Belatacept Post Depletional Repopulation to Facilitate Tolerance: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Belatacept Post Depletional Repopulation to Facilitate Tolerance (NCT00565773), a na phase 2 study. The primary outcome is Number of Patients Successfully Withdrawn From Oral Immunosuppression.

2. Clinical Question

3. Trial Design

This is a completed Phase 2 study with a single-group model and no masking. The registry lists an enrollment of 40. Allocation is recorded as not applicable, consistent with the absence of a randomized, parallel-group comparison. The study is described as single center in its brief summary. Its stated focus was an experimental immunosuppressive regimen in renal allograft recipients, including whether participants might later attempt to stop oral sirolimus while continuing belatacept.

The intervention description names alemtuzumab, belatacept, and sirolimus. The arm description states that alemtuzumab was given as a single dose on the day of transplantation and that belatacept and sirolimus were given for 1 year. The brief summary says that, among the initial 20 participants, half tested whether infusion of bone marrow from the kidney donor would improve the effect of the drugs. This detail does not turn the study into a randomized comparison: the registry records a single-group model and does not provide a like-for-like control arm.

The registry dates the study start to 2007-12 and primary completion to 2017-07-01, with status recorded as completed. It lists Organ Transplantation as the condition. The primary endpoint is measured at Year 2 and applies to a selected subgroup: participants who met criteria to wean from sirolimus and opted to try. How the investigators handled the full enrolled group in the primary analysis, including those who were not eligible or did not choose to attempt withdrawal, is not reported in the registry record.

The registry record does not report a detailed statistical analysis plan, an allocation procedure, or a masking procedure beyond the designation of no masking. The study therefore describes experience under the regimen, but its design does not provide a randomized estimate of comparative efficacy.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis includes participants meeting criteria to wean from sirolimus who also opted to attempt sirolimus weaning.

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 Number of Patients Successfully Withdrawn From Oral Immunosuppression, measured over Year 2.

The primary endpoint is the number of participants successfully withdrawn from oral immunosuppression, specified as sirolimus, for one year after their last dose. The registry describes a process in which participants took sirolimus for 1 year and, if they met prespecified criteria, were offered the opportunity to taper it and continue on belatacept monotherapy. Eligibility required a kidney biopsy negative for all signs of rejection, including borderline findings. The endpoint population includes only participants who met the criteria and opted to attempt withdrawal.

A count endpoint expresses how many people in the defined endpoint population met the stated outcome. It is directly interpretable as a tally, but by itself it does not describe the probability of success in the broader transplant population or establish what would have happened under another treatment regimen. The denominator is important for interpreting a count; the registry record does not report the number who met the eligibility criteria and chose to attempt withdrawal, nor does it report the numerical primary endpoint result.

This endpoint addresses whether participants could remain off sirolimus after a planned withdrawal attempt, rather than measuring rejection alone or comparing treatment strategies. The criterion for attempting withdrawal makes the endpoint conditional on eligibility and choice. The registry record does not report further operational detail about how a successful withdrawal was adjudicated beyond the one-year period off sirolimus.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A count endpoint records how many participants satisfy a defined outcome. For the primary endpoint, the outcome is successful withdrawal from sirolimus for one year after the last dose. Counts are straightforward to understand, but a count has meaning only alongside the population and denominator to which it applies. Here the endpoint population is restricted to people who met the stated criteria for weaning and chose to attempt it. The number in that population and the resulting endpoint count are not reported in the registry record.

In general, a confidence interval describes a range of values reasonably compatible with the data under a statistical model. For a count or proportion, an interval can communicate uncertainty that a single point estimate cannot. No confidence interval for the primary endpoint is reported in the registry record. A reader should not infer precision from the fact that the registry gives an enrollment figure: the primary analysis population is narrower, and its size is not stated.

The distinction between a descriptive result and a treatment comparison is important. In a single-group study, an observed outcome describes what happened among participants receiving the studied regimen, subject to the endpoint definition and follow-up. A randomized, concurrent comparison can help distinguish differences associated with treatment assignment from other differences between groups. This study is recorded as single group, with allocation not applicable, so it does not provide that kind of randomized contrast. The brief summary’s reference to standard treatment describes the rationale for the study rather than a comparator arm.

The intervention description combines drugs and a withdrawal strategy. According to the arm description, alemtuzumab was given once on the day of transplantation, while belatacept and sirolimus were given for 1 year. The primary outcome then concerns a selected subset offered withdrawal and continuing belatacept monotherapy. A result on this endpoint would therefore characterize the withdrawal experience among eligible participants who chose to try it, not simply the initial regimen in every enrolled participant.

