An Efficacy and Safety Study of APX001 in Non-Neutropenic Patients With Candidemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of APX001 in Non-Neutropenic Patients With Candidemia (NCT03604705), a na phase 2 study. The primary outcome is Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC).

2. Clinical Question

The study asks whether treatment success is observed at the end of study treatment among non-neutropenic adults with candidemia who receive APX001. The primary endpoint is a participant count, with success defined by the Data Review Committee using a combination of microbiological, survival, and treatment-use criteria. The registry record describes the study as evaluating first-line treatment, including in patients with suspected or confirmed antifungal-resistant candidemia.

These features define a descriptive question about outcomes among treated participants, not a randomized estimate of comparative treatment effect. The record does not report a separate statistical analysis plan or a primary endpoint analysis.

3. Trial Design

This is a phase 2, open-label, single-group study of APX001. The registry describes it as multicenter and non-comparative, with enrollment of 21. Allocation is listed as not applicable, and masking is listed as none. The study was sponsored by Basilea Pharmaceutica. Its status is completed; the registry lists a start date of 2018-10-03 and primary completion date of 2020-03-31.

The target population was non-neutropenic adults 18 years of age and older with candidemia. The study description includes candidemia with or without invasive candidiasis and allows enrollment based on suspected antifungal resistance; documented resistance was not required. The intended treatment context is first-line treatment. The study description says it was to be conducted at approximately 20 sites in the United States and globally.

APX001 treatment could continue for a maximum of 14 days. If further antifungal therapy was indicated to complete treatment of candidemia in accordance with standard practice guidelines, fluconazole could begin after the study drug period for up to a further 7 days, unless susceptibility results warranted alternative antifungal therapy. Follow-up was described as 4 weeks (+4 days) after end of treatment, with total participation of up to approximately 7.5 weeks.

The registry lists treatment success at end of study treatment as the primary outcome, determined by the Data Review Committee. Listed secondary outcomes include time to first negative blood culture; mycological outcomes at end of study treatment, end of treatment, and 2 and 4 weeks after end of treatment; treatment success at end of treatment and at 2 and 4 weeks after end of treatment; overall survival at Study Day 30; and treatment-emergent adverse events. The registry lists 6 outcome measures and 0 analyses. The single-group design is important when interpreting any observed outcome: without a concurrent control, differences attributable to APX001 cannot be isolated from other explanations using this trial alone.

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

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: Treatment Period - MITT

6. Primary Endpoint

The registry lists the primary outcome as Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC), measured over One to forty-two days.

The primary endpoint is treatment success at end of study treatment, reported as a count of participants. The timeframe is listed as one to forty-two days. The Data Review Committee definition requires all of the stated criteria: two consecutive blood cultures negative for Candida spp.; being alive at the end of study treatment; and no concomitant use of any other systemic antifungal therapies through the end of study treatment. A participant who does not meet every criterion does not meet this composite definition.

A composite endpoint combines multiple clinically or scientifically relevant conditions into one outcome. In this study, the culture findings represent microbiological status, survival is an essential condition, and the restriction on concomitant antifungal treatment defines the treatment context under which success is counted. Using these criteria makes the endpoint more specific than a blood-culture result alone, but it also means the count does not identify which component determined a participant's outcome unless component-level results are reported separately.

The registry record identifies the endpoint and its definition but does not report the observed number meeting the definition, the denominator analyzed for this endpoint, or an uncertainty estimate. Therefore, the endpoint's stated purpose can be described, but its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome count represent?

The primary outcome is a count of participants meeting a composite definition at end of study treatment. A count answers how many participants met the criteria in the analyzed group; interpreting it as a rate also requires knowing the relevant denominator. The registry record gives the enrollment and safety population figures, but it does not report the primary outcome count or its endpoint-specific denominator. It is therefore not possible to state the proportion meeting the endpoint from the registry record.

The composite definition requires all of its components. This means that the count is not simply a count of negative blood cultures: participants also had to be alive at end of study treatment and have no concomitant systemic antifungal therapy through that point. If a composite outcome is reported without its component results, it may be difficult to tell which condition most often determined whether the full definition was met. Component-level results are not reported in the registry record.

Why does the single-group design matter?

In a single-group study, outcome measurements describe what happened among participants receiving the study treatment. A concurrent control group can help distinguish treatment effects from other influences, such as the course of illness, participant characteristics, or care received during follow-up. Without such a group, those explanations cannot be separated by a randomized comparison within this study. This is a general limitation of non-comparative designs, not a claim that the observed outcomes are uninformative.

The study was open-label, with masking listed as none. In general, lack of masking can affect outcomes that involve clinical judgment, decisions about additional care, or reporting. The primary endpoint includes culture results and survival as well as a restriction on concomitant systemic antifungal use. The endpoint was determined by the Data Review Committee, but the registry record does not describe how the committee was masked, how disagreements were handled, or what review procedures were used. Those details are not reported in the registry record.

