Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002) (NCT02663622), a randomized phase 2 study. The primary outcome is Number of Participants Who Experienced an Adverse Event (AE).

2. Clinical Question

3. Trial Design

This was a multicenter, prospective phase II trial described in the registry record as a phase IIa dose-escalation and phase IIa expansion cohort study. Its stated purpose was to evaluate the safety and tolerability of efprezimod alfa as prophylaxis for acute GVHD. The trial is marked completed. The registry record gives a start date of 2016-09-19 and a primary completion date of 2020-06-08.

The design is recorded as randomized, quadruple-masked, and parallel. These labels indicate that treatment assignment was randomized, masking was intended for four categories of people, and participants were assigned to parallel treatment groups rather than crossing between treatments. The specific people masked, random sequence method, allocation concealment procedures, and practical details of masking are not reported in the registry record.

The listed groups were placebo, CD24Fc 240 mg, CD24Fc 480 mg, and CD24Fc 960 mg. Tacrolimus and methotrexate appear in the arm descriptions as accompanying treatments. The 960 mg group is specifically described as multi-dose, with active treatment on Day -1, Day +14, and Day +28; the lower-dose active arms are described as receiving treatment on Day -1. Placebo is described as matching either a single administration or the multi-dose schedule. The arm descriptions in the registry record are incomplete, so additional details of the treatment regimens should not be inferred.

Enrollment is recorded as 44, while the primary safety outcome lists six participants in each of its four groups. A separate adverse-event summary lists the 960 mg multi-dose group with 26 participants at risk. These are different posted summaries and populations; they should not be combined or treated as interchangeable. The registry record does not explain the relationship between the primary endpoint population and the later or expanded safety summary.

Although the trial also lists outcomes concerning acute and chronic GVHD, relapse, non-relapse mortality, infection, overall survival, and GVHD-free and relapse-free survival, the primary outcome discussed in the posted results is an AE count. The record does not provide enough information to reconstruct the complete sequence of dose escalation, expansion, or treatment assignment.

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: The CD24Fc 960 mg arm was initiated alongside the other 3 arms. Once the recommended phase 2 dose (RP2D) was determined, the other 3 arms ceased recruitment but additional participants were recruited into the CD24Fc 960 mg arm. Per FDA request, all participants in the CD24Fc 960 mg arm are considered a single population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who enrolled prior to determination of the recommended phase II dose and received at least one dose of study drug.

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 Participants Who Experienced an Adverse Event (AE), measured over Up to approximately 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 62 days for the CD24Fc 960 mg arm..

The primary endpoint is the number of participants who experienced an adverse event. An AE is defined in the registry record as an untoward medical occurrence in a participant who received study treatment; it does not need to have a causal relationship with that treatment. The endpoint therefore counts participants with at least one qualifying AE, rather than counting every event or measuring the severity of an event.

The reported timeframe extends from one day before HSCT through either 30 or 60 days after HSCT, depending on the treatment arm. The registry’s timeframe description gives approximately 32 days for placebo, CD24Fc 240 mg, and CD24Fc 480 mg, and approximately 62 days for CD24Fc 960 mg. AEs reported after the protocol-specified timeframe were not analyzed for this outcome. Because observation periods differ by arm, the counts should be read within their stated follow-up windows rather than as though every group had identical observation time.

Counting participants with an AE is a straightforward safety summary: it indicates how many people experienced at least one event during the defined period. It does not by itself describe event severity, duration, recurrence, or causal attribution. Nor is it a direct efficacy measure for GVHD prevention. The registry record reports six participants with an AE in each listed primary endpoint group, but does not report an estimable two-arm comparison. The count is therefore descriptive and should not be interpreted as establishing equivalence or a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: a participant either had at least one AE during the defined reporting window or did not. The displayed result is a count of participants with an event. For such data, a comparative analysis would ordinarily contrast the event experience in a treatment group with that in a comparator group. The registry record indicates that values were missing or not estimable for a two-arm comparison, so no such effect estimate should be reconstructed from the posted counts.

What does a count tell the reader?

A count preserves the directly reported number of participants with an event. It does not describe the distribution of multiple events within a participant, and it can conceal differences in event type, seriousness, timing, and duration. For example, the primary outcome groups participants according to whether any AE occurred, while the adverse-event summary separately distinguishes serious AEs and other AEs. These summaries answer related but non-identical safety questions.

General statistical explanation: counts are most informative when considered with their denominators and the outcome definition. The primary endpoint lists six participants in each group, and six experienced an AE in each. The separate safety summary gives its own numbers at risk and serious-event counts, including a larger at-risk group for the CD24Fc 960 mg multi-dose summary. Because the populations and outcome summaries differ, these figures should be kept distinct rather than pooled or added together.

Why are uncertainty intervals useful?

General statistical explanation: an estimate based on a small group can vary substantially from one set of participants to another, even when the underlying event experience is similar. A confidence interval conveys the uncertainty around an estimated effect or event frequency under a statistical model. Wider intervals indicate less precision; narrow intervals indicate greater precision. An interval does not establish that an effect is clinically important, and it does not remove uncertainty about bias or outcome measurement. The registry record does not report confidence intervals for the primary comparison, so its precision cannot be quantified from the posted result.

