nephrotic syndrome. The design is sequential and involves intra-subject dose escalation. Participants initially received active study medication at 5 mg twice daily; the dose was to increase stepwise up to 15 mg twice daily. No separate placebo, standard-care, or other comparator arm is listed.

Enrollment is reported as 5 participants. The record gives a start date of 2018-10-01 and a primary completion date of 2020-06-24, and lists the study status as terminated. The reason for termination is not reported in the registry record. The dates and status do not establish how long any individual participant was treated or whether each participant completed the planned dose escalation.

Because the study has no listed control group and is not a randomized comparison, changes during treatment cannot by themselves distinguish a treatment-associated pattern from changes that might occur over time for other reasons. The open-label design also means the registry does not describe masking of participants or study personnel. Allocation is listed as not applicable, consistent with the absence of separately allocated comparison arms.

The primary outcome is a count of participants whose UPCR fell by at least 20% from baseline to week 12. The registry also lists secondary outcomes related to remission, UPCR, eGFR, and rescue therapy. It reports 14 outcome measures, but the registry record lists no analyses. As a result, it does not provide participant-level completion information, outcome counts, or statistical estimates with which to assess the planned questions.

The registry record does not report the reason for choosing the dose-escalation steps, the intended treatment duration for each participant, or a detailed analysis plan. It also does not report a sample-size justification. The planning illustrations associated with the results use assumptions that are not the same as the design of this study: they describe equal allocation between two arms, whereas this record describes a sequential study without a separate comparator arm. Those illustrations should not be read as a description of the trial's enrollment plan.

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

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 The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20%, measured over Baseline to week 12.

The primary endpoint is the number of participants with a reduction in UPCR of at least 20% between baseline and week 12. UPCR relates the amount of protein measured in urine to urine creatinine. The endpoint converts a change in this measurement into a yes-or-no participant outcome: a participant either meets the stated reduction threshold by the specified time or does not.

Threshold outcomes can be easier to interpret than a group average alone because they describe how many participants crossed a prespecified response boundary. They also make the definition of response explicit: the registry's threshold is a reduction of at least 20%, and the assessment interval is baseline to week 12. This description does not show how many participants met the threshold. That count is not reported in the registry record.

UPCR is also included among the secondary outcomes as a measure tracked over time, and remission outcomes are listed separately. Those outcomes should not be treated as interchangeable with the primary endpoint. A participant may or may not meet the primary reduction threshold, while remission is a distinct outcome with its own registry definitions. The operational criteria for partial and complete remission are not reported in the registry record.

For a count endpoint, the result would ordinarily be presented as the number of participants meeting the definition, interpreted in relation to the number assessed. With enrollment of 5 participants, the small study size would make each participant's outcome important to the descriptive result. However, the registry does not report the number assessed at week 12 or the endpoint count, so neither the response pattern nor its precision can be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level endpoint: each participant either has a UPCR reduction of at least 20% from baseline to week 12 or does not. The registry describes the result as a count of participants. For this kind of endpoint, a complete report would ordinarily state both the count meeting the definition and the number assessed. The registry record gives neither figure, so the primary result cannot be reconstructed from the posted information.

What does a threshold endpoint represent?

A threshold endpoint turns a continuous measurement into a response classification. UPCR can vary across a range of values; applying a stated cutoff makes the outcome easier to summarize as the number meeting a criterion. This can aid interpretation, but the cutoff does not capture every feature of a participant's measurement. A participant just short of the boundary and a participant with little change may both fall outside the response category, even though their measurements differ. The registry's primary outcome is specifically the count meeting its stated threshold, not an average change in UPCR.

The registry separately lists change in UPCR over time and remission outcomes. Those measures address different questions. A continuous change outcome describes the trajectory or amount of change, while remission categories classify response according to their own definitions. The remission criteria and the planned summary methods for continuous UPCR change are not reported in the registry record. The measures should therefore be interpreted according to their separate definitions rather than treated as alternative labels for the primary endpoint.

Why does the design matter for the analysis?

A randomized comparison estimates a contrast between groups formed under a defined allocation process. This study is described instead as sequential and intra-subject, with dose escalation, and no separate comparator group. That means any reported within-study change would be a description of participants across the study period, not a randomized estimate of the difference between CCX140-B and a control condition. The open-label design also means that masking is absent according to the registry.

General statistical interpretation distinguishes an observed change from a causal treatment effect. A measured difference from baseline can coincide with treatment, but without a suitable comparison it can also reflect other influences, such as natural variation over time or changes in care. This general caution does not imply that any particular alternative explanation occurred in this study. The registry record does not report methods designed to separate those possibilities.

