Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds (NCT04240886), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42.

2. Clinical Question

The study focused on invasive mold infections due to Aspergillus or rare molds, with the brief description naming Scedosporium, Fusarium, and Mucorales fungi as examples. The stated primary outcome captures mortality during the specified period after treatment began. Secondary outcomes covered global response assessed by the DRC at the end of study drug treatment, treatment success or failure, adverse events, clinical abnormalities, and plasma concentrations of fosmanogepix. These outcomes address different aspects of response, safety, and drug exposure; they are not interchangeable measures of the primary mortality outcome.

3. Trial Design

The registry describes NCT04240886 as a Phase 2, multicenter, open-label, non-randomized, parallel study sponsored by Basilea Pharmaceutica. Its title describes APX001 for patients with invasive mold infections caused by Aspergillus species or rare molds. The intervention is also named fosmanogepix. The listed enrollment is 21. The record identifies Cohort A and Cohort B, with both descriptions naming fosmanogepix, but gives no further cohort-specific treatment details in those descriptions.

The study started on 2020-01-04, had a primary completion date of 2022-03-29, and is listed as terminated. The reason for termination is not reported in the registry record. The record does not give the number enrolled in each cohort, nor does it establish a randomized treatment allocation. Although the design is described as parallel, that label does not make the cohorts comparable in the way randomized treatment groups would be.

Open-label means the study is not described as masking treatment assignment. In general, lack of masking can influence expectations, treatment decisions, reporting, and assessments, particularly for outcomes that require judgment. The primary outcome of death is less dependent on subjective rating than a response assessment, but interpretation still depends on the completeness and consistency of outcome ascertainment. The registry record does not describe additional procedures for reducing assessment bias.

The trial is not a randomized comparison, and both named cohorts received the same intervention according to their short descriptions. Therefore, a contrast between cohorts should not be interpreted as an estimate of the causal effect of fosmanogepix versus another treatment. Cohort-specific characteristics, allocation rationale, and the statistical plan are not reported in the registry record. The record also does not report why the study was terminated or whether termination affected planned follow-up.

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.

Treatment Phase

Reasons for not completing this period:

Follow-up Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified Intent-to-Treat (mITT) population included all participants who entered in the study, received at least 1 dose of study drug, and had a diagnosis of proven or probable IMI confirmed by the DRC.

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: Safety population included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42, measured over After first dose on Day 1 through Day 42.

The primary endpoint is the percentage of participants who died after their first dose of study drug through Day 42. Its description states that deaths from Day 1 through Day 42 were included. The population specified for this outcome is the modified Intent-to-Treat population: participants who entered the study, received at least 1 dose, and had proven or probable invasive mold infection confirmed by the DRC.

Mortality is a direct, clinically meaningful outcome and can be summarized as the proportion of a defined population experiencing death during a specified period. As a general statistical point, a fixed-window percentage is easier to interpret when the population, starting point, follow-up window, and handling of incomplete follow-up are clear. The registry record defines the population and time window, but does not report how incomplete follow-up or missing outcome status was handled.

The endpoint is listed with an 80% Confidence Interval. A confidence interval communicates uncertainty around an estimate; it does not make the estimate a prediction for an individual participant. The registry record does not provide the observed mortality percentage or its interval, so the magnitude and precision of the primary outcome cannot be assessed from this record. The adverse-event listing includes a death count, but it does not establish that this count refers to deaths within the primary endpoint’s Day 1-through-Day 42 window. Those figures should not be substituted for the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

The primary outcome is a binary event summarized as a percentage: a participant either meets the outcome definition during the specified follow-up period or does not. For this study, the event is death after the first dose through Day 42. In general, a percentage communicates how common an event was in a defined group over a defined period. It should be interpreted alongside the group definition and follow-up window, rather than as a rate per unit of time.

The stated mITT population is restricted to people who entered the study, received at least 1 dose, and had proven or probable invasive mold infection confirmed by the DRC. This definition identifies who is intended to contribute to the primary analysis, but the registry record does not report the actual number included in that analysis or how missing outcome information was handled. Enrollment and analysis-population size are not necessarily interchangeable concepts.

What does the confidence interval add?

The primary endpoint is specified with an 80% Confidence Interval. In general, a confidence interval expresses the uncertainty associated with an estimated quantity under a statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. The interval does not remove possible bias from missing data, outcome classification, or study design. Because the registry record does not report the estimated percentage or the interval bounds, its precision cannot be evaluated.

An 80% confidence interval is the level recorded for this endpoint. The registry does not report why this level was selected, whether other interval levels were planned, or how the interval was calculated. It would be speculation to infer a statistical rationale or an analysis procedure beyond the recorded information.

Why does the design matter for interpretation?

