Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD (NCT02406651), a na phase 1, phase 2 study. The primary outcome is The Number of Participants With Lower Gastrointestinal Acute Graft-Versus-Host-Disease Treatment Response Rate on Day 28.

2. Clinical Question

In statistical terms, the central question is descriptive: how many participants in this treated group met the stated response criterion at the specified assessment time? Without a control group, the study cannot estimate a randomized treatment contrast. Its findings, if reported, would characterize outcomes observed in this group under the combined treatment and study conditions.

3. Trial Design

The registry describes a completed Phase IIa, single-arm, open-label study of F-652 in combination with systemic corticosteroids. The official title identifies recipients of hematopoietic stem cell transplantation with newly diagnosed grade II-IV lower gastrointestinal acute graft-versus-host disease. The registry lists the phase fields as PHASE1 and PHASE2, while the study description calls it Phase IIa.

There was no randomized allocation and no masking. The study model is single-group, so participants received F-652 concurrently with systemic corticosteroids rather than being assigned to contrasting arms. The listed regimen was one F-652 dose per week for four weeks. Planned follow-up visits were on days 28, 56, 180 and 365 after treatment, with the primary response assessment specified for day 28 after the first F-652 treatment.

The record gives an enrollment of 30. Its primary-outcome population description adds that 30 participants were dosed based on initial screening; three were removed after receiving one dose because they failed inclusion or exclusion criteria, leaving 27 to continue in the study. It also states that all participants were exposed to study drug. These statements describe different points in enrollment and continuation, but the registry record does not explain how the primary response denominator was defined or how the removed participants were handled in the endpoint analysis.

The study is marked completed, with a start date of 2016-05-12 and a primary completion date of 2019-04-09. These dates describe the study record and do not establish when particular outcomes were assessed or analyzed beyond the timeframes stated for those outcomes. A detailed protocol, sample-size justification, planned interim analyses and full statistical analysis plan are not reported in the registry record. The record's design supports descriptive observations from the treated group, but not a randomized estimate of the effect of adding F-652 to corticosteroids.

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: 30 participants were dosed based on initial screening. Then 3 of the 30 participants were removed after receiving one dose because they failed inclusion/exclusion criteria leaving 27 participants to continue in the study. All participants were exposed to 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.

Population: 30 participants were dosed based on initial screening. Then 3 of the 30 participants were removed after receiving one dose because they failed inclusion/exclusion criteria leaving 27 participants to continue in the study. The baseline demographics were assessed based on the total initial enrolled number of participants (30). All 30 participants were exposed to study drug so they were in the safety population, but not all were in the efficacy as they did not continue in the study per protocol.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants With Lower Gastrointestinal Acute Graft-Versus-Host-Disease Treatment Response Rate on Day 28, measured over 28 days after first treatment of F-652.

The primary endpoint is the number of participants with a lower gastrointestinal acute graft-versus-host-disease treatment response on day 28 after the first F-652 treatment. It is a count endpoint: it records how many participants met the study's response definition by the specified assessment time. The registry gives the endpoint title and description, but does not include the response count or the operational definition of response in the registry record for this analysis. The response result is therefore not reported in the registry record.

A response endpoint is used to summarize whether participants reached a defined clinical status at a particular time. A count can be straightforward to interpret when its response criteria, denominator, and handling of missing assessments are clear. Those details matter because the number meeting the criterion alone does not describe how many participants were assessed, how unassessed participants were treated in the analysis, or how uncertain the estimate is.

Here, the registry's population description distinguishes 30 participants dosed from 27 who continued after three were removed for failing inclusion or exclusion criteria. It does not state which denominator was used for the primary response result, nor does it provide the result itself. The endpoint title indicates a day-28 assessment, while the timeframe says 28 days after the first F-652 treatment. The record also lists other response assessments at days 14, 28 and 56 for overall aGVHD, and days 14 and 56 for lower GI aGVHD. These are additional outcome questions, not substitutes for the unreported primary count.

