Exploratory Safety Study of ALD518 in Subjects With Steroid-refractory Acute Graft Versus Host Disease (GVHD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploratory Safety Study of ALD518 in Subjects With Steroid-refractory Acute Graft Versus Host Disease (GVHD) (NCT01530256), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events, Including Infections and Loss of Engraftment.

2. Clinical Question

The study title identifies it as an exploratory safety study in subjects with steroid-refractory acute GVHD. Its brief description also says the purpose was to identify doses for possible further investigation. Those aims combine safety and dose exploration, but the record does not describe the dose-selection rules or how biological activity and potential effectiveness were to be evaluated.

With a single group and no comparator, the study could describe events observed among participants receiving ALD518, but the design does not separate events associated with the intervention from events related to the underlying disease, transplant, other care, or chance. The record does not report the information needed to make that distinction. Its central documented question is therefore descriptive safety, not comparative effectiveness.

3. Trial Design

This was a Phase 1/2 study of ALD518 in people with glucocorticoid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplant. The registry lists a single-group model, allocation as NA, and no masking. Enrollment is recorded as 3. The sponsor is CSL Behring. The start is recorded as 2012-03, primary completion as 2013-03, and status as terminated.

The study purpose was to determine safe and tolerable, biologically active, potentially effective dose or doses for further investigation in Part B. The intervention entries identify ALD518, but the dose levels, administration details, and reason for termination are not reported in the registry record. The listed arm description contains no further description. It is therefore not possible to infer from the record how the intervention was administered or how any dose was selected.

A single-group study does not include a concurrent control group for estimating a treatment contrast. The registry’s allocation entry is NA, consistent with there being no randomized allocation described. No masking is listed. These features matter because observations in the ALD518 group cannot be compared against a randomized control group to account for differences in prognosis, concurrent care, or other influences.

The registry records five outcome measures and lists secondary outcomes concerning relapse of underlying malignant disease, overall survival, and change in patient-reported outcomes measured by the FACT-BMT questionnaire. The primary outcome is the number of participants with adverse events, including infections and loss of engraftment, through Week 24. No outcome analyses are listed. Thus, the record describes intended outcome monitoring but does not provide analyzed findings for those outcomes.

Although the registry describes the project as Phase 1/2 and refers to potential further investigation in Part B, details of any phases, dose cohorts, or progression rules are not reported in the registry record. The study’s status is terminated; the record does not explain why it ended or what conclusions the sponsor drew.

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 trial was terminated after only 3 participants received the 160 mg dose.

Overall Study

Reasons for not completing this period:

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 With Adverse Events, Including Infections and Loss of Engraftment, measured over Through Week 24.

The primary endpoint is the number of participants with adverse events, including infections and loss of engraftment, through Week 24. It is recorded as a participant count. In a safety-focused study, counting participants who experience specified types of events can describe how many people had an event during the stated observation period. The inclusion of infections and loss of engraftment reflects the endpoint’s stated safety scope in the setting of acute GVHD after transplant.

This type of endpoint is useful for organizing safety observations, but a count alone does not describe event severity, duration, recurrence, timing, or whether an event was considered related to the intervention. Those details would require corresponding definitions and results. They are not reported in the registry record for the primary outcome.

The record gives the endpoint and its timeframe, but it does not report an analyzed primary result. It also does not report a participant-level analysis population, the number with the primary outcome, or details of how missing follow-up was handled. Consequently, the endpoint description identifies what the study planned to count, rather than providing an interpretable estimate of the frequency of primary-outcome events.

General statistical explanation: participant counts are straightforward to interpret as counts, but their precision depends on how many participants contribute information and on the number of events observed. Counts do not by themselves establish causation. In a single-group study, they describe events in the observed group and cannot provide a randomized comparison of risks.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group Phase 1/2 trial with no masking and allocation recorded as NA. It names a participant-count safety endpoint through Week 24, but lists no outcome analyses. Statistical interpretation must therefore distinguish the design and planned measurement from analyzed results: the endpoint tells readers what was to be counted, while the record does not report a statistical estimate for that endpoint.

