A Study of Belimumab in the Prevention of Kidney Transplant Rejection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Belimumab in the Prevention of Kidney Transplant Rejection (NCT01536379), a randomized phase 2 study. The primary outcome is Change From Baseline in naïve B Cells From Baseline to Week 24.

2. Clinical Question

3. Trial Design

The record describes a completed Phase 2 pilot study with randomized allocation, double masking, and a parallel-group design. It enrolled 30 participants and compared belimumab plus standard of care with placebo plus standard of care after kidney transplantation. Both groups received standard transplant care, so the planned contrast concerns adding belimumab rather than replacing usual care.

The belimumab arm is described as receiving 10 mg/kg by infusion on Days 0, 14, and 28, then every 4 weeks thereafter, for a total of 7 infusions. The last dose was scheduled for the Week 20 visit. The placebo arm followed the corresponding infusion schedule. The study summary describes follow-up assessments at 24, 36, and 52 weeks after surgery, including blood testing for immune-system effects. The primary endpoint timeframe was baseline and Week 24.

The primary analysis population was the Modified Intent to Treat population. Its registry definition includes randomized participants who received at least one dose; for the naïve B-cell analysis, participants also needed Week 24 data. The posted primary endpoint arm counts were 9 for placebo and 7 for belimumab. These are the endpoint analysis counts, not a replacement for the overall enrollment figure.

The registry record does not report the sample-size justification, planned allocation ratio, or a detailed protocol-level statistical analysis plan. It also does not report interim analyses. These omissions limit what can be concluded about the study’s original design assumptions or any planned decision rules.

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: Participants were randomized to 1 of the 2 treatments groups in a 1:1 ratio and received standard of care in addition to investigational products (IPs). Participants received IP infusion on Day 0, Day 14, Day 28 and every 4 weeks thereafter for a total of 7 infusions.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent to treat (MITT) Population

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 Change From Baseline in naïve B Cells From Baseline to Week 24, measured over Baseline and Week 24.

The primary endpoint was change from baseline in naïve B cells from baseline to Week 24, measured in cells/mm^3. The registry defines a naïve B cell as a cell not exposed to antigen and describes the count as the concentration of CD20+CD27 cells. Change was defined as the Week 24 value minus the baseline value, with baseline taken on Day 0, the day of transplant.

This is a continuous immune-cell measure. In general, such an endpoint describes the magnitude and direction of change in a measured biological quantity. It can help characterize whether the study treatment is associated with a difference in that quantity over the stated period. It does not, by itself, establish a difference in kidney rejection or another clinical outcome.

The registry reports least-squares means and standard errors for the arm-level results, and describes an adjusted treatment-placebo difference estimated using a repeated-measures model. The analysis population included participants with Week 24 naïve B-cell data. That means the reported primary result pertains to this defined immune-cell endpoint and analysis population, not necessarily to every enrolled participant or to all outcomes relevant after transplantation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint was analyzed as a continuous outcome: change in naïve B-cell count between baseline and Week 24. The registry reports least-squares means, standard errors, and a treatment-placebo difference with a 95% confidence interval. It describes a mixed-model repeated-measures analysis, rather than a simple comparison of only the two posted arm summaries.

What does a least-squares mean represent?

In general, a least-squares mean is a model-based estimate of an arm’s mean after accounting for specified terms in the model. It is not necessarily identical to the raw arithmetic average. Here, the registry says the model included treatment, visit, donor type, and treatment-by-visit interaction as fixed categorical effects. It also included baseline and baseline-by-visit interaction as fixed continuous covariates. These terms describe how the model adjusted the estimated means and treatment contrast.

Why use repeated-measures modeling?

In general, repeated-measures models are used when measurements are collected across visits for participants. They can estimate treatment patterns over time while accounting for the fact that observations from the same participant may be related. The registry identifies a compound symmetry variance structure for within-participant errors, shared across treatments. In general, a variance structure specifies how the model represents the relationship among repeated observations; compound symmetry uses a common pattern for those relationships. The record does not provide further diagnostics or a rationale for selecting that structure.

The registry’s description includes a treatment-by-visit interaction. In general, that interaction allows the treatment contrast to vary across visits rather than forcing one common contrast at every visit. Baseline and baseline-by-visit terms allow baseline values to be related to the outcome and to do so differently across visits. Donor type is another adjustment term. These model details are relevant because the reported difference is adjusted, not simply a subtraction of unadjusted arm averages.

How should the standard errors and confidence interval be read?

In general, a standard error summarizes the uncertainty in an estimated mean; it is not the standard deviation of individual participants’ measurements. The reported standard errors are 25.55 for placebo and 27.5 for belimumab. A confidence interval expresses a range of estimates compatible with the data and model under the procedure used. The reported 95% interval for the treatment-placebo difference runs from -109.5 to 40.7. Because it includes both negative and positive values, it does not provide a precise direction for the difference. The registry does not report a p-value for this result.

