A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation (NCT00455013), a randomized phase 2 study. The primary outcome is Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, multicenter, parallel-group Phase II study. Participants were assigned to one of three regimens: belatacept with MMF, belatacept with sirolimus, or tacrolimus with MMF. The registry lists an enrollment of 93. The study status is completed; the recorded start was 2007-07 and the primary completion was 2008-10. The registry does not report the number assigned to each group in the information.

Each regimen included thymoglobulin. The belatacept descriptions specify intravenous dosing that began with 10 mg/kg on Days 1 and 5, continued every other week through Month 3, then every 4 weeks through Month 6, and after 6 months used 5 mg/kg every 4 weeks until 12 months. The MMF regimen is listed as 1g twice daily. The sirolimus description gives 5 mg/day on Day 1 of transplantation, but its subsequent dosing details are not reported in the registry record. For the comparator, oral tacrolimus is listed as 0.1 mg/kg/day in divided doses, with an initial target trough level of 8-12 ng/mL for Days 1 - 30 and a later 12 hour trough target of 5-10 ng/mL for 12 months; the regimen also included MMF 1g twice daily.

The primary outcome was assessed from Day 1 to Month 6 after transplantation. Secondary outcomes covered acute rejection through Month 12, graft loss or death, composites involving death, graft loss and acute rejection, delayed graft function, new onset diabetes mellitus, use of anti-hypertension medications, and blood pressure. The registry lists 20 outcome measures but no analysis records. The detailed protocol, allocation procedure, and justification for the enrollment target are not reported in the registry record.

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: Epstein-Barr virus positive recipients of renal allograft from living or deceased donor. Excluded if panel reactive antibodies greater than, equal to (\>=) 50 % or prior graft loss due to acute rejection. 93 participants randomized; 89 transplanted/treated: (1) fever on the day of surgery, (1) problem with allograft, and (2) withdrawal of consent.

Short Term Period

Reasons for not completing this period:

Long Term Extension (LTE)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants with more than one episode of AR were counted once only and the episode with the worst grade was used. For 95% Confidence Interval (CI) within each group, normal approximation was used if N greater than, or equal to (\>=) 5. Otherwise, exact method was used. ITT population defined as all randomized and transplanted participants.

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: All participants who received transplant and were treated with drug were analyzed up to Month 12 post transplant.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population, measured over Day 1 to Month 6 post-transplantation.

The primary endpoint was the number of participants with acute rejection of the transplant from Day 1 through Month 6, in the intent-to-treat population. It counted participants, not episodes: a participant with more than one episode was counted once, and the episode with the worst grade was used.

The registry defines acute rejection as a clinicopathological event requiring clinical evidence and biopsy confirmation by a central pathologist. The described criteria include a renal biopsy showing histologic evidence of rejection and an unexplained rise in SCr of at least 25% from baseline, together with one or more clinical features or circumstances listed in the record. These include decreased urine output, fever, graft tenderness, SCr remaining elevated 14 days after transplantation with clinical suspicion of acute rejection, or treatment for an episode for another stated reason.

The record refers to the Banff 97 working classification, including tubulointerstitial rejection, vascular rejection, and severe rejection with arterial changes. This clinical endpoint is used to capture a defined transplant complication within a specified follow-up period. Its interpretation depends on the registry's biopsy and clinical criteria, not on symptoms alone. The numbers of participants meeting the endpoint, group-specific confidence intervals, and any between-group test are not reported in the registry record, so the magnitude and precision of any treatment-group difference cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary at the participant level: each participant either met the acute-rejection definition during the stated period or did not. The outcome is presented as a number of participants with an event, rather than as an average measurement. The registry says that recurrent episodes do not increase the participant count; only one count is recorded per participant, using the episode with the worst grade. This avoids counting one participant repeatedly in the endpoint total, but it does not make the event count a measure of episode frequency or severity across all episodes.

A confidence interval expresses the uncertainty around an estimate under a statistical method. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. A 95% confidence interval is a procedure that, under its assumptions, would cover the underlying quantity in 95% of repeated applications. It is not a statement that a particular treatment effect has a 95% probability of falling in a specific interval. The registry describes how within-group 95% confidence intervals were selected: normal approximation when N was greater than or equal to 5, and an exact method otherwise. The actual intervals are not reported in the registry record.

In general, a normal approximation uses a mathematical distribution to estimate uncertainty and is most reliable when its assumptions are reasonable. An exact method calculates uncertainty using a method suited to discrete event counts, without relying on the same large-sample approximation. For binary outcomes, sparse counts can make approximate methods less dependable, which is why an exact approach may be used for smaller group counts. This is a general explanation of the methods named in the registry, not a claim that a particular method produced a specific result in this trial.