What would an uncertainty interval tell a reader?

In general, a confidence interval communicates the range of values reasonably compatible with an estimate under the statistical model and assumptions used. A narrow interval indicates greater precision than a wide interval, though an interval does not correct design limitations or establish causation. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed. No p-value or inferential analysis for the primary endpoint is reported either.

With a count-based binary outcome, the statistical analysis would need to specify how the count and denominator are used to estimate the frequency of success and how uncertainty is calculated. The registry identifies the endpoint parameter as a participant count, but does not report a statistical method for estimating a rate, handling uncertainty, or testing a hypothesis. These choices must not be inferred from the endpoint label alone.

How should the planning illustrations be understood?

The planning assumptions described for sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such calculations are hypothetical planning illustrations, not observed power and not evidence about the trial's actual treatment effect. The registry record describes this study as single-group, so the two-arm equal-allocation assumptions do not describe its actual design. No sample-size justification for the trial itself is reported in the registry record.

In general, power is a design-stage probability tied to a specified effect, analysis, and assumptions. It is not a measure of the probability that a treatment works after results are observed. Planning estimates based on an observed effect can be particularly dependent on that effect estimate and should not be treated as trial findings. No numerical planning result is reported in the registry record, and no such calculation can substitute for the missing primary endpoint analysis.

Why can event data vary more than a simple model expects?

In general, over-dispersion occurs when observed variation in event counts is greater than a statistical model assumes. If present and ignored, uncertainty estimates can be too small and tests can be poorly calibrated. This concept is most relevant to count models and repeated or clustered event data; it should not be assumed to apply to this study's primary participant-count endpoint. The registry record does not report an over-dispersion assessment or a count-model analysis. It also does not report a method for handling clustering by site.

What does the analysis record establish?

The registry lists 6 outcome measures and 0 analyses. This identifies outcomes recorded in the registry without supplying a corresponding set of analysis results. In particular, the primary endpoint definition is available, but its observed result and statistical uncertainty are not. An analysis plan, model specification, covariate adjustment, interim analysis procedure, and sample-size justification are not reported in the registry record. Without those details and the endpoint results, a reader cannot reproduce or evaluate a formal efficacy analysis from the registry information alone.

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("Treatment Period - MITT")
n      <- c(20)
events <- c(16)
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  Treatment Period - MITT  20  16  80.0  56.3  94.3  58.4  91.9  58.1  91.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including microbiological outcomes, treatment success at later time points, time to first negative blood culture, survival at Study Day 30, and treatment-emergent adverse events. Considering multiple outcomes can increase the chance of finding an apparently notable result by chance if many tests are conducted. In general, a prespecified multiplicity strategy may define which outcomes are primary, how tests are ordered, or how error rates are controlled. No multiplicity strategy is reported in the registry record, and no analyses are listed.

Missing-data methods are also not reported. The registry record does not state how missing blood cultures, incomplete follow-up, early discontinuation, or unavailable endpoint assessments were handled. It does not give the primary endpoint analysis denominator. These omissions matter because a participant-count result can be interpreted differently depending on whether all enrolled participants were included, only those with an evaluable assessment were included, or missing outcomes were handled using another rule. None of those approaches should be assumed.

The registry identifies a safety population of 21, but the primary endpoint population field is not described. The record therefore does not establish that the safety and efficacy populations were identical. No intention-to-treat or per-protocol analysis population is specified in the registry record. Interim analyses, monitoring boundaries, and a statistical analysis plan are also not reported in the registry record. These gaps limit assessment of how outcomes were selected, analyzed, and interpreted, especially given the number of listed outcomes and assessment times.

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: septic shock (9.5%), bacteraemia (4.8%), bacterial sepsis (4.8%), enterobacter sepsis (4.8%), necrotising fasciitis (4.8%).

The safety population is listed as 21. Within that population, the registry reports 9 participants with serious adverse events, 20 with other adverse events, and 5 deaths. The registry also lists serious adverse event terms and percentages: septic shock, 9.5%; bacteraemia, 4.8%; bacterial sepsis, 4.8%; Enterobacter sepsis, 4.8%; necrotising fasciitis, 4.8%; and sepsis, 4.8%.

These are descriptive safety figures. The registry record does not report a comparison group for evaluating whether event frequency differed under another treatment, and it does not establish that the reported events were caused by APX001. The listed terms may describe events that occurred in the same participant, but their overlap is not reported. Therefore, the term percentages should not be added, and the counts for serious events, other events, and deaths should not be treated as mutually exclusive categories. The record does not provide further detail on event timing, severity grading beyond serious-event status, or attribution to study treatment.