The arm-level changes are 4.0 for placebo and -30.4 for belimumab, while the reported difference is -34.4. The registry describes the difference as adjusted and derived from the repeated-measures model. It should therefore be interpreted as the model’s treatment-placebo estimate, not as an independently verified recalculation from the arm-level summaries.

What does the analysis population mean?

The Modified Intent to Treat population included randomized participants who received at least one study dose. For this endpoint, the registry says participants analyzed were those with Week 24 naïve B-cell data. This defines who contributed to the reported endpoint analysis. The record does not describe a separate imputation procedure or give enough detail to establish how all missing repeated measurements were handled. In general, model-based analyses can use available repeated observations under assumptions about missingness, but those assumptions and their assessment are not reported.

The posted endpoint counts are 9 for placebo and 7 for belimumab, whereas overall enrollment was 30. The distinction matters: enrollment describes the study as a whole, while the smaller arm counts identify participants with data included in this endpoint analysis. The registry does not explain the reasons each participant lacked endpoint data.

What can a planning illustration tell a reader?

In general, a sample-size planning illustration asks how many participants might be required under stated assumptions to detect a chosen effect with a chosen error rate. Such an illustration is not an observed result and is not observed power. The registry record does not report the trial’s own sample-size justification. The posted results also indicate that values were missing or not estimable for a two-arm comparison of this continuous endpoint, so no specific planning count can be interpreted from that basis.

Overall, the model description makes clear that the reported treatment contrast was adjusted for prespecified covariates and repeated measurements. It does not remove uncertainty from the small endpoint analysis group, nor does it supply unreported details about model checks, missing-data assumptions, or the handling of multiple outcomes.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo", "Belimumab 10mg/kg")
n   <- c(9, 7)
m   <- c(4, -30.4)
sp  <- c(25.55, 27.5)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo  9  4.000  76.650  -54.918  62.918
CARM  Belimumab 10mg/kg  7  -30.400  72.758  -97.690  36.890

11. Analyses Reported by the Sponsor

The registry reports the study’s own treatment-placebo mean difference as -34.4, with a 95% confidence interval from -109.5 to 40.7. The primary endpoint description attributes adjusted mean differences and confidence intervals to a mixed-model repeated-measures analysis. This model-based result is the relevant sponsor analysis for interpreting the registry’s primary endpoint.

The reported arm-level changes are 4.0 for placebo and -30.4 for belimumab, with standard errors of 25.55 and 27.5. A simple unadjusted calculation from arm summaries would not reproduce all features of the registry’s adjusted repeated-measures analysis, which accounts for the listed model terms. The registry record does not provide a separate recalculated treatment contrast for this endpoint; it notes that values were missing or not estimable for a two-arm comparison of the continuous endpoint.

The confidence interval spans negative and positive values, and the registry does not report a p-value. The appropriate reading is therefore an uncertain model-based estimate, not a definitive separation between treatment groups. The record does not flag a discrepancy between an independent recalculation and the sponsor’s result.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 35 outcome measures, 28 analyses, and 14 posted secondary outcomes. The primary endpoint was change in naïve B-cell count through Week 24. The secondary outcomes include immune-cell counts and percentages at Week 24 and Week 52, such as memory B-cell, activated memory B-cell, transitional B-cell, activated T-cell, and regulatory T-cell measures. These outcomes span several cell types and time points.

When many outcomes are examined, the chance of finding an apparently notable result by chance can increase. In general, multiplicity procedures may adjust interpretation or testing across a family of outcomes. The registry record does not report whether a multiplicity adjustment was planned or used, how outcome families were defined, or which secondary analyses were considered confirmatory. Accordingly, the secondary results should not be treated as equivalent to a single prespecified primary comparison unless the registry record establishes that status.

The record identifies the Modified Intent to Treat population for the primary endpoint and specifies that participants needed Week 24 data for the naïve B-cell count analysis. It does not report a complete account of missing observations, reasons for missingness, or a separate imputation method. The repeated-measures model is described, but the assumptions about missing data and any sensitivity analyses are not reported in the registry record.

The sample-size justification is also not reported. The record therefore does not establish whether enrollment was based on a formal power calculation, a feasibility target, or another rationale. It likewise does not report interim analyses. These omissions make it difficult to assess the intended inferential status of the many outcomes or the assumptions underlying the planned study size. They do not alter the posted estimates, but they constrain how broadly those estimates can be interpreted.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: blood creatinine increased (8.3%), clostridium difficile colitis (8.3%), colitis (8.3%), dehydration (8.3%), delirium (8.3%).

The registry reports serious adverse events for 7 of 13 participants at risk in the placebo group and 5 of 12 at risk in the belimumab group. Other adverse events were reported for 9 of 13 participants at risk in the placebo group and 9 of 12 at risk in the belimumab group. These are descriptive participant counts. The record does not provide a statistical comparison of the groups for these figures.

The serious-event terms listed include blood creatinine increased, Clostridium difficile colitis, colitis, dehydration, delirium, and diarrhoea, each reported as 8.3%. The registry excerpt does not assign those terms to a treatment group in the listed summary, so they should not be interpreted as group-specific counts from that information alone. Death counts are not reported in the registry record.

