Treg Modulation With CD28 and IL-6 Receptor Antagonists: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treg Modulation With CD28 and IL-6 Receptor Antagonists (NCT04066114), a na phase 1, phase 2 study. The primary outcome is The Proportion of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated or Antibody-mediated Rejection (as Defined by Banff Criteria) at 6 Months Post-transplantation..

2. Clinical Question

3. Trial Design

The registry describes a completed Phase 1/Phase 2 study of a biologic regimen in kidney transplantation. It lists enrollment of 24 and a single-group model. Allocation is recorded as not applicable, and masking is recorded as none. These features mean the record does not describe a randomized comparison or a blinded evaluation. The trial began on 2019-12-11, and the primary completion date is 2023-09-14.

The intervention is a combination rather than a single agent: lulizumab pegol is paired with tocilizumab, belatacept, everolimus, antithymocyte globulin (rabbit), steroids, and other listed immunosuppressive drugs. The brief study summary identifies safety as the purpose of evaluating lulizumab pegol with tocilizumab, belatacept, and everolimus. The primary endpoint is a rejection-free proportion at six months after transplantation, while the listed secondary endpoint concerns remaining free of biopsy-proven acute rejection at 12 months.

Because the study is single-group, the main endpoint is naturally described as an outcome proportion in the enrolled study population, not a contrast between treatment groups. The registry record does not report a prespecified statistical analysis plan, a sample-size justification, an interim-analysis plan, or details of how the endpoint estimate was calculated. It also does not report a primary endpoint result, participant-level disposition, or the number included in the six-month endpoint assessment. The overall enrollment figure should not be treated as the endpoint denominator without that information.

The adverse-event record contains two differently titled groups, “Transplanted/Received Lulizumab” and “Enrolled Living Donor.” These are not identified as randomized treatment arms, and the registry explicitly cautions that they are not a like-for-like control comparison. Their adverse-event figures should therefore be read as separate descriptive records, not as evidence of a comparative safety effect.

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: Potential participants signed informed consent and enrolled before undergoing any study procedures. Screening criteria were evaluated to determine study eligibility. Participants were enrolled prior to transplantation. Living donors were asked to consent (at which point they were considered enrolled) for a single blood draw and minimal medical information.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population, which includes the same subjects as the safety population, subset to participants who remained in the study in the 6 months following transplantation.

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: Intent-to-treat population, which includes the same subjects as the safety population

6. Primary Endpoint

The registry lists the primary outcome as The Proportion of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated or Antibody-mediated Rejection (as Defined by Banff Criteria) at 6 Months Post-transplantation., measured over 6 months post-transplantation.

The primary endpoint is the proportion of participants who remain free of biopsy-proven acute T-cell mediated or antibody-mediated rejection at six months post-transplantation. It uses a clinically relevant event definition to classify whether an acute rejection endpoint occurred during the specified period. The registry says acute T-cell mediated rejection was defined using Banff 2007 criteria, with a Banff grade greater than or equal to 1A meeting the endpoint threshold. The listed severity grades run from 1A, the mildest form of cellular rejection, to 3, the most severe.

Antibody-mediated rejection was defined using diffusely positive C4d staining, circulating anti-donor antibodies, and morphologic evidence of acute tissue injury. The endpoint also counted clinical rejection treated before six months when there was no biopsy confirmation. This addition means that the endpoint was not limited to biopsy-confirmed events in every circumstance.

In general, a rejection-free proportion condenses a defined follow-up outcome into a fraction of participants meeting the event-free definition. Its interpretation depends on the endpoint rules, the assessment period, and which participants were assessed. Here the registry specifies the six-month period and eligibility population, but does not report the observed proportion, its confidence interval, or the endpoint denominator. The endpoint definition can therefore be described, but its observed frequency and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group endpoint estimate represent?

In general, a single-group study can describe the frequency of an outcome among participants observed under the study regimen. For a binary endpoint, each participant is classified according to whether the specified event-free or event definition is met during the assessment period, and the resulting proportion describes the observed group. That proportion is not automatically a treatment effect. A treatment effect usually requires a contrast with a defined comparator, and the registry records no randomized comparator for this study.

For this trial, the primary measure is the proportion remaining free of the specified acute rejection endpoint at six months post-transplantation. The event definition combines biopsy-based criteria with clinical rejection treated before six months even without biopsy confirmation. In general, such explicit definitions are important because changing which cases count can change the interpretation of an endpoint. The record does not report how the endpoint classifications were adjudicated or how incomplete assessments were handled.

What does a confidence interval communicate?

In general, a confidence interval expresses sampling uncertainty around an estimate under a particular statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It does not correct for bias, establish causation, or guarantee that the estimate applies beyond the population studied. The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but does not report the interval endpoints, the observed proportion, or the method used to construct the interval. Its precision therefore cannot be evaluated from the record.

A binary proportion is often accompanied by an interval because a point estimate alone can give an incomplete picture of uncertainty. The suitability of a particular interval method can depend on the number of observed outcomes and the denominator. Neither the endpoint count nor the denominator is reported, so no method-specific assessment is possible. No interval should be reconstructed from the enrollment figure alone.