What does a participant count describe?

General statistical explanation: a count records the number of participants meeting an outcome definition. It is not the same as an event rate unless the relevant denominator and observation period are also clear. The primary endpoint specifies participants with adverse events, including infections and loss of engraftment, and gives a timeframe of through Week 24. The record does not provide the analyzed count for that endpoint or explain how participants with incomplete follow-up were treated.

Counts are often useful in exploratory safety monitoring because they make observed events visible without requiring a complex model. However, counts alone do not show when events occurred, whether one participant had more than one event, whether events were related to treatment, or whether the same event was included in more than one category. Those details are not reported for the primary outcome in the registry record.

Why does the single-group design matter?

General statistical explanation: a control group supports a comparative estimate by providing an outcome distribution under a different condition. In a randomized trial, random allocation can help balance both known and unknown prognostic factors between groups, although it does not guarantee perfect balance. This study is listed as single group, with allocation NA; there is no like-for-like control comparison. As a result, any event count in the ALD518 group would be descriptive and could not by itself identify what would have happened to comparable participants without ALD518.

Because no masking is listed, the record does not describe blinded outcome assessment. For objectively defined events, masking may be less influential than for outcomes involving judgment, but the registry does not provide enough information about event definitions or ascertainment to assess that issue for this study. This is a general methodological consideration, not a claim about how events were assessed.

How should percentages and event summaries be read?

The registry’s adverse-event summary gives serious-event and other-event counts, along with percentages for listed serious-event terms. A percentage is a descriptive proportion as recorded, not a measure of causal effect. With a very small enrolled group, an observation from one participant can have a large effect on a proportion. General statistical explanation: confidence intervals can express uncertainty around proportions, but they are not reported for the primary endpoint in the registry record. Even a narrow or wide interval would not address confounding or establish that an event was caused by the intervention.

Serious adverse events and the primary endpoint should not automatically be treated as identical summaries. The primary endpoint names adverse events, including infections and loss of engraftment, while the adverse-event listing separately summarizes serious and other events. The registry does not report definitions or an explicit mapping between those summaries and the primary endpoint. Caution is warranted when comparing or combining them.

What do the planning illustrations mean?

General statistical explanation: sample-size planning asks how many participants might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. The planning description associated with this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says the target effect is a stated fraction of the observed effect. For time-to-event planning, it refers to a total number of events using the Schoenfeld approach; for other outcomes, it refers to participants per arm.

Those assumptions do not describe this trial’s single-group design, and the registry record does not report a randomized two-arm comparison. Any such values are planning illustrations, not evidence of the trial’s achieved precision or observed power. They do not establish that the study was adequately sized, and they should not be read as results from this study. The observed effect used for planning is not accompanied by an analyzed primary outcome in the registry record.

What can be said about statistical significance?

The registry record lists no outcome analyses and does not provide a primary outcome test, confidence interval, or inferential model. A p-value therefore cannot be interpreted for the primary endpoint from the record. General statistical explanation: a p-value, when calculated under a stated model, describes how compatible the observed data are with a specified null hypothesis; it does not measure the probability that a treatment works or that the null hypothesis is true. Without a reported analysis and its assumptions, significance language would be unwarranted.

More broadly, statistical methods depend on prespecified outcome definitions, analysis populations, handling of incomplete data, and a clear plan for multiple outcomes. These details are not reported in the registry record. The lack of reported analyses prevents assessment of whether the planned methods were followed or whether conclusions were based on any particular analysis population.

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("ALD518")
n      <- c(3)
events <- c(3)
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  ALD518  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes concerning relapse of underlying malignant disease, overall survival, and change in FACT-BMT questionnaire score. It also records five outcome measures. No outcome analyses are listed. The analysis plan, including any hierarchy among outcomes, adjustment for multiple testing, or decision rules for interpreting secondary outcomes, is not reported in the registry record.