Random allocation is a method used in general to balance measured and unmeasured characteristics across treatment groups, on average. This study is explicitly listed as non-randomized. The two cohorts are both described as receiving fosmanogepix, and the record does not identify a separate control intervention. Thus, the record does not support a randomized treatment contrast. In general, comparisons between non-randomized groups may be affected by differences in who entered each group and by other factors that were not measured or adjusted for. The record does not report cohort-specific baseline characteristics or an adjustment strategy.

The study is open-label, meaning masking is listed as none. In general, awareness of treatment can affect care decisions and assessment, particularly when outcomes involve clinical judgment. The primary endpoint is death, whereas secondary global-response assessments involve a DRC. The record names the DRC but does not describe its procedures, masking, or adjudication rules. The extent to which assessment was protected from bias is therefore not reported in the registry record.

What does the sample-size illustration mean?

The stated sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event calculations, the stated output is total events; for other calculations, it is participants per arm. These are planning assumptions, not a description of the study’s actual allocation or proof that the study had a particular power.

In general, power is a design-stage probability calculated under specified assumptions; it is not a measure of how persuasive an observed result is. A sample-size calculation based on an observed effect is a planning illustration and should not be described as observed power. Equal allocation between two arms is an assumption in that illustration, while this registry record describes a non-randomized study with two cohorts both named for fosmanogepix. The assumptions therefore do not establish that the actual trial used equal allocation or had a control arm. No sample-size justification or statistical plan is reported in the registry record, and no calculated sample-size values are included in the registry record for this analysis.

How should multiple outcomes be considered?

The registry lists nine outcome measures. They cover mortality, global response, treatment success or failure, adverse events, clinical abnormalities, and plasma concentrations. In general, assessing many outcomes raises a multiplicity question: the more statistical tests conducted, the greater the chance that at least one result may appear noteworthy by chance if each is interpreted without adjustment. The registry record does not report whether multiplicity was addressed, which outcomes were included in any inferential analysis, or whether a hierarchy was prespecified. It lists zero analyses, so no multiplicity-adjusted or unadjusted test results are available for interpretation.

For binary outcomes, it is important to know the number of participants eligible for each measure, the number with the event, and the rule used for missing observations. For safety outcomes, a participant can experience several event types, so term-specific counts need not represent distinct people. These are general considerations; the registry record does not provide the event-level data, missing-data rules, or analysis details needed to assess them fully.

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("APX001 (Fosmanogepix): Cohort A")
n      <- c(20)
events <- c(5)
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  APX001 (Fosmanogepix): Cohort A  20  5  25.0  8.7  49.1  11.2  46.9  11.3  47.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures, identifying death through Day 42 as the primary outcome and listing global response, treatment success or failure, adverse events, clinical abnormalities, and plasma concentrations among the secondary outcomes. It reports zero analyses. No statistical analysis plan, testing hierarchy, or multiplicity adjustment is reported in the registry record. Therefore, there is no basis for determining whether any family of secondary-outcome tests was planned or how multiple comparisons would have been handled.

The primary analysis population is defined as the mITT population: participants who entered the study, received at least 1 dose, and had proven or probable invasive mold infection confirmed by the DRC. This definition does not specify how missing Day 42 status, withdrawal, or incomplete follow-up was treated. Missing-data methods, censoring rules, and sensitivity analyses are not reported in the registry record. Without these details, the effect of incomplete outcome ascertainment on the endpoint cannot be evaluated.

The listed enrollment is 21, but the analysis population size and cohort-specific enrollment are not reported. The safety listing gives its own at-risk counts, which should not automatically be assumed to define the denominator for the primary outcome or every secondary outcome. The record also does not report whether participants could contribute to multiple serious-event terms or how repeated events were counted.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (14.3%), cardiac arrest (9.5%), diarrhoea (9.5%), sepsis (9.5%), respiratory failure (9.5%).

The safety listing for APX001 (fosmanogepix), Cohort A, records 21 participants at risk for the serious adverse-event measure and 13 participants affected. Its separate other adverse-event category records 21 at risk and 21 affected. The listing also records 9 deaths. These figures describe the entries in the registry’s safety information; they do not by themselves establish that study drug caused an event. The record does not provide enough detail to interpret the other-event category more specifically.

The listed serious-event terms are febrile neutropenia at 14.3%, cardiac arrest at 9.5%, diarrhoea at 9.5%, sepsis at 9.5%, respiratory failure at 9.5%, and thrombocytopenia at 4.8%. These are term-specific percentages. In general, participants may experience more than one event type, so term percentages should not be added or treated as mutually exclusive. The registry record does not provide event-level timing or detail on overlap.

The 9 deaths in the safety listing should not be assumed to equal deaths in the primary endpoint window. That endpoint covers Day 1 through Day 42 after the first dose, while the safety entry does not specify the same time window. The primary mortality percentage and its 80% confidence interval are not reported in the registry record.

