Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation (NCT01895127), a randomized phase 2 study. The primary outcome is Percent Change in Estimated Glomerular Filtration (eGFR) Rate.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, open-label, parallel-group trial sponsored by Brigham and Women's Hospital. The registry lists an enrollment of 11 and a status of terminated. The start date was 2013-11, and the primary completion date was 2016-04. The reason for termination is not reported in the registry record.

The study summary describes a comparison of eculizumab with plasmapheresis and immunoglobulin for treatment of antibody-mediated rejection in renal transplant recipients. Participants were to be evaluated from AMR diagnosis for 12 months. The primary outcome recorded in the results, however, was percent change in eGFR from week 0 to month 3. A longer follow-up plan does not itself provide evidence about outcomes beyond the posted primary result.

Randomization indicates that allocation was intended to be assigned by chance, while open-label means treatment assignment was not masked. The record does not report the randomization procedure, allocation concealment, or whether outcome assessors were masked. It lists a parallel model, but the primary outcome description also documents treatment crossover or rescue: one participant in the standard-care arm received eculizumab following PP/IVIg, and one participant in the Soliris arm received standard care following completion of Soliris treatment. Both received both treatments before month 3.

The results distinguish Standard of Care, Soliris (Eculizumab), and Standard of Care + Soliris (Eculizumab). This third category matters when reading the outcome estimates: the posted results are not simply a clean comparison of participants who received only their originally assigned approach. The registry record does not report further details about treatment assignment, adherence, protocol deviations, or how the combined-treatment category was handled in an intended randomized comparison.

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.

Screening

Treatment Period (Week 0-Month 3)

Month 3 Follow-up & Biopsy

Long Term Follow-up (Month 3-12)

Analysis population for the primary outcome, as defined in the registry: 1 subject in the SOC arm received rescue therapy, per protocol, with eculizumab following PP/IVIg. 1 subject in the Soliris arm received SOC therapy (PP/IVIg) following completion of Soliris treatment period. Both of these subjects received both SOC and Soliris treatment prior to Month 3 protocol biopsy so we have listed their outcome separately.

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 Percent Change in Estimated Glomerular Filtration (eGFR) Rate, measured over Month 3.

The primary endpoint was percent change in estimated glomerular filtration rate from week 0 to month 3. eGFR is an estimate of kidney filtration based on a calculation rather than a direct measurement of filtration. The registry states that the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used. The endpoint therefore expresses a change in a kidney-function estimate over a defined period after treatment.

Percent change can make change interpretable relative to a participant's starting eGFR, rather than describing only a change in the original measurement units. In general, a group mean summarizes the average change among the participants included in that group; it does not describe every participant's response. A range helps show how widely the individual values extended, but it is not a confidence interval and does not show how precisely the group mean is estimated.

The endpoint is relevant to the study question because AMR occurs after renal transplantation and kidney function is central to evaluating the clinical course. The registry record does not report why this endpoint was selected over other possible measures, how missing measurements were handled, or whether the endpoint was assessed by a blinded evaluator. The reported time point is month 3; the summary's intended evaluation through 12 months does not supply additional primary-endpoint results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies a mean percent change in eGFR and reports a full range for each results group. It does not report a detailed statistical analysis plan, an inferential test, an adjusted model, or a confidence interval for a comparison between treatment strategies. The concepts below explain how to read the reported summaries in general; they do not imply methods that the investigators used.

What does a group mean describe?

In general, a mean is the arithmetic average of the values included in a group. It compresses a set of observations into one central summary, but it does not reveal the shape of the data or how many participants had values close to that average. When a group is small, a single unusually high or low observation can have a substantial effect on the mean. This is relevant to the posted eGFR results because the registry reports small group sizes and wide ranges in some categories.

The reported mean is not a treatment effect by itself. A treatment effect in a randomized study is ordinarily framed as a contrast between assigned groups, with a defined estimand and a measure of uncertainty. The registry record does not report such a contrast for the primary endpoint. Comparing the listed means informally would not account for uncertainty, the treatment crossover described in the outcome population notes, or any analysis choices that may have been made but are not reported.

How should the ranges be read?

The registry describes the dispersion measure as Full Range and reports lower and upper bounds for each group. In general, the range gives the smallest and largest observed values in the data summarized. It shows the span of the observed data but is sensitive to extreme observations and does not describe the distribution between the endpoints. A range is not a standard deviation, standard error, or confidence interval. It should not be read as a margin of error around the mean.