In general, adverse-event counts describe events observed during the study and are not, by themselves, evidence that the assigned treatment caused an event. The groups were small, and the counts should not be converted into a comparative safety conclusion without a specified analysis and adequate context. These figures are distinct from the primary immune-cell endpoint and do not resolve its uncertainty.

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

The primary result describes a model-based difference in change in naïve B-cell count from baseline to Week 24. The point estimate was -34.4, and its 95% confidence interval ranged from -109.5 to 40.7. Because the interval contains negative and positive values, the estimate is imprecise about the direction and size of the treatment-placebo difference. The registry does not report a p-value for this comparison.

The result does not establish that belimumab prevents kidney transplant rejection. The primary endpoint is a biological cell-count measure, not a rejection event, graft outcome, or patient-centered clinical endpoint. The study’s rationale concerns immune mechanisms after transplantation, but a change in an immune-cell measure cannot be assumed to translate into a clinical outcome.

The endpoint analysis included 9 placebo participants and 7 belimumab participants. The overall enrollment was 30, but the endpoint result applies to participants with the required Week 24 data under the stated analysis definition. The record does not explain all differences between the enrollment and endpoint analysis counts.

Nor does the result establish that there is no treatment difference. The confidence interval allows a range of possible effects in both directions, and the small analysis groups limit precision. The result is best understood as an estimate from a Phase 2 pilot study that can describe the observed endpoint data but cannot settle a broader clinical question on its own.

Safety counts are likewise descriptive. They report participants with serious and other adverse events, but the registry does not provide a comparative statistical analysis for those counts. Neither the efficacy-related endpoint nor the event counts should be interpreted as a clinical recommendation.

15. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a biological endpoint and a clinical outcome. Naïve B-cell count is relevant to the study’s immune-system rationale, but it is not itself a measure of transplant rejection. Keeping that distinction clear prevents a mechanistic measurement from being mistaken for direct evidence about a clinical event.

The study also shows why estimates and their precision need to be read together. The reported treatment-placebo difference is -34.4, but the 95% confidence interval from -109.5 to 40.7 is broad and includes values in both directions. A point estimate alone would conceal that uncertainty. The endpoint analysis groups were small, with 9 placebo participants and 7 belimumab participants contributing to the posted primary result.

The model description is another useful feature for statistical interpretation. The sponsor analysis used a mixed-model repeated-measures approach with treatment, visit, donor type, treatment-by-visit interaction, baseline, and baseline-by-visit interaction. Those details clarify that the reported contrast is adjusted and should not be conflated with a simple comparison of arm summaries.

Finally, the record lists multiple outcomes and analyses. Without a reported multiplicity plan, readers should distinguish the primary endpoint from secondary immune-cell measurements and avoid treating every result as independently confirmatory. The record also leaves important details about sample-size justification and missing-data handling unreported. These limits are part of the statistical context, not reasons to infer results that the record does not state.

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 endpoint analysis included 9 participants in the placebo arm and 7 in the belimumab arm. These counts are small, and the confidence interval for the reported treatment-placebo difference is wide. The resulting estimate is imprecise and may be sensitive to the observations included in the analysis.

The endpoint measures naïve B-cell count rather than kidney rejection or another direct clinical outcome. Although the registry describes a rationale involving immune cells, the primary result alone cannot establish an effect on rejection. The record excerpt also does not provide numerical primary results for clinical rejection outcomes.

The registry describes the repeated-measures model and its covariates, but does not report model diagnostics, the rationale for the compound symmetry structure, or sensitivity analyses. The endpoint population required Week 24 data, and the record does not explain the reasons for missing endpoint data or report a separate imputation strategy. The assumptions underlying any use of incomplete repeated observations are not reported.

The sample-size justification and any interim analyses are not reported in the registry record. Multiplicity handling across the listed outcomes is also not reported. These omissions limit assessment of the planned precision and the inferential status of secondary results. The serious adverse-event terms are listed with percentages but are not assigned to groups in the summary, and deaths are not reported in the registry record. Safety counts therefore provide limited context for comparing the arms.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study of Belimumab in the Prevention of Kidney Transplant Rejection — NCT01536379.
• Registry record last updated 2017-04-25; status last verified 2017-03.
• Results first posted 2017-04-25.
• 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

This completed Phase 2 pilot study randomized adults after kidney transplantation to belimumab 10 mg/kg plus standard of care or placebo plus standard of care. The design was parallel-group and double-blind, and the record reports enrollment of 30 participants.

The primary endpoint was change in naïve B-cell count from baseline to Week 24. The posted analysis included 9 placebo participants and 7 belimumab participants. The reported treatment-placebo difference was -34.4, with a 95% confidence interval from -109.5 to 40.7; no p-value is reported.

The result concerns an immune-cell measure, not transplant rejection. Its uncertainty, small endpoint analysis groups, multiple outcomes, and unreported details about missing-data handling and multiplicity limit the conclusions that can be drawn from the registry record.