Because this is a single-group study, the endpoint can describe response in the participants studied, but it cannot by itself establish how outcomes would differ under a separate comparator condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What a count endpoint represents. The primary outcome is a count of participants meeting a response criterion at a defined time. In general, a count is most interpretable alongside a clear denominator and a stated rule for determining response. Here the assessment time is day 28 after the first F-652 treatment, but the response count is not reported in the registry record. The registry also does not describe the response criteria in the registry record for this analysis. Therefore, no estimate of the frequency of response can be interpreted from the record.

Descriptive analysis and comparison. In a single-group study, a count or proportion can describe outcomes among the treated participants. A randomized comparison would instead assess how outcomes differ between assigned groups, which helps separate a treatment contrast from differences in participant mix and other influences. This study has no separate comparator group: its allocation is listed as NA and its model as single-group. General statistical reasoning therefore supports descriptive interpretation, not a causal comparison of F-652 with an alternative. Since the primary outcome value is absent, even a descriptive response estimate cannot be made from the registry record.

Precision and confidence intervals. A confidence interval is a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; a wider interval generally indicates less precision. For a binary outcome, such as whether a participant met a response definition, interval methods account for the fact that the estimate is based on a finite group. No primary response estimate or confidence interval is reported in the registry record, so the precision of the primary result cannot be assessed. General concepts about intervals do not supply missing study results.

Planning illustrations are not observed power. The stated sample-size assumptions describe a planning illustration based on the observed effect, rather than the trial's own design. Those assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. The illustration is not evidence that the trial had a particular probability of finding a result, and it is not observed power. In general, planning calculations depend on the effect size, variability or event frequency, allocation, and chosen error rate. The trial itself is single-group, so the equal-allocation, two-arm planning assumptions do not describe its actual design. No sample-size justification for the trial is reported in the registry record.

Why a two-arm calculation does not create a comparator. A statistical illustration can describe the sample sizes that might be needed for a hypothetical two-arm study under stated assumptions. It cannot turn a single-group study into a comparative trial. In this study, no like-for-like control group is reported. Any planning numbers associated with a hypothetical comparison should be read only as planning illustrations, not as observed group differences or as evidence about the efficacy of the regimen.

Over-dispersion in general. Over-dispersion occurs when observed variability exceeds what a statistical model assumes. When present, standard errors from an overly restrictive model can be too small, making estimates appear more precise than warranted. This is a general consideration for outcomes modeled as counts or rates. The primary endpoint is a count of participants, not a count of repeated events per participant, and the registry does not report a model or estimate for it. No claim about over-dispersion in this study can be made from the record.

Multiple outcomes and assessments. The registry lists five outcome measures in total, including lower GI response at days 14 and 56, overall response at days 14, 28 and 56, immunosuppressive medication discontinuation at day 180 and one year, overall survival at one year, and the primary day-28 lower GI response measure. Considering multiple endpoints or assessment times can increase the chance of at least one apparently unusual result if each is tested separately. General statistical practice may address this through a prespecified testing sequence or adjustment, depending on the aims. A multiplicity plan and the results of statistical tests are not reported in the registry record. The listed outcomes alone do not reveal whether adjustment was intended or performed.

Analysis populations and participant flow. The registry says 30 participants were dosed based on initial screening; three were removed after one dose for failing inclusion or exclusion criteria, leaving 27 to continue. All participants were exposed to study drug. These are relevant details for understanding who entered and continued in the study, but they do not identify the primary analysis population or establish the denominator used for the response endpoint. In general, an analysis population should be defined in advance and applied consistently, with exclusions and missing assessments handled according to a stated approach. Those details are not reported in the registry record.

Missing observations and time-to-event outcomes. Missing outcome data can affect a result if participants with unavailable assessments differ from those whose outcomes are recorded. A transparent analysis describes how missing assessments were counted or modeled and tests whether conclusions depend on those choices. The registry does not report a missing-data method. It lists overall survival at one year as a secondary outcome, but the registry entries do not include a survival estimate, event-time analysis, or method. The presence of a follow-up timeframe does not reveal how incomplete follow-up was handled.