A confidence interval, in general, expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. It can help indicate which effect sizes are compatible with the data, but it is not a guarantee that the true value lies within its limits. No confidence interval for a between-group primary-endpoint comparison is reported in the registry record. The reported full ranges cannot substitute for one.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. When a model assumes less variation than the data contain, uncertainty can be understated, making findings appear more precise than they are. The registry does not report a model for the primary outcome or an assessment of over-dispersion, so it is not possible to determine whether this issue was evaluated. More broadly, the wide observed ranges reinforce the need to be cautious about treating a group mean as a precise summary.

The outcome is a percentage change, and percentage measures can be affected by the baseline value used in the calculation. The record identifies week 0 as the starting point and the modified CKD-EPI equation as the method for estimating eGFR. It does not report details about how baseline values were handled, whether transformations were considered, or whether the analysis accounted for repeated measurements or other covariates. Those choices should not be inferred.

What do the sample-size illustrations mean?

In general, a sample-size calculation asks how many participants a future study might need to detect a specified effect under stated assumptions. The registry-based illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. These are planning illustrations based on the observed result, not the original trial's design justification and not observed power. The trial's own sample-size justification is not reported in the registry record. The illustrations do not remedy the uncertainty of the observed estimates or show that a future study would reproduce the same effect.

The record does not report whether the analysis used an intention-to-treat population, a per-protocol population, or another analysis population. Nor does it explain how the crossover or rescue cases were classified beyond the reported outcome description and results groups. Without those details and a stated comparative analysis, the posted means and ranges are descriptive rather than a basis for formal inference about the randomized treatment strategies.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no posted secondary outcome results. It reports no analyses in the registry. A multiplicity plan—how to control the chance of false-positive findings when testing multiple outcomes, time points, or comparisons—is not reported in the registry record. Because no primary-endpoint hypothesis test or p-value is posted, there is no reported testing procedure to interpret for multiplicity.

Missing-data handling is also not reported in the registry record. The outcome entries give group sizes, but they do not explain whether all randomized participants had month-3 eGFR measurements, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was used. The enrollment entry does not establish how many participants contributed to each outcome estimate, and the participant counts should be read from the outcome entries rather than inferred from enrollment.

The endpoint population description records treatment crossover or rescue before month 3: one participant assigned to standard care received eculizumab following PP/IVIg, and one participant assigned to Soliris received standard care after completing the Soliris treatment period. Both received both treatments before month 3. The registry record does not report an analysis population definition explaining whether participants were analyzed according to original assignment, treatment received, or another rule. It also does not report an analysis addressing the influence of these treatment changes.

Consequently, the posted summaries do not make it possible to assess attrition, missingness patterns, or the robustness of results to alternative analysis populations. These absences matter because the endpoint groups include treatment histories that do not map cleanly to exclusive strategies. No assumption about the direction or size of any resulting bias is justified from the registry record alone.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: antibody-mediated rejection (75.0%), urinary tract infection (50.0%), cellular rejection (42.9%), acute kidney injury (25.0%), hypotension (25.0%).

The safety entries report serious adverse events for Standard of Care and Soliris (Eculizumab). In the standard-care group, 4 participants were at risk and 3 were recorded as affected; in the Soliris group, 7 were at risk and 5 were recorded as affected. The record reports 0 deaths in each group. The entries for other adverse events likewise list 4 at risk and 3 affected for standard care, and 7 at risk and 5 affected for Soliris.

These are counts within the safety groups, not a formal comparison of risk between treatments. The registry does not report a statistical test or confidence interval for a safety contrast. The group sizes are small, and the counts alone do not establish whether an apparent difference is meaningful or attributable to treatment. The safety groups listed do not include the combined-treatment outcome category, and the record does not explain how participants who received both treatments were represented in the safety summaries.

The record lists serious-event terms and percentages, including Antibody-mediated rejection at 75.0%, Urinary Tract Infection at 50.0%, Cellular Rejection at 42.9%, Acute kidney injury at 25.0%, Hypotension at 25.0%, and Pyelonephritis at 25.0%. The record does not provide enough detail to assign these percentages to a specific treatment group or to determine whether terms overlap. An event term may describe an underlying condition or complication; its appearance in a serious-event listing alone does not establish that treatment caused it. The counts should be interpreted as registry safety reporting, not as a causal assessment.

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

The posted results describe month-3 changes in eGFR among participants classified in three outcome groups: Standard of Care, Soliris (Eculizumab), and Standard of Care + Soliris (Eculizumab). The group means and ranges show the observed summaries and the spread of values. They do not, by themselves, answer whether assignment to eculizumab rather than standard care changes eGFR in the broader population of renal transplant recipients with AMR.