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

The registry record establishes that a phase 2, open-label, single-group study of APX001 in non-neutropenic patients with candidemia was completed, and it specifies a primary treatment-success endpoint. The endpoint requires both negative consecutive blood cultures and survival at end of study treatment, as well as no concomitant systemic antifungal therapy through that endpoint. This definition conveys what the study intended to count.

The record does not report the observed primary endpoint count, its denominator, or an estimate with uncertainty. It therefore does not show how often the defined outcome occurred or how precisely it was estimated. The absence of these results should not be interpreted as a positive or negative efficacy finding. Secondary outcomes are listed, but their analyses are not reported in the registry record.

The safety figures describe events recorded in the safety population. They do not by themselves determine whether APX001 caused an event or whether the event frequency differs from what would have occurred under another treatment. The study has no concurrent comparator, and the registry does not report comparative analyses. Thus, the posted information cannot establish a causal treatment effect or support a direct comparison with another therapy.

In general, a well-defined endpoint and a completed study are not equivalent to a reported analysis. Interpretation of efficacy would require the endpoint result, the analysis population, missing-data handling, and an account of uncertainty. Interpretation of comparative effect would additionally require an appropriate comparator and analysis. Those results and details are not reported in the registry record. The conclusions warranted by the posted information are consequently limited to the study design, endpoint definition, and descriptive safety counts.

14. Why This Trial Matters Statistically

This study illustrates a useful statistical distinction between defining an outcome and reporting evidence about that outcome. The primary endpoint is specified in detail, including microbiological, survival, and treatment-use criteria. That definition allows readers to understand what treatment success was intended to mean. But without the observed count, endpoint denominator, and uncertainty estimate, the definition alone cannot establish the frequency or precision of success.

The single-group design also highlights the difference between description and comparison. Outcomes among participants receiving APX001 can be described, but a concurrent control is needed for a randomized within-study comparison. Without one, observed outcomes may reflect factors other than treatment. This is especially important when a study is open-label and when the endpoint includes a criterion related to concomitant treatment.

The registry's multiple listed outcomes make transparent analysis planning important. Prespecification helps readers understand which findings are primary and how multiple tests, missing assessments, and analysis populations were addressed. Those methods are not reported in the registry record. Likewise, the safety counts are informative as descriptions of events in the safety population but do not answer causal or comparative questions.

For biostatisticians and clinical researchers, the record is a reminder to keep endpoint definitions, analysis results, and design-based inference separate. A completed trial record can contain important design and safety information while still lacking the results needed to evaluate a primary efficacy estimate. Accurate interpretation depends on recognizing both what the record documents and what it leaves unreported.

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 most important trial-specific limitation for interpreting efficacy is the non-comparative, single-group design. There is no concurrent control group, so outcomes cannot be attributed to APX001 through a randomized comparison in this study. Open-label conduct may also affect care decisions or outcome assessment; the registry identifies the Data Review Committee but does not describe its procedures or masking.

The registry record does not report the primary endpoint result, an endpoint-specific denominator, or an uncertainty estimate. It also does not report the analysis population for efficacy, missing-data handling, protocol deviations, or the statistical analysis plan. These omissions prevent assessment of the primary outcome's precision and of how participants with incomplete assessments were treated. The record lists 6 outcome measures and 0 analyses, leaving the secondary findings unavailable as well.

The target population is described as non-neutropenic adults with candidemia, including patients with or without invasive candidiasis and suspected resistance. The study enrollment is 21. The registry record does not provide subgroup results or enough information to assess how the findings might apply to particular patient subgroups or settings. It also does not report a sample-size justification for the trial itself. The planning assumptions described for illustrations do not replace that missing justification and do not describe the study's single-group design.

For safety, the record gives participant counts and serious adverse event terms, but does not report attribution, event timing, or the extent of overlap among terms. Without a comparator, these counts cannot establish relative safety. These limitations are specific to the design and registry information available for this study and constrain both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of APX001 in Non-Neutropenic Patients With Candidemia — NCT03604705.
• Registry record last updated 2025-09-16; status last verified 2025-09.
• Results first posted 2021-08-05.
• 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

NCT03604705 is a completed phase 2, open-label, single-group study sponsored by Basilea Pharmaceutica. It evaluated APX001 in non-neutropenic adults with candidemia, including patients with suspected or confirmed antifungal resistance. The registry lists enrollment as 21, a start date of 2018-10-03, and primary completion on 2020-03-31.

The primary outcome was treatment success at end of study treatment, defined by the Data Review Committee using blood culture, survival, and concomitant antifungal therapy criteria. The registry record does not report the primary outcome result or any statistical analyses. It lists 6 outcome measures and 0 analyses. In the safety population, it reports 9 participants with serious adverse events, 20 with other adverse events, and 5 deaths. Because the trial had no concurrent comparator, these safety counts are descriptive and do not establish causation or comparative risk.