The primary endpoint is a participant count rather than a continuous measurement such as estimated glomerular filtration rate. A count does not summarize the magnitude of a continuous change, and it does not show the timing of an event unless timing is part of the outcome definition. The registry lists estimated glomerular filtration rate among secondary outcomes, but numerical results for that outcome are not reported in the registry record. The same applies to the listed secondary outcomes concerning rejection, chronic allograft nephropathy, BK viremia, donor-specific alloantibody, and surviving grafts.

The registry lists seven outcome measures and zero analysis records. That listing alone does not explain which analyses were planned, how repeated or related outcomes were handled, or whether any analyses were prespecified outside the registry entry. Those details are not reported in the registry record. General statistical practice would distinguish the primary endpoint from secondary or exploratory outcomes and would describe the analysis population, missing-data handling, and multiplicity approach before interpreting inferential results. The record does not supply those details, so no particular method should be attributed to the investigators.

Multiplicity arises when multiple outcomes or multiple statistical tests are considered. In general, the more inferences made, the greater the chance that at least one result may appear noteworthy by chance if each test is interpreted in isolation. A prespecified strategy can address this issue, for example by identifying a primary outcome and clarifying how secondary outcomes will be interpreted. The registry lists several secondary outcomes but does not report a multiplicity adjustment or a hierarchical testing plan. This lack of reporting does not show that no such plan existed; it means the plan is not reported in the registry record.

Over-dispersion is a general concern when count variation exceeds what a simple statistical model assumes. It can make standard errors too small if the model underestimates variability. The primary endpoint is a participant count, but the registry does not report a model-based analysis or enough outcome information to assess whether over-dispersion is relevant to an actual fitted model. No model should be inferred from the endpoint type alone.

The sample-size assumptions describe planning illustrations using two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with a target effect defined as a fraction of the observed effect. Such calculations are general planning exercises, not observed power, and their assumptions do not describe the registry’s single-group study design. The registry record does not report the numerical observed effect used for these illustrations or any corresponding planning sample sizes. Nor does it report the trial’s own sample-size justification. The enrollment entry of 40 should not be read as evidence of a particular power or as proof that the study was sized to detect a specified effect.

In general, an analysis should also make clear how participants with incomplete follow-up or missing outcome data were handled. The registry record does not report missing-data methods for the primary endpoint. It also does not state whether all enrolled participants were included in an intention-to-treat analysis, whether analyses were restricted to participants who attempted withdrawal, or how outcomes among those not eligible or not willing to attempt withdrawal were treated. The explicitly described primary population is the eligible subgroup that opted to attempt weaning; further analysis-population details are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary sirolimus-withdrawal count and secondary outcomes covering rejection, chronic allograft nephropathy, BK viremia, donor-specific alloantibody, surviving grafts, and estimated glomerular filtration rate. It records zero analysis records. These entries do not describe how the investigators planned to interpret multiple outcomes, whether any adjustment for multiple testing was used, or whether an outcome hierarchy was specified. Those methods are not reported in the registry record.

In general, multiplicity matters because testing multiple outcomes can increase the chance of at least one apparently notable finding if each is treated as an independent opportunity for discovery. The primary endpoint is identified, which helps distinguish the main question from secondary questions, but the record does not state how secondary outcome analyses were intended to affect conclusions. No multiplicity adjustment should be assumed.

The record does not report missing-data methods, the extent of missing outcome information, or a general analysis population. For the primary endpoint, it defines the population as participants who met criteria to wean from sirolimus and opted to attempt weaning. It does not state how participants who were ineligible, declined an attempt, or had incomplete follow-up were handled analytically. The number entering this endpoint population is also not reported.

There is no basis in the registry record for attributing an intention-to-treat, per-protocol, or other named analysis strategy to the investigators. The named endpoint population should be kept distinct from the registry’s overall enrollment entry, and conclusions should remain limited to the information reported.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports safety counts for the immunosuppressive medication combination. For serious adverse events, 40 participants were listed as at risk and 0 as affected. For other adverse events, 40 were listed as at risk and 14 as affected. The record lists 0 deaths, and no top serious adverse event terms are reported.

These are descriptive registry counts, not comparative estimates. The study has no concurrent control group, so the figures do not show how the counts compare with another treatment regimen. The registry record does not provide event-level details, severity breakdowns, timing, follow-up completeness, or definitions beyond the distinction between serious and other adverse events. It is therefore not possible to use these counts alone to assess particular risks or establish that an event could not have occurred. The figures describe what the registry records for the stated groups at risk and should be interpreted within that reporting scope.

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

The registry record describes a completed Phase 2, single-group study of an immunosuppressive regimen in renal allograft recipients. Its primary question concerns the number of eligible participants who chose to attempt sirolimus withdrawal and remained off sirolimus for one year after their last dose. The record does not report the numerical primary endpoint result or the size of the subgroup that attempted withdrawal. It therefore does not support a conclusion about the frequency of successful withdrawal from the posted primary outcome information.