That distinction matters because a descriptive group mean is not the same as a randomized treatment comparison. A comparative conclusion requires a defined contrast, an analysis that respects the trial design and treatment history, and an estimate of uncertainty. The registry record does not report a formal between-group estimate, confidence interval, or p-value for the primary outcome. It also documents participants who received both treatment approaches before month 3. The third results category further means that the posted summaries do not represent only two exclusive treatment groups.

The results also do not establish whether an observed change is clinically important. The registry record does not give a threshold for meaningful eGFR change, and the summaries alone do not describe participants' full clinical courses. The planned evaluation through 12 months in the trial summary does not substitute for posted findings at those later times; the primary result reported is at month 3.

Likewise, these data do not establish treatment safety or comparative safety. The safety entries describe affected participants and deaths in the listed groups, but small counts and the absence of comparative uncertainty limit interpretation. Event listings do not prove causation.

The appropriate reading is narrow: the registry reports the observed eGFR summaries and adverse-event counts for this terminated, small phase 2 trial. The data do not establish a definitive benefit, lack of benefit, or harm for either treatment strategy. They also do not justify applying the group summaries to other patients or settings without evidence beyond this record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the difference between a randomized design and a clearly interpretable randomized comparison. The registry identifies random allocation and a parallel model, but the primary outcome results include a category for participants who received both standard care and eculizumab. The endpoint population description also documents treatment crossover or rescue before the month-3 assessment. Treatment assignment and treatment received are therefore not interchangeable when interpreting these summaries.

The small group sizes make descriptive statistics especially sensitive to individual observations. The reported ranges are wide in some groups, while the registry does not report confidence intervals or a comparative analysis. A mean can look precise when written as a single value even when the underlying data are sparse and variable. Reporting the range helps readers recognize spread, but it does not quantify uncertainty in a treatment contrast.

The record also highlights why registration status and posted results should be read together. The trial is listed as terminated, with enrollment of 11, and no analysis is posted in the registry. The record does not give the reason for termination or a statistical analysis plan. That limits the ability to distinguish planned analyses from exploratory summaries and to evaluate how the reported outcome relates to the original design.

For biostatistical interpretation, the main lesson is not to infer a causal effect from a striking group mean or from apparent differences between categories. A valid comparison depends on the estimand, randomized assignment, handling of treatment changes and missing data, and uncertainty around the estimate. Those elements are not fully reported. The results are useful as a record of what was observed, while also demonstrating why transparent analysis details are essential for interpreting small trials.

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 enrollment was 11, and the posted primary outcome groups are small. With sparse observations, summaries can be strongly influenced by individual values, and the ranges indicate considerable spread in some groups. The registry record does not report a formal confidence interval or inferential comparison that would quantify uncertainty in the difference between treatment strategies.

Interpretation is further limited by crossover or rescue before month 3. The endpoint description states that one participant in the standard-care arm received eculizumab after PP/IVIg, and one participant in the Soliris arm received standard care after the Soliris treatment period. Both had received both approaches before month 3. The record does not explain the analysis population or how these cases were handled, and a combined-treatment outcome category is reported separately.

The registry record does not report missing-data methods, the original sample-size justification, a detailed statistical analysis plan, multiplicity control, or a reason for termination. It also does not report secondary outcome results or analyses. Details such as the randomization method, allocation concealment, and outcome-assessor masking are not reported in the registry record. The open-label design is stated, but the implications for measurement or care cannot be assessed from this record alone.

The primary result is at month 3 despite a study summary describing evaluation through 12 months. Later outcome findings are not reported in the registry record. Safety counts are limited and do not include a reported comparative analysis; the listed serious-event percentages are not assigned to treatment groups in the available record. These limitations restrict interpretation to descriptive summaries and do not support a definitive comparative conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation — NCT01895127.
• Registry record last updated 2017-09-21; status last verified 2017-08.
• Results first posted 2017-09-21.
• 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

NCT01895127 is a terminated phase 2 randomized, open-label, parallel trial sponsored by Brigham and Women's Hospital. It studied eculizumab compared with plasmapheresis and immunoglobulin for antibody-mediated rejection following renal transplantation. The registry lists enrollment of 11 and describes evaluation from AMR diagnosis for 12 months.

The primary outcome was percent change in eGFR from week 0 to month 3, using the modified CKD-EPI equation. The posted results report group means and full ranges for Standard of Care, Soliris, and Standard of Care + Soliris. The endpoint description records participants who received both treatment approaches before month 3. No formal between-group analysis, p-value, or confidence interval is reported for the primary outcome.

The registry lists serious and other adverse-event counts for the standard-care and Soliris groups, with 0 deaths in each. Missing-data methods, analysis populations, the reason for termination, and later outcome findings are not reported in the registry record.