What the posted statistical information supports. The registry lists no analyses in the registry record for this assessment. It describes the endpoint, the treatment schedule, the participant flow, the outcome timeframes, planning assumptions, and selected safety counts. Without reported endpoint values, analysis methods, and uncertainty estimates, statistical interpretation is necessarily limited to the design and information explicitly recorded. This distinction keeps planned assessments separate from results and avoids treating a planning calculation as evidence from participants.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes and assessment times: lower GI response at days 14 and 56; overall aGVHD response at days 14, 28 and 56; discontinuation of immunosuppressive medication at day 180 and one year; and overall survival at one year, in addition to the primary day-28 lower GI response measure. Evaluating many outcomes can raise multiplicity concerns when statistical tests are used, because more tests create more opportunities for a result to appear notable by chance. The registry record does not report a multiplicity strategy, a hierarchy of endpoints, or whether the listed outcomes were analyzed with formal tests.

The primary outcome population description states that 30 participants were dosed and that three were removed after one dose for failing inclusion or exclusion criteria, leaving 27 to continue. It also says that all participants were exposed to study drug. The record does not state which analysis population was used for the primary endpoint, how the removed participants were handled, or what denominator would apply to the response count.

A missing-data method is not reported in the registry record. That absence matters because an endpoint result depends not only on observed responses, but also on how participants without an assessment are treated. The registry does not describe an imputation method, a sensitivity analysis, or another approach to missing assessments. A detailed statistical analysis plan and interim-analysis information are also not reported in the registry record. These gaps prevent assessment of whether the planned analysis addressed multiplicity, exclusions, and incomplete follow-up in a prespecified way.

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: sepsis (6.7%), devise related infection (6.7%), klebsiella infection (6.7%), enterocolitis (3.3%), pyrexia (3.3%).

The registry reports that 10 of 30 participants in the F-652 and systemic corticosteroids group were affected by serious adverse events, while 26 of 30 were affected by other adverse events. It lists 4 deaths. These are participant counts in the treated group; they are not comparisons against a control group. The registry record does not establish that any listed event or death was caused by F-652 or by the combined regimen.

The most frequent serious-event terms listed are sepsis and “devise related infection,” each at 6.7%. Klebsiella infection is also listed at 6.7%; enterocolitis, pyrexia and streptococcal pneumonia are each listed at 3.3%. These percentages are reproduced as recorded. The registry entries do not explain whether participants could contribute more than one term, how terms were coded, or whether the listed percentages use the full group as their denominator. They should therefore be read as registry-reported event descriptions, not as an independent estimate of risk.

In general, adverse-event counts describe events observed during a defined study period and do not alone establish causation. Interpretation also depends on timing, severity definitions, exposure, underlying disease, concomitant treatment and follow-up. A single-group study cannot provide a randomized comparison of safety rates. The counts are relevant descriptive information, but the registry record does not report a comparative safety analysis.

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

The record documents a completed, open-label, single-group study in which F-652 was given with systemic corticosteroids to recipients of hematopoietic stem cell transplantation with newly diagnosed grade II-IV lower GI acute graft-versus-host disease. It describes the dosing schedule, follow-up timeframes, primary response question, secondary outcomes, participant flow and selected adverse-event counts. This information clarifies the design and the kinds of outcomes the study set out to assess.

The record does not report the primary response count. It also does not report secondary outcome results in the registry record for this analysis, or a statistical analysis of those outcomes. Consequently, the posted information cannot quantify the observed primary response, describe its precision, or establish a statistical association for the listed secondary outcomes. The stated enrollment and continuation counts are not substitutes for endpoint results.

The absence of a comparator is another central constraint. Any outcomes from this group would describe participants receiving F-652 with systemic corticosteroids under the study conditions. They could not, by themselves, show what would have happened to comparable participants under a different treatment condition, nor isolate the contribution of F-652 from corticosteroids and other influences. The study design is not a randomized comparison.

The serious and other adverse-event counts, death count, and listed serious-event terms provide descriptive safety information. They do not establish causation or comparative risk. The registry record also does not report the statistical plan, missing-data handling, analysis population, or multiplicity approach needed to assess those aspects of the evidence.