How should uncertainty be described?

A confidence interval is a statistical range used to show the uncertainty around an estimate under a specified method. It communicates more than a single point estimate: wider intervals indicate less precision, while narrower intervals indicate greater precision for that estimate and method. For a binary response count, uncertainty depends on the number assessed and the number meeting the definition. Neither the count nor the assessed denominator is reported, and no interval is posted.

A p-value addresses how compatible data are with a specified statistical model or null hypothesis; it is not the probability that a treatment works or that a finding is true. No p-value or inferential analysis is reported for the primary outcome. Because the record lists 0 analyses, there is no posted statistical test to interpret. The absence of a p-value is not evidence of no effect; it means the registry entry does not provide that analysis.

What do the planning assumptions describe?

The planning illustrations associated with the results use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They express the target effect as a stated fraction of an observed effect. For time-to-event outcomes, the stated approach concerns a total number of events; for other outcomes, it concerns participants per arm. These are planning assumptions, not the design of the registry study, which is sequential and has no separate comparator arm.

Sample-size planning asks how many participants or events might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. Such calculations depend on the assumed effect, variability or event rate, allocation, and analysis method. If the assumed effect is not supported by an estimate relevant to the design, the resulting illustration may not be informative for that design. The registry record does not report a sample-size justification for this trial. The planning illustrations should not be treated as an account of the study's enrollment target, a result, or evidence of power achieved by the participants enrolled.

Why can over-dispersion matter in general?

General methods for count outcomes sometimes assume that counts vary according to a particular probability model. Over-dispersion occurs when the observed variation is greater than that model expects. If it is ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. This is a general statistical consideration, not a reported feature of this study. The registry does not post an analysis model for its count or time-to-event secondary outcomes, so it is not possible to say whether over-dispersion was assessed or relevant.

For this record, the central methodological constraint is not a choice among competing statistical tests but the absence of posted analyses. The registry identifies outcomes and a design, but does not report estimates, uncertainty intervals, model specifications, or participant-level analysis details. Any account of the statistical results would require information not reported in the registry record.

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("CCX140-B")
n      <- c(5)
events <- c(2)
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  CCX140-B  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, and reports 14 outcome measures overall. The named secondary outcomes address remission, UPCR change, eGFR change, and time to rescue therapy. Testing or interpreting many outcomes can raise multiplicity concerns in general: the more findings considered, the greater the chance that an apparently notable result may arise by chance when formal testing is used. A prespecified hierarchy or adjustment method can help define how multiple questions are handled.

A hierarchy of hypotheses, a multiplicity adjustment, and the planned order of secondary analyses are not reported in the registry record. Since the record lists 0 analyses, there are no posted p-values or outcome estimates whose multiplicity-adjusted interpretation can be evaluated. The outcome list alone does not show that every outcome was tested or that any particular statistical procedure was used.

The registry record also does not report a missing-data approach, the number assessed for each outcome, or the analysis population used. It does not state how missing week 12 measurements, early discontinuations, or incomplete follow-up were handled. Those omissions are important for a participant-count endpoint because the count needs a clearly defined denominator. The enrollment of 5 participants is not enough to establish how many contributed data to each outcome.

For the same reason, the record does not establish whether outcomes were analyzed according to an intention-to-treat, per-protocol, or other population definition. Those analysis populations are general methodological choices; none is identified in the posted information. The absent details prevent assessment of how missingness or participant exclusions might affect the results. They do not, by themselves, show that data were missing or participants were excluded.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the CCX140-B group: 5 participants were at risk, 0 were affected, and 0 deaths were reported. In the separate other-adverse-event category, 5 participants were at risk and 4 were affected. These are counts in this study, not comparative estimates against a control group.

The serious-adverse-event count should be read as a summary of the events recorded in the registry, not as proof that serious events cannot occur. The number of participants is small, and the record does not provide a comparator group or a detailed account of observation time. It also does not list serious adverse-event terms. The absence of listed serious terms is not a description of which specific events were monitored or how they were defined.

The separate other-adverse-event figure does not identify the event terms, their severity, timing, or whether an individual participant had more than one event. The registry record does not provide those details. These safety counts describe what was posted for the study and cannot establish a comparative safety profile or predict outcomes beyond the participants recorded.

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

The registry entry establishes that a small, open-label, sequential dose-escalation study of CCX140-B was conducted in participants with primary FSGS and nephrotic syndrome. It specifies the initial dose and planned stepwise escalation, identifies a primary UPCR response threshold, and lists additional outcomes related to remission, kidney-function measures, and rescue therapy. It also reports enrollment of 5 participants and a terminated status.