The study’s design also limits what can be concluded comparatively. A single-group study can describe outcomes observed under the regimen, but it does not provide a randomized comparison with standard treatment or another concurrent regimen. The brief summary’s mention of standard treatment is not evidence that a control arm was enrolled. Differences between observed experience and an external expectation could reflect factors other than the treatment strategy.

The registry’s safety entries report 0 participants affected by serious adverse events among 40 at risk, 14 affected by other adverse events among 40 at risk, and 0 deaths. These counts are not a substitute for a comparative safety analysis, and the registry record does not provide detailed event terms for serious events. They should not be interpreted beyond the categories and counts recorded.

More broadly, the registry record does not provide reported inferential analyses, confidence intervals, missing-data methods, or a multiplicity plan. Without the primary result and its denominator, precision cannot be assessed. The study’s findings should not be extended automatically to all renal transplant recipients, because the primary endpoint applies to a selected subgroup meeting biopsy criteria and opting to try withdrawal. The record supports describing the study question and design, but not asserting that the regimen succeeds, fails, or performs better than an alternative.

13. Why This Trial Matters Statistically

This study raises a statistical question that is more specific than whether a medication combination was administered: among recipients who met criteria and chose to attempt it, how many could remain off sirolimus for one year while continuing belatacept monotherapy? Making the endpoint population explicit is important because it differs from the overall enrollment population. A result for the eligible, willing subgroup would not automatically answer the same question for all participants or all transplant recipients.

The record also illustrates the distinction between a treatment strategy and a treatment comparison. The study is recorded as single group, while its brief summary frames the regimen against current standard treatment. Without a concurrent control arm, the design cannot estimate a randomized difference between those approaches. This distinction matters when interpreting studies that address clinically important goals but do not include a direct comparator.

Another statistical issue is that a count requires a clear denominator and transparent handling of participants who do not enter the endpoint population. The registry states the eligibility and choice conditions but does not report the subgroup size or the primary count. That limits both interpretation and assessment of precision. The listed secondary outcomes add further questions, while the record does not describe how multiple outcomes were to be analyzed or interpreted.

Finally, the planning assumptions use a two-arm framework, while the registered trial model is single group. Such planning illustrations are not a description of the trial design and cannot be treated as observed power. Keeping design, outcome definition, analysis population, and planning calculations separate is essential for reading the record accurately.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation in interpreting the registry record is that it does not report a numerical primary endpoint result. It also does not state how many participants met the criteria to attempt sirolimus withdrawal or how many chose to try. Because the endpoint is defined only for that subgroup, the overall enrollment entry does not supply the missing denominator.

The study is single group, with allocation recorded as not applicable and no masking. It therefore does not provide a randomized, concurrent comparison with standard treatment, despite the brief summary’s description of that comparison as a motivation. The brief summary mentions a donor bone marrow infusion among some participants early in enrollment, but the available description is incomplete. The record does not provide enough detail to interpret that component as a separate comparison.

The registry lists seven outcome measures but no analysis records. It does not report statistical methods, confidence intervals, multiplicity handling, missing-data procedures, the primary analysis population beyond its eligibility-and-choice definition, or the trial’s sample-size justification. The sample-size planning assumptions are not the study’s registered single-group design and are not observed power. These omissions limit assessment of precision, robustness, and the planned role of secondary outcomes.

The safety record gives aggregate counts but no serious adverse event terms, event-level descriptions, or comparative safety data. The registry status is completed, but completion alone does not fill in absent outcome or analysis details. These limitations are specific to the information recorded and should not be taken as evidence that unreported methods or results did not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Belatacept Post Depletional Repopulation to Facilitate Tolerance — NCT00565773.
• Registry record last updated 2020-02-11; status last verified 2020-01.
• Results first posted 2020-01-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes NCT00565773, titled Belatacept Post Depletional Repopulation to Facilitate Tolerance, as a completed Phase 2, single-group study in renal allograft recipients. The recorded enrollment is 40, masking is none, and allocation is not applicable. The intervention description includes alemtuzumab, belatacept, and sirolimus; the arm description specifies a single alemtuzumab dose on the day of transplantation and belatacept and sirolimus for 1 year.

The primary endpoint is the number of participants successfully withdrawn from sirolimus for one year after their last dose, among those who met weaning criteria and chose to attempt it. The numerical primary result and the size of that endpoint population are not reported in the registry record. Safety counts list 0 serious adverse event cases among 40 at risk, 14 other adverse event cases among 40 at risk, and 0 deaths. The record lists seven outcome measures and no analysis records.