General statistical explanation: when multiple outcomes or repeated tests are examined, the chance of finding at least one apparently notable result can increase if each is interpreted without accounting for the broader set of tests. A prespecified hierarchy or multiplicity adjustment can help clarify how evidence should be judged. The record does not describe whether such procedures were planned, so no claim about multiplicity control is possible.

The record does not report a primary endpoint analysis population or specify how participants with missing outcome observations were handled. It also does not provide missing-data counts, reasons for missingness, or sensitivity analyses. General statistical explanation: incomplete follow-up can affect an estimate if the people whose outcomes are missing differ systematically from those whose outcomes are observed. Methods for addressing missing data require assumptions, and those assumptions should be described when results are presented.

These omissions make it difficult to evaluate the completeness and robustness of any outcome interpretation. The status is terminated, but the reason for termination and any analysis conducted outside the posted registry results are not reported in the registry record. The listed counts should therefore be read as registry summaries, not as a substitute for a documented analysis plan or complete outcome report.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: renal failure acute (66.7%), sepsis (33.3%), retinal detachment (33.3%), sinusitis (33.3%), fungal infection (33.3%).

The serious-event summary lists 3 at risk and 3 affected; the other adverse-event summary also lists 3 at risk and 3 affected. The record lists 2 deaths. These are descriptive figures. The registry does not report the causes or timing of deaths, or whether they were considered related to ALD518. It also does not explain how the adverse-event summaries relate to the primary endpoint’s definition or its through Week 24 timeframe.

The listed serious-event terms are Renal failure acute at 66.7%, Sepsis at 33.3%, Retinal detachment at 33.3%, Sinusitis at 33.3%, and Fungal infection at 33.3%. These percentages should be read as reported summaries of the terms, not as evidence of treatment causation. The registry does not provide event-level details, including whether a participant could contribute to more than one term, the duration or severity of events, or the sponsor’s attribution assessments.

General statistical explanation: percentages based on very small groups are unstable descriptions; each observed participant can substantially influence them. The percentages do not provide a comparison with another treatment or a background rate. They should be interpreted alongside the study’s single-group design and the absence of reported outcome analyses, rather than as estimates of comparative risk.

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

The registry record documents an exploratory safety study of ALD518 in people with glucocorticoid-refractory acute GVHD after allogeneic hematopoietic stem cell transplant. It records a single-group Phase 1/2 design, enrollment of 3, a primary endpoint counting participants with adverse events through Week 24, and a terminated status. It also includes adverse-event summaries and lists secondary outcomes.

What the record does not provide is an analyzed result for the primary endpoint. It does not give a primary endpoint estimate, confidence interval, or statistical test. Nor does it report analyses of relapse, overall survival, or FACT-BMT changes. The serious-event terms and counts offer descriptive safety information, but they do not show whether ALD518 caused the events or how the experience compares with another treatment or control condition.

The study’s stated purpose was dose exploration for possible further investigation. The registry does not report dose levels, dose-specific findings, or criteria used to decide whether a dose was safe, tolerable, or biologically active. The record therefore cannot support conclusions about dose selection or the results of any later investigation.

General statistical explanation: an observed event count is not equivalent to a causal effect. Causal interpretation generally requires a suitable comparison and assumptions about how participants entered and were followed in each group. A single-group summary cannot account for differences that might have occurred in the absence of the intervention. Likewise, lack of a reported analysis is not evidence that no events occurred; it means the registry record does not present an analyzed primary endpoint result.

The record supports a narrow conclusion about what was registered and what summaries were posted: the trial was exploratory, single group, small in enrollment, and terminated, with no listed outcome analyses. It does not establish efficacy, lack of efficacy, or a causal safety profile. Those conclusions would require complete analyzed results and, for comparative claims, evidence from an appropriate comparison.