A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It would not give the probability that a treatment works, nor would it measure the size or importance of an effect. No primary comparative p-value is reported as part of the posted result. Equal observed counts also do not substitute for a formal test, and absence of an estimable comparison should not be reinterpreted as evidence of no difference.

How should different follow-up windows be understood?

General statistical explanation: a simple event count depends in part on the time during which events can be observed. Longer observation can create more opportunity to record an event, even if the underlying risk over time were otherwise similar. Analyses of time-to-event outcomes can account for differing follow-up using methods that incorporate event timing and censoring, but the primary AE endpoint is reported as a participant count within an arm-specific window. The registry record specifies different approximate durations by arm and does not provide a comparative rate analysis for this primary measure.

The record also lists time-to-event outcomes, including acute GVHD-free survival, overall survival, and GVHD-free and relapse-free survival. General statistical explanation: time-to-event methods use the timing of an event and the duration participants remain under observation, rather than treating every participant as if follow-up were identical. Censoring occurs when an individual’s event status is not observed beyond a recorded point. The statistical methods, censoring rules, and detailed estimates for these outcomes are not reported in the registry information summarized for the primary endpoint.

What can planning illustrations establish?

General statistical explanation: sample-size planning translates an assumed effect, significance level, allocation, and statistical model into a target amount of information. The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the assumed detectable effect is a stated fraction of the observed effect. For time-to-event outcomes, the illustrations concern total events; for other outcomes, they concern participants per arm.

Those assumptions describe planning illustrations, not the trial’s original design justification. They are not observed power and do not show that the trial had a particular probability of detecting an effect. The record does not report the trial’s own sample-size justification, and the planning assumptions should not be mistaken for a pre-trial protocol calculation. Where no estimated effect is available, a planning illustration cannot be treated as a substitute for a comparative result.

The registry record reports four analyses and nine posted secondary outcomes. This does not, by itself, specify which outcomes were included in each analysis or whether a particular statistical model was used. The analysis methods for the primary comparison, adjustment covariates, handling of repeated events, and treatment of missing outcome data are not reported in the registry record. Accordingly, the most defensible reading of the primary result is descriptive: the record reports the AE counts and their stated populations and windows, while comparative inference and its precision remain unavailable.

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("Placebo", "CD24Fc 240 mg", "CD24Fc 480 mg", "CD24Fc 960 mg")
n      <- c(6, 6, 6, 6)
events <- c(6, 6, 6, 6)
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  Placebo  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  CD24Fc 240 mg  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  CD24Fc 480 mg  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  CD24Fc 960 mg  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes concerning acute GVHD-free survival, acute and chronic GVHD, relapse, non-relapse mortality, infection, overall survival, and GVHD-free and relapse-free survival. Nine secondary outcomes are posted, and the record reports four analyses. When a trial examines multiple outcomes or comparisons, the chance of at least one apparently unusual result can increase if each is tested separately. General statistical explanation: multiplicity procedures can control the overall error rate or prioritize a prespecified outcome hierarchy. The registry record does not report whether multiplicity was addressed, which outcomes were treated as confirmatory, or whether any hierarchy was used.

The record does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. It also does not report the methods used to handle missing outcome data, loss to follow-up, or incomplete follow-up. These details matter because exclusion, imputation, censoring, and other approaches can affect both estimates and uncertainty. Their absence from the registry record means the analysis cannot be fully reproduced or assessed for sensitivity to missingness.

The primary endpoint population is described as participants enrolled before determination of the recommended phase II dose and who received at least one dose of study drug. The record does not describe an intention-to-treat population for the primary analysis, nor does it report how participants who did not meet that population definition were handled in other outcomes. The primary safety groups each list six participants, while the separate safety summary reports a larger at-risk group for the 960 mg multi-dose regimen. The record does not explain the relationship between those populations. These distinctions should be retained when reading each result rather than assuming all analyses use the same participants.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (16.7%), stomatitis (16.7%), pneumonia (16.7%), weight decreased (16.7%), decreased appetite (16.7%).

The adverse-event summary reports serious AEs in two of six participants at risk in the placebo group, two of six in the CD24Fc 240 mg group, one of six in the CD24Fc 480 mg group, and twelve of 26 in the CD24Fc 960 mg multi-dose group. It reports other AEs in six of six, six of six, six of six, and 26 of 26 participants at risk, respectively. These are counts from the safety summary and should not be substituted for the primary endpoint results without noting the separate reporting context.

The record also lists deaths in the safety groups: three for placebo, one for CD24Fc 240 mg, one for CD24Fc 480 mg, and eight for CD24Fc 960 mg multi-dose. These counts do not establish that deaths were caused by study treatment. The registry record does not provide causal attribution for these figures in the summary.

The serious-event terms listed among the top terms are nausea, stomatitis, pneumonia, weight decreased, decreased appetite, and dehydration, each reported as 16.7%. The listing does not establish that each term occurred in every treatment group or identify a group-specific rate. Serious AE counts, other AE counts, and death counts describe different safety summaries; they should be read as descriptive observations, not as adjusted comparisons or causal estimates.