Why does the comparator matter?

In general, a randomized comparison can help separate treatment differences from other differences between groups, while a single-group estimate cannot by itself establish what would have happened under another treatment or without the study regimen. This study is listed as single-group, with no allocation and no masking. Its primary endpoint can therefore be interpreted as a descriptive outcome for the study population if the result is reported, not as a direct estimate of comparative benefit. The adverse-event grouping does not change that design; the registry says the groups are not a like-for-like control comparison.

Even where an external or nonrandomized comparator is available, differences in eligibility, follow-up, or outcome assessment can complicate comparisons. No such comparative analysis is reported for the primary endpoint in this record. A causal contrast should not be inferred from separate group counts or from the regimen’s observed outcomes in isolation.

What is over-dispersion, and is it relevant?

In general, over-dispersion refers to observed variability greater than a statistical model assumes. It can matter when a model’s uncertainty calculations rely on a variance assumption that does not fit the data; uncertainty may then be understated if the extra variability is ignored. Over-dispersion is most directly relevant to certain modeled count or rate outcomes. It is not a fact established by simply having a binary proportion endpoint.

The registry record does not report a model for the primary endpoint, a dispersion assessment, or a statistical analysis plan. It would therefore be inappropriate to claim that over-dispersion was present, absent, tested, or adjusted for in this study. The concept is general context rather than a reported feature of this analysis.

How should planning calculations be understood?

In general, sample-size planning calculations ask how many participants may be needed under specified assumptions to detect a chosen effect with a chosen significance level and power. They are planning illustrations, not observed outcomes and not “observed power.” The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. The record also cautions that these calculations are not the trial’s own design.

Those assumptions do not make this single-group study a randomized two-arm comparison. They describe a planning illustration, not the actual allocation recorded for this trial. The registry does not report a sample-size justification for the trial itself. Since no primary endpoint estimate is reported in the record, the planning illustration should not be treated as evidence about the endpoint’s observed precision or as proof that the study had adequate power. Any displayed planning values should be understood as conditional on their assumptions, not as numbers of participants actually analyzed or as an observed treatment effect.

What can be concluded from the reported analysis details?

The record identifies a primary binary endpoint and a 95% confidence interval as its dispersion measure, but reports 0 analyses. This means there is no analysis result in the registry record to interpret for that endpoint. The record also does not state an adjustment strategy, model specification, handling of missing endpoint observations, or prespecified analysis population beyond its description of the intent-to-treat population. These omissions limit interpretation of the planned statistical approach; they do not establish that no analysis was performed outside 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("Transplanted, Received Lulizumab")
n      <- c(6)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Transplanted, Received Lulizumab  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint at six months and lists a secondary outcome concerning remaining free of biopsy-proven acute T-cell mediated or antibody-mediated rejection at 12 months. It records 2 outcome measures, but does not report a multiplicity strategy. In general, assessing several outcomes can increase the chance of a false-positive finding if each is tested separately. Statistical plans may address that issue through prespecified hierarchies or adjustments, but the registry record does not say whether such methods were planned or used. No claim about control of multiplicity can be made from the available record.

The primary population is described as the intent-to-treat population, the same subjects as the safety population, subset to participants who remained in the study in the six months following transplantation. This wording identifies the intended population description, but the record does not report the number assessed, the number with missing endpoint information, reasons for missingness, or how such observations were treated in the analysis. It also does not report a sensitivity analysis for missing data.

In general, missing outcomes can affect an estimate when participants without observed outcomes differ systematically from those with observed outcomes. The direction and size of that influence depend on why observations are missing and on the analysis method. No missing-data pattern or method is reported, so the extent of any such influence cannot be evaluated. Enrollment of 24 should not be assumed to be the denominator for the six-month result.

The registry record does not report interim analyses, stopping rules, or a statistical analysis plan. Their absence from the record should be read as unreported information, not as evidence that those procedures did or did not occur.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transplant rejection (37.5%), covid-19 (37.5%), urinary tract infection (37.5%), acute kidney injury (37.5%), sepsis (25.0%).

The registry reports adverse-event counts in two groups, but cautions that these are not a like-for-like control comparison. In the “Transplanted/Received Lulizumab” group, 8 participants were listed at risk for serious adverse events and 8 as affected; for other adverse events, 8 were listed at risk and 5 as affected. The record lists 0 deaths. In the “Enrolled Living Donor” group, 9 were listed at risk for serious adverse events and 0 as affected; for other adverse events, 9 were listed at risk and 0 as affected. The record also lists 0 deaths for that group.

The serious-event terms include transplant rejection, COVID-19, urinary tract infection, and acute kidney injury, each listed at 37.5%, as well as sepsis at 25.0% and febrile neutropenia at 12.5%. The registry does not report the denominator or further details needed to interpret those percentages. The percentages should not be converted into event counts or compared across groups based on assumptions. In general, adverse-event summaries describe what was recorded; counts alone do not establish that an intervention caused an event or provide a controlled estimate of comparative safety.