A group-specific interval and a treatment comparison answer different questions. A group-specific interval concerns the event rate in one group. A comparative estimate concerns the difference or another contrast between groups and needs its own uncertainty calculation. Overlap or non-overlap of separate group-specific confidence intervals is not, by itself, a replacement for a formal comparison. The registry information does not report a comparative estimate or test for the primary endpoint, so no statistical evidence for or against a group difference can be inferred from the interval-method description.

The trial is described as randomized and parallel-group. In general, random assignment is intended to make treatment groups comparable in expectation, so a properly conducted comparison can estimate the effect of assignment to the regimens. The registry record does not describe the sequence-generation or concealment procedures, or the planned comparative model. Its open-label status means that treatment assignment was not masked. Whether this could influence a specific outcome depends on how that outcome is measured and managed; the record does not report a bias assessment.

The record labels the primary population as intent to treat, but the accompanying definition is cut off. In general, an intent-to-treat analysis aims to analyze participants according to their randomized assignment, regardless of later treatment changes, subject to the stated population definition and available outcome data. That general description should not be taken as confirmation of the exact handling of participants in this trial. The full population definition, missing-outcome rules, and analysis denominators are not reported in the registry record.

Planning calculations are distinct from observed trial results. A sample-size illustration based on an observed effect is not observed power and does not establish that the study had adequate power for its actual analysis. The registry describes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. It also distinguishes participant counts per arm for outcomes other than time-to-event outcomes, for which the illustration uses a total event count. Numerical planning results are not reported in the registry record. Because the primary outcome results are not reported either, the observed effect underlying any such illustration cannot be assessed from this record.

Finally, the registry lists 20 outcome measures and zero analysis records. A listed outcome is a planned or recorded measure, not necessarily a reported result. The absence of analysis records means the registry information does not document an analysis result for the listed outcomes; it does not establish that no analysis was conducted elsewhere. No multiplicity adjustment or complete statistical analysis plan is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including the primary acute-rejection outcome through Month 6 and secondary outcomes extending to Month 12 or covering other clinical measures. When several outcomes or time points are examined, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for the collection of tests. A prespecified hierarchy or multiplicity adjustment can address that issue, but the planned approach is not reported in the registry record. The registry lists 20 outcome measures and zero analysis records; it does not identify a testing hierarchy or report adjusted results.

The record labels the primary population as intent to treat, but the definition is incomplete. The complete definition and the handling of participants with missing endpoint data, withdrawal, protocol deviations, or treatment changes are not reported in the registry record. The group-level denominators for the primary outcome are also not reported. Without this information, it is not possible to assess how the analysis population relates to randomized assignment or how missingness might affect the endpoint comparison.

In general, missing outcome data can affect an estimate if the chance of missingness is related to the participant's outcome or treatment group. Statistical approaches may make different assumptions about those missing outcomes; sensitivity analyses can examine whether conclusions depend on those assumptions. This is general context, not a description of analyses performed in this study. The missing-data strategy and any sensitivity analyses are not reported in the registry record.

The registry does describe a within-group confidence-interval method, but it does not report the primary outcome results or a comparative analysis. Consequently, neither multiplicity handling nor missing-data handling can be evaluated against an observed treatment effect.

11. 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: squamous cell carcinoma (13.3%), diarrhoea (11.5%), urinary tract infection (9.1%), pyrexia (7.7%), dehydration (7.7%).

The safety listings give serious adverse-event figures by group as counts of participants affected and participants at risk. For Belatacept - MMF, the listing reports 25 affected among 33 at risk; for Belatacept - SIRO, 19 affected among 26 at risk; and for Tacrolimus - MMF, 22 affected among 30 at risk. The figures for other adverse events are 33 affected among 33 at risk, 26 among 26, and 30 among 30, respectively. These are the registry's reported counts; they should not be treated as rates calculated from a different denominator or as counts of individual event episodes.

The record also lists serious adverse-event terms with percentages: squamous cell carcinoma, 13.3%; diarrhoea, 11.5%; urinary tract infection, 9.1%; pyrexia, 7.7%; dehydration, 7.7%; and hydronephrosis, 7.7%. The denominator and whether these percentages are pooled or group-specific are not reported in the registry record. The listed terms therefore should not be assigned to a particular treatment group or used to compare groups.

Death counts are not reported in the registry record. These safety figures do not establish a causal relationship between a regimen and an event, nor do they replace the missing primary acute-rejection results. The record's duration and methods for collecting adverse events are not reported in the registry information.