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

The registry record establishes that a Phase 2, open-label, non-randomized study evaluated fosmanogepix in invasive mold infections and defined a primary endpoint based on death through Day 42. It also provides a safety listing for Cohort A, including serious adverse-event counts, term-specific percentages, and a death count. These are descriptive features of the registered study and its posted safety information.

The primary endpoint result is not reported in the registry record. Without the observed percentage and confidence interval, the mortality outcome’s magnitude and precision cannot be assessed. The safety listing’s death count does not fill that gap because the record does not establish that it uses the same population and time window. The registry also does not report results for its listed response and other secondary outcomes in the registry record for this analysis.

The study’s non-randomized design and lack of a separately described comparator prevent a like-for-like controlled treatment-effect interpretation. A treatment outcome observed in a single-arm setting or in cohorts without randomized allocation cannot, on its own, show what would have happened under another treatment. General comparisons may be influenced by underlying differences between participants and other factors. The registry record does not provide information needed to adjust for such differences.

Likewise, the listed adverse events should not be interpreted as proof of causation. Safety events can occur in the setting of serious illness and treatment; the record does not establish attribution for the listed terms. The study status is terminated, but the reason for termination is not reported in the registry record. No conclusion about the reason, the effect on follow-up, or treatment efficacy should be inferred from that status alone.

14. Why This Trial Matters Statistically

This trial is statistically notable because it defines a focused mortality outcome while leaving the outcome estimate unreported in the registry information available for analysis. The endpoint specifies a population, starting point, and follow-up window, which are essential elements for interpreting a binary outcome. Yet without the percentage and its 80% confidence interval, neither the observed level nor the precision can be discussed.

The distinction between outcome definition and outcome result matters in registry interpretation. A clearly worded endpoint does not supply evidence about its observed value. Likewise, the presence of multiple secondary outcomes does not establish that they were analyzed or that results favored a particular interpretation. The record lists nine outcomes but zero analyses.

The non-randomized design also matters. The study has two named cohorts, both described as receiving fosmanogepix, and no separate control treatment is identified. A parallel structure alone does not create a randomized comparison. Any group contrast would need careful attention to how participants entered cohorts and how their characteristics differed; those details and any adjustment plan are not reported in the registry record.

Finally, safety counts and the primary mortality endpoint are different kinds of information. The adverse-event listing identifies serious-event counts and specific terms, but it does not specify that its death count falls within the primary endpoint’s time window. Keeping these summaries separate prevents an adverse-event entry from being mistaken for a primary-outcome result. This record therefore illustrates why study design, outcome definitions, denominators, timing, and actual results must be read together before drawing statistical conclusions.

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 limitation for interpreting the main outcome is that its observed percentage and 80% confidence interval are not reported in the registry record. The safety listing includes a death count, but its time window and relationship to the primary endpoint population are not specified. It cannot be used to reconstruct the primary result.

The record describes a non-randomized design, with Cohort A and Cohort B both named for fosmanogepix, but does not report cohort-specific enrollment or further treatment details. It does not identify a separate comparator group. This limits treatment-effect interpretation and precludes treating the cohorts as randomized, like-for-like controls.

Other design and analysis details are also absent. The reason for termination, eligibility criteria beyond the stated mITT definition, baseline characteristics, missing-data handling, cohort allocation rationale, and statistical analysis plan are not reported in the registry record. The record does not explain whether the DRC was masked or provide its assessment procedures. It also does not report outcome results for the listed secondary measures.

The safety listing gives counts and term-specific percentages but does not provide participant-level event detail, timing, overlap between terms, or attribution information. Consequently, the entries are descriptive and cannot establish causation or explain the full clinical context of each event. These limitations apply to interpretation of the registry record and do not establish why the study ended or what its unreported outcomes were.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds — NCT04240886.
• Registry record last updated 2025-09-16; status last verified 2025-08.
• Results first posted 2023-05-19.
• 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

NCT04240886 is listed as a Phase 2, multicenter, open-label, non-randomized, parallel study sponsored by Basilea Pharmaceutica. It evaluated fosmanogepix, also called APX001, in invasive mold infections caused by Aspergillus species or rare molds. Listed enrollment is 21. The study started on 2020-01-04, had primary completion on 2022-03-29, and is listed as terminated.

The primary endpoint was the percentage of participants who died after the first dose through Day 42, in a defined mITT population, with an 80% confidence interval specified. Its result is not reported in the registry record. The safety listing for Cohort A records 13 participants with serious adverse events among 21 at risk, and 9 deaths, but does not establish that the death count matches the primary endpoint window. The registry lists nine outcome measures and zero analyses. The reason for termination and the statistical analysis plan are not reported in the registry record.