14. Why This Trial Matters Statistically

This trial matters statistically because its design and reporting illustrate the distinction between an exploratory safety objective and a comparative treatment-effect question. The registry identifies a single group and no masking. Those features may permit observation of events during exposure, but they do not create a control-based estimate of what would have happened under another condition.

The enrollment of 3 also makes the limits of descriptive summaries especially important. General statistical explanation: when a group is small, estimates based on participant counts can be sensitive to individual outcomes, and uncertainty is hard to characterize precisely. The registry’s serious-event percentages should therefore be treated as descriptions of the posted record, not as stable estimates of broader event probabilities.

The primary endpoint is framed as a count of participants with adverse events through Week 24, but no analyzed primary outcome is listed. This distinction is important for readers: a registered endpoint is evidence of what investigators intended to measure, not proof that an estimate or complete analysis was reported. The gap between outcome definition and outcome results limits reproducibility and makes interpretation more cautious.

The stated aim included identifying doses for further investigation. For dose-finding conclusions to be evaluated, readers would need dose-specific exposure and outcome information, as well as the rules used to interpret safety and biological activity. These details are not reported in the registry record. The study therefore raises a practical statistical lesson: exploratory aims need transparent outcome reporting and clear decision criteria if their results are to inform later research.

Finally, the record’s planning assumptions refer to a two-arm design even though the registered trial is single group. This reinforces why planning illustrations must be read according to their assumptions and not mistaken for observed power or a result from the actual trial. Statistical interpretation depends on alignment between the design, the analysis, and the question being asked.

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.

Several trial-specific limitations constrain interpretation. The record describes a single-group study with no masking and allocation recorded as NA. There is no comparator, so posted outcomes cannot establish a relative difference between ALD518 and another condition. The absence of masking may also matter for outcome assessment, but the registry does not report the event definitions or assessment procedures needed to evaluate that possibility.

Enrollment is recorded as 3, and the trial status is terminated. The reason for termination is not reported in the registry record. The record does not describe the dose levels, how ALD518 was administered, how long participants were exposed, or how dose decisions were made. It is therefore not possible to assess dose-specific findings or whether the stated dose-exploration objective was met.

The primary endpoint timeframe is through Week 24, but the registry does not report an analyzed primary result, participant-level follow-up completeness, or handling of missing observations. It also does not report a statistical analysis plan, analysis populations, confidence intervals, or inferential methods. The secondary outcomes are listed, but their results are not reported as analyses.

The adverse-event summary lists counts, percentages for serious-event terms, and deaths, but does not provide timing, event-level details, attribution, or a clear relationship to the primary endpoint. With no control group and limited enrollment, these summaries cannot determine whether observed events were caused by ALD518 or estimate comparative safety. The registry record also does not explain how the summaries were collected or adjudicated.

These limitations are specific to the information and design recorded for this trial. They do not imply that unreported analyses or additional study information do not exist; such information is simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Exploratory Safety Study of ALD518 in Subjects With Steroid-refractory Acute Graft Versus Host Disease (GVHD) — NCT01530256.
• Registry record last updated 2021-02-17; status last verified 2021-02.
• Results first posted 2021-02-17.
• 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 NCT01530256, “Exploratory Safety Study of ALD518 in Subjects With Steroid-refractory Acute Graft Versus Host Disease (GVHD).” It is listed as a Phase 1/2, single-group, unmasked study sponsored by CSL Behring. Enrollment is recorded as 3; the start is 2012-03, primary completion is 2013-03, and status is terminated.

The primary endpoint is the number of participants with adverse events, including infections and loss of engraftment, through Week 24. Listed secondary outcomes concern relapse of underlying malignant disease, overall survival, and FACT-BMT questionnaire score change. The registry lists adverse-event summaries, including serious-event terms and 2 deaths, but no outcome analyses.

The record does not report a primary endpoint analysis, dose-specific findings, the reason for termination, or a comparative treatment effect. Its posted safety summaries are descriptive and should be interpreted in light of the single-group design and enrollment of 3.