Thus, the record supports an account of the study's structure and recorded safety counts, but not a numerical conclusion about the primary response or a comparative treatment effect. The lack of an endpoint count should be distinguished from evidence of no response: the result is not reported in the registry record. Likewise, the design limitation is not a finding that the regimen is ineffective; it means that a causal treatment contrast is not available from this single-group study.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design determines the kinds of conclusions a study can support. The registry identifies a clinically focused response question and a defined assessment time, while using an open-label, single-group design. Such a study can describe outcomes among participants who received the combined regimen, but it lacks a randomized comparator for estimating a treatment contrast. That distinction is essential when interpreting response counts and safety observations.

Participant flow also matters. The record describes 30 participants dosed and three later removed after one dose for failing inclusion or exclusion criteria, with 27 continuing. It states that all participants were exposed to study drug, but does not identify the denominator used for the primary endpoint. This makes clear why an endpoint count should be accompanied by an explicit analysis population and rules for exclusions.

The listed outcome set covers response at multiple timepoints, medication discontinuation and survival. Multiple outcomes can be useful for characterizing different aspects of a study, but they raise questions about prespecification and multiplicity when formal testing is performed. The registry record does not state how these issues were handled. Nor does it report the primary response value, so there is no estimate whose precision or consistency across outcomes can be assessed.

The safety record illustrates another statistical distinction: event counts describe what was recorded, whereas comparative rates and causal attribution require additional design and analytic information. The serious adverse-event and other adverse-event counts are useful descriptive details, but do not establish what would occur under a different treatment condition.

Finally, the planning assumptions should be kept separate from the study's actual design and findings. A hypothetical two-arm sample-size illustration does not create a control group and is not observed power. The record is therefore useful for teaching careful separation of study intent, design, participant flow, planning assumptions and reported results.

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 main limitation for interpreting efficacy is that the primary endpoint value is not reported in the registry record. The registry gives a response question and assessment time, but no response count, uncertainty estimate or statistical test. The listed secondary outcomes also lack results in the registry record for this analysis. This prevents quantitative assessment of the study's clinical response findings.

The single-group, open-label design has no randomized comparator. Any outcomes could describe the treated participants, but would not isolate the contribution of F-652 from systemic corticosteroids or other influences. The study also cannot provide a like-for-like randomized comparison of adverse events. Because masking is listed as none, outcome assessment was not masked according to the registry design information.

The participant counts require care: 30 were dosed based on initial screening, three were removed after one dose for failing inclusion or exclusion criteria, and 27 continued. The registry also says all participants were exposed to study drug. It does not state the primary analysis denominator or how removed participants were handled for the endpoint. Missing-data procedures and the analysis population are not reported in the registry record.

The record does not report a detailed statistical plan, the rationale for the enrollment target, any interim analyses, multiplicity handling, or an analysis of the primary endpoint. It also does not provide the operational response definition in the registry record. These omissions limit reproducibility and make it difficult to evaluate how planned methods corresponded to the recorded outcome.

Safety interpretation is limited by the absence of a comparator and by the lack of detail on event timing, coding and attribution in the registry record for this analysis. The reported counts and terms are descriptive and do not establish causation. These limitations are specific to the information and design recorded; they should not be mistaken for evidence that an unreported endpoint had a particular value.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD — NCT02406651.
• Registry record last updated 2021-07-22; status last verified 2021-07.
• Results first posted 2021-07-22.
• 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 a completed Phase IIa, open-label, single-group study of F-652 given with systemic corticosteroids for newly diagnosed grade II-IV lower GI acute graft-versus-host disease after hematopoietic stem cell transplantation. The regimen called for F-652 once a week for four weeks. Enrollment was 30; the record says three participants were removed after one dose for failing inclusion or exclusion criteria, leaving 27 to continue, and that all participants were exposed to study drug.

The primary endpoint was the number of participants with lower GI treatment response on day 28 after the first F-652 treatment. Its result is not reported in the registry record. The record lists secondary response, immunosuppressive-medication discontinuation and survival outcomes, but their results are not included in the registry record for this analysis. It reports 10 of 30 participants affected by serious adverse events, 26 of 30 by other adverse events, and 4 deaths. The single-group design does not provide a randomized treatment comparison, and the registry record does not report a full statistical analysis, missing-data method or multiplicity plan.