It does not establish how many participants met the primary endpoint. The registry lists 0 analyses and does not post primary or secondary outcome estimates, confidence intervals, or p-values. Accordingly, the posted record cannot show the magnitude, direction, or precision of change in UPCR or the frequency of remission. The endpoint definition should not be mistaken for an endpoint result.

Even if participant-level changes were reported, the design would remain non-comparative. Without a separate control group, changes observed during treatment could not be attributed to CCX140-B with the same strength as a randomized comparison. That limitation concerns what the design can establish; it does not determine whether participants changed or what caused any change.

The safety information records 0 serious adverse events among 5 participants at risk and 4 participants affected in the separate other-adverse-event category. These counts are descriptive and do not provide a controlled comparison or a complete account of event types and timing. They should not be generalized beyond the recorded study participants.

The record also does not state why the study was terminated or provide details about completion, missing measurements, analysis populations, or the statistical plan. Those gaps limit interpretation of both outcome and safety findings. The most defensible reading is therefore about the study's design and the information the registry does and does not report, rather than a conclusion about the treatment's effects.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is expressed as a participant-level threshold response, while its design is an open-label, sequential dose escalation without a separate comparator. That combination makes it important to distinguish a descriptive response count from a comparative estimate. A count can summarize the participants who met the endpoint, but it cannot on its own establish what would have happened under another treatment or without the study medication.

The small enrollment also makes clear reporting of denominators and uncertainty particularly important. For a count endpoint, the number assessed is necessary context for the number meeting the threshold. Confidence intervals can show how imprecise a response estimate may be, but the registry record posts neither the endpoint count nor an interval. With only 5 participants enrolled, each participant's information is central to the description of the study, yet the posted results do not show those outcomes.

The record further illustrates why outcome definitions and outcome results must be separated. It names UPCR reduction, remission, eGFR changes, and rescue therapy as outcomes, but provides no analyses. A registry's list of planned or tracked measures is not a finding. Clear reporting of the estimates, assessed populations, missing-data handling, and analysis methods would be needed to judge how the results answer those questions.

Finally, planning calculations need to match the design and the assumptions under which they are used. The stated planning illustrations assume equal allocation between two arms, whereas this study has no separate comparator group. Recognizing that mismatch helps prevent a planning exercise from being mistaken for evidence about the study's actual results or statistical precision.

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.

Several limitations are specific to the information and design of this study. It is open label and has no separately listed comparator arm, so any within-study change would be descriptive rather than a randomized contrast. The sequential, intra-subject dose-escalation design also means the registry does not provide a parallel group for separating treatment-period changes from changes over time or other influences.

Enrollment was 5 participants. The registry record does not report the number who completed each dose step, reached the week 12 assessment, or contributed data to each secondary outcome. It also does not report the primary endpoint count or the results for the secondary endpoints. This prevents assessment of outcome frequency, variability, and precision.

The status is listed as terminated, but the reason for termination is not reported in the registry record. The record does not specify whether termination affected planned enrollment, dose escalation, or follow-up. Those details should not be inferred from the status alone.

The registry does not report the sample-size justification, a statistical analysis plan, analysis populations, missing-data methods, or a multiplicity strategy. Nor does it provide detailed definitions for the remission outcomes in the posted descriptions. These omissions constrain interpretation, especially because multiple outcomes are listed and no analyses are posted.

The safety summaries are also limited: serious-event terms and details for the separate other-adverse-event category are not reported. The small enrollment and lack of a comparator further limit any broader safety interpretation. These limitations describe what the registry record cannot establish; they do not indicate that a particular adverse event, missing-data pattern, or protocol deviation occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome — NCT03703908.
• Registry record last updated 2025-03-17; status last verified 2025-02.
• Results first posted 2024-02-06.
• 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

NCT03703908 is a phase 2, open-label, sequential intra-subject dose-escalation study of CCX140-B in participants with primary FSGS and nephrotic syndrome. The registry reports enrollment of 5 participants, a start date of 2018-10-01, a primary completion date of 2020-06-24, and terminated status. Participants initially received 5 mg twice daily, with stepwise escalation up to 15 mg twice daily.

The primary endpoint is the count of participants with a UPCR reduction of at least 20% from baseline to week 12. The record lists 14 outcome measures and 0 analyses; it does not post the primary endpoint result or secondary outcome estimates. It reports 0 serious adverse events among 5 participants at risk, 4 participants affected in the separate other-adverse-event category, and 0 deaths. The reason for termination, analysis methods, and missing-data approach are not reported in the registry record.