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

The record identifies a randomized Phase II comparison of two belatacept-based steroid-free regimens and a tacrolimus-based steroid-free regimen in kidney transplantation. It specifies a clinically defined acute-rejection endpoint through Month 6 and outlines several additional outcomes. These details clarify what the trial was designed to examine, but they do not reveal what the primary outcome showed.

Because the primary endpoint counts, group denominators, comparative estimate, and uncertainty interval are not reported in the registry record, the direction, size, and precision of a treatment difference cannot be assessed. No conclusion that one regimen had fewer or more acute rejections, or that the regimens were similar, follows from the study aim or completed status. A lack of reported results is not evidence that no events occurred.

The study's Phase II designation and enrollment of 93 describe the trial's stage and recorded scale, not the strength or direction of its results. The registry does not report a sample-size justification, so the enrollment figure alone cannot show what effect the study was designed to detect. A planning illustration based on an observed effect, if used, is not observed power and cannot substitute for the actual outcome data.

The safety listings offer some counts and adverse-event terms, but their interpretation is limited by the unreported context for the term percentages and by the absence of death counts. They do not establish that a treatment caused or prevented a listed event. The open-label design is another feature to consider when interpreting outcomes, while the central-pathologist biopsy confirmation is part of the stated acute-rejection definition.

Overall, the registry record provides design and endpoint information but not enough primary outcome data for an efficacy comparison or a quantitative judgment of precision. Further conclusions would require the group-level results and analysis details, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for setting up a three-group randomized comparison while defining a participant-level clinical endpoint. The primary outcome is not simply any clinical suspicion of rejection: the registry describes clinical criteria and biopsy confirmation by a central pathologist. The endpoint also counts each participant once, regardless of multiple episodes, using the worst-graded episode. Those design choices affect what the resulting count would represent.

The open-label, parallel-group design makes clear that treatment assignment was known to participants and investigators. That feature is relevant when considering outcome ascertainment and management, although the registry record does not establish whether it affected the acute-rejection assessment. Randomization supports the purpose of comparing assigned regimens, but does not remove the need to see group results, denominators, uncertainty, and analysis details.

The record also makes a useful distinction between an outcome's existence in a registry and an analysis result. It lists 20 outcome measures, while analysis records are not reported. This matters because outcome descriptions and planned follow-up periods do not answer whether groups differed. The primary endpoint results are not reported in the registry record, so the trial's central comparison cannot be statistically evaluated from the information available.

Finally, the confidence-interval rule illustrates how the method may depend on group size: a normal approximation was used for N at least 5, with an exact method otherwise. The rule offers methodological context, but without the estimates and intervals it cannot convey precision. The trial therefore serves as a reminder that a defined design and statistical method are not substitutes for transparent outcome reporting.

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 trial-specific limitation for interpretation is that the registry record does not report the primary outcome counts, group denominators, or a comparative estimate. Although the endpoint is described in detail, its results through Month 6 cannot be assessed. The same limitation applies to the listed secondary outcomes in the information.

The record reports an overall enrollment of 93 but does not report how participants were distributed among the three groups in the information available for this analysis. It also does not provide the full intent-to-treat definition, missing-data rules, or analysis population counts. These omissions prevent assessment of how all randomized participants were handled and whether incomplete endpoint data could affect a comparison.

The registry characterizes the study as randomized, open-label, multicenter, and parallel-group, but does not report the randomization procedure, concealment method, or detailed analysis plan. The open-label design is relevant context, but the record does not show whether it influenced outcome assessment. Central-pathologist confirmation is included in the endpoint definition; further details of adjudication are not reported.

The sirolimus arm description gives an initial dose but does not report its full subsequent dosing schedule. The record does not report a sample-size justification, multiplicity strategy, or the statistical methods for comparative treatment effects. It lists serious adverse-event figures and terms, but the context and denominator for the term percentages are not reported, and death counts are not reported in the registry record. These gaps limit interpretation of both efficacy and safety comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation — NCT00455013.
• Registry record last updated 2014-06-09; status last verified 2014-05.
• Results first posted 2013-11-21.
• 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

NCT00455013 is a completed randomized, open-label, multicenter, parallel-group Phase II study sponsored by Bristol-Myers Squibb. It enrolled 93 participants and compared belatacept with MMF, belatacept with sirolimus, and tacrolimus with MMF in steroid-free regimens following kidney transplantation.

The primary endpoint was the number of participants with biopsy-confirmed acute rejection from Day 1 to Month 6 in the intent-to-treat population. The registry lists 20 outcome measures and zero analysis records. Primary outcome results, comparative estimates, and the full analysis-population definition are not reported in the registry record. Safety listings include serious adverse-event counts and selected event terms, but their percentage denominators and death counts are not reported.