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

The record establishes that a completed Phase 1/Phase 2, single-group study evaluated a regimen including lulizumab pegol and other immunosuppressive agents in kidney transplantation. It specifies a six-month primary endpoint intended to measure freedom from defined acute rejection, and it describes the relevant rejection criteria. It also records adverse-event counts and selected serious-event terms. These details help define what was studied and what kinds of outcomes were recorded.

The registry record does not report the primary endpoint result. It gives no observed rejection-free proportion, confidence interval, or endpoint denominator, and it records 0 analyses. As a result, the primary endpoint’s observed frequency and statistical precision cannot be assessed from this record. The enrollment figure does not substitute for an endpoint result or analysis population count.

The study’s single-group design also limits what its results could establish even if the endpoint estimate were reported. Without a like-for-like comparison, an observed outcome proportion cannot on its own show what would have happened under another regimen or without the regimen. The adverse-event group labels do not create a valid control comparison; the registry explicitly cautions against treating them as like-for-like arms.

In general, statistical uncertainty and design limitations are separate considerations. A confidence interval can describe uncertainty around an estimate, but it cannot remove the limitations of an uncontrolled design. Conversely, a clear endpoint definition does not supply a missing numerical result. The listed adverse-event percentages are descriptive and their denominator is not reported, so they should not be used to infer comparative safety or causation.

Accordingly, the registry supports a description of the study question, design, endpoint rules, and recorded safety information. It does not support a conclusion about the observed six-month rejection-free proportion, a comparative treatment effect, or a causal interpretation of the adverse-event figures.

14. Why This Trial Matters Statistically

This trial illustrates why study design and outcome reporting must be considered together. A clearly defined primary endpoint can make the intended outcome understandable, but interpretation still requires the actual estimate, its denominator, and a measure of uncertainty. The registry describes all three key elements of the endpoint definition and names a 95% confidence interval, yet does not report the result or interval. Without those values, readers cannot judge the observed frequency or its precision.

The single-group design is also central to the statistical question. A proportion can summarize what happened in the study population, but it does not provide a treatment contrast by itself. This distinction is important when a study’s purpose includes safety evaluation and when adverse-event summaries appear in more than one group. Group labels and separate counts do not establish comparability, and the registry specifically warns that the groups are not a like-for-like control comparison.

The record further demonstrates that outcome definitions can combine different sources of evidence. Biopsy-defined criteria are specified for rejection, while clinical rejection treated without biopsy confirmation before six months is also included. That rule has direct implications for what the endpoint represents and should accompany any interpretation of an eventual estimate.

Finally, reporting of analysis methods, missing-data handling, multiplicity, and endpoint denominators is necessary to assess how an estimate was produced and how robust it may be. These details are not reported in the registry record. The resulting statistical lesson is not a judgment about the regimen, but a reminder that a trial’s question, design, outcome definition, and numerical analysis answer different parts of the evidence problem.

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 trial-specific limitations constrain interpretation of the registry record. First, the study is listed as single-group, with allocation not applicable and masking none. There is no randomized, like-for-like control comparison for the primary endpoint. The registry’s “Enrolled Living Donor” group is not identified as a comparator arm and is explicitly not a like-for-like control.

Second, although the primary endpoint is defined in detail, its result is not reported. The record gives no six-month rejection-free proportion, confidence interval endpoints, or analysis denominator. Enrollment of 24 cannot be assumed to equal the number assessed at six months, especially because the endpoint population is described as participants who remained in the study during that period. The record does not report disposition or missing endpoint data.

Third, key analysis details are unreported: the statistical analysis plan, the method for calculating the confidence interval, handling of incomplete observations, multiplicity procedures, and any interim-analysis plan. The registry records 0 analyses, so the endpoint’s reported statistical analysis cannot be examined.

Fourth, adverse-event percentages are listed without a stated denominator or additional context. The group counts are descriptive and do not support a causal or comparative safety conclusion. The study evaluates a multi-agent regimen, so the registry record does not isolate the contribution of any one listed agent.

These limitations describe what cannot be established from the registry record; they do not show that the relevant analyses or procedures were absent elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treg Modulation With CD28 and IL-6 Receptor Antagonists — NCT04066114.
• Registry record last updated 2026-09-24; status last verified 2026-09.
• Results first posted 2024-10-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed Phase 1/Phase 2, single-group study of a kidney-transplant regimen including lulizumab pegol, tocilizumab, belatacept, and everolimus, along with other listed immunosuppressive agents. Enrollment is 24. The primary endpoint is the proportion remaining free of defined acute rejection at six months post-transplantation, with a 95% confidence interval specified as the dispersion measure.

The record describes Banff-based rejection criteria and includes treated clinical rejection without biopsy confirmation in the endpoint definition. It also lists a 12-month rejection-free secondary outcome. The primary endpoint’s estimate, confidence interval, and denominator are not reported, and the record lists 0 analyses. Adverse-event figures are reported for two groups, which the registry says are not a like-for-like control comparison. Statistical analysis details, missing-data handling, and multiplicity procedures are not reported in the registry record.