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

The posted primary result establishes that the registry recorded an AE for six participants in each of the placebo, CD24Fc 240 mg, CD24Fc 480 mg, and CD24Fc 960 mg primary endpoint groups. The endpoint definition includes any untoward medical occurrence during the specified period and does not require a causal link to treatment. This is useful descriptive safety information, but it is not a comparison of treatment effects with quantified precision.

The result does not establish that the regimens have identical safety, that an AE was caused by efprezimod alfa, or that no clinically important difference exists. A finding of equal counts is not an equivalence analysis. Establishing equivalence or non-inferiority would require a prespecified margin and an appropriate comparative analysis; these are not reported in the registry record. The record also does not report an estimable two-arm primary comparison or its confidence interval.

The result does not answer whether efprezimod alfa prevents acute GVHD. Although prevention is the clinical aim and GVHD outcomes are among the listed secondary outcomes, the primary outcome is AE occurrence. The primary AE counts cannot be used as evidence of an effect on GVHD, relapse, survival, infection, or other outcomes. Those require their own outcome definitions, analysis populations, estimates, and uncertainty measures.

Safety figures require additional care because follow-up windows differ by arm and the primary endpoint group counts do not align in description with all counts in the separate adverse-event summary. The latter reports serious events, other AEs, deaths, and selected serious-event terms. Such summaries can identify what was recorded, but without comparative methods, fuller event details, and attribution information, they do not support causal conclusions.

In short, the registry record documents safety observations in a randomized phase II trial but leaves important uncertainty about comparative effects and their precision. The data should be interpreted as descriptive results from the populations and timeframes stated, not as proof for or against a treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clinical objective and a primary endpoint. The study aimed to evaluate efprezimod alfa for acute GVHD prophylaxis, but its primary outcome counted participants with an AE. A safety endpoint can characterize harms observed during treatment and follow-up; it does not directly quantify prevention of the target condition. Readers need to keep the endpoint question separate from the broader reason the study was conducted.

The record also illustrates why population definitions and follow-up windows matter. The primary outcome is limited to participants enrolled before determination of the recommended phase II dose who received at least one dose, and its observation period differs by arm. The separate safety summary has a different reported at-risk count for the multi-dose group. Treating these summaries as a single analysis could obscure who contributed to each result and how long outcomes were observed.

Small descriptive groups make precision particularly important. The primary counts are the same in all four listed groups, but the registry does not report an estimable comparative effect or confidence interval. Without these, readers cannot judge the range of comparative effects compatible with the observations. Nor can they infer equivalence from matching counts. A clear statement of uncertainty is central to responsible interpretation, especially when the record includes multiple clinical outcomes.

Finally, the trial record lists several secondary outcomes and planning assumptions, but does not report the full analysis strategy, missing-data handling, multiplicity procedures, or the original sample-size justification. This limits reproducibility and makes it difficult to distinguish confirmatory from exploratory findings. These are not merely reporting details: they determine how estimates should be interpreted and how strongly conclusions can be drawn.

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.

The primary AE groups are small as reported, with six participants listed in each group, and the registry does not provide a comparative estimate or uncertainty interval for the primary binary endpoint. Counts alone therefore give limited information about precision. The trial’s enrollment is recorded as 44, but the relationship between that enrollment and the primary endpoint population is not explained in the registry record.

Observation windows differ across the groups: approximately 32 days for placebo and the 240 mg and 480 mg arms, and approximately 62 days for the 960 mg arm. Raw counts collected over different periods are not directly equivalent to rates over a common duration. The registry record does not report a rate-based comparison for the primary outcome.

The separate safety summary lists a larger at-risk group for the CD24Fc 960 mg multi-dose regimen than the primary endpoint summary. The record does not explain the population difference or provide enough detail to reconcile the summaries. Arm descriptions are also incomplete, limiting assessment of the treatment schedules beyond the stated administrations and background treatments.

Important methods are not reported in the registry record, including the randomization procedure, the statistical analysis plan, the sample-size justification, multiplicity handling, interim analyses, and missing-data methods. The record does not give enough comparative detail to interpret selected serious-event terms by group or establish causal attribution for deaths and AEs. These limitations constrain conclusions about comparative safety, efficacy, and the precision of any effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002) — NCT02663622.
• Registry record last updated 2024-01-23; status last verified 2024-01.
• Results first posted 2021-06-18.
• 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, randomized, quadruple-masked, parallel phase II trial of efprezimod alfa for acute GVHD prophylaxis following myeloablative allogeneic HSCT. It lists placebo and CD24Fc 240 mg, 480 mg, and 960 mg groups, with tacrolimus and methotrexate included in the arm descriptions. Enrollment is recorded as 44.

The primary endpoint counts participants experiencing an AE within the specified, arm-dependent timeframe. The posted primary counts are six in each listed group; a two-arm comparison is not reported as estimable. The separate safety summary includes serious AE counts, other AE counts, death counts, and selected serious-event terms. The registry record does not provide sufficient comparative estimates or methods to establish causal effects or quantify the precision of the primary result.