This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study) (NCT05238116), a randomized phase 3 study. The primary outcome is Number of Participants Alive With Favorable Overall Response as Assessed by the Data Review Committee (DRC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05238116 |
| Phase | Phase 3 |
| Condition | Refractory IPA |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 85 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pulmocide Ltd |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with refractory invasive pulmonary aspergillosis (IPA). For the interim analysis, the record defines a modified intention-to-treat population as randomized participants with Data Review Committee (DRC)-confirmed refractory, proven or probable IPA who received at least one dose of blinded study drug. The record does not provide a complete description of the population used for a final primary-outcome analysis.
Intervention
Participants assigned to PC945 received it by nebulizer twice daily. The official study title and summary describe nebulized PC945 as an addition to systemic antifungal therapy. Further details about the systemic treatments are not reported in the registry record.
Comparator
The comparator was PC945-placebo, also administered by nebulizer twice daily. The study was placebo-controlled and double-blind according to its official title; the registry describes masking as quadruple. Details of which roles were masked are not reported in the registry record.
Primary question
The primary endpoint asks how many participants were alive and had a complete or partial overall response at Day 84, as assessed by the DRC. The record does not post group-specific results or a statistical comparison for this endpoint. It therefore does not establish from the posted primary-outcome data whether the groups differed, or how precisely any difference was estimated.
3. Trial Design
OPERA-T was a Phase 3, randomized, parallel-group, placebo-controlled study of nebulized PC945 added to systemic antifungal therapy for refractory IPA. The registry lists an enrollment of 85. Participants were assigned to PC945 or placebo; both were administered by nebulizer twice daily. The study title specifies a double-blind design, while the registry's masking classification is quadruple. The record does not explain the roles covered by that classification.
Random allocation is intended to create groups that are comparable, on average, with respect to both measured and unmeasured characteristics. A placebo comparator can help distinguish outcomes associated with the study drug assignment from outcomes that might occur with background care or study participation. Blinding is intended to limit the influence of treatment knowledge on care, assessment, and reporting. These are general design principles; the registry record does not describe how randomization was generated, how assignments were concealed, or how blinding was maintained.
The primary endpoint was a participant count at Day 84: participants alive with a favorable overall response determined by the DRC. The registry also lists secondary outcomes of favorable overall response, time to favorable overall response, and all-cause mortality. It records four outcome measures in total. The outcome-specific analysis procedures and planned comparisons are not reported in the registry record.
The study status is terminated. The record lists no statistical analyses. It does not explain the reason for termination, whether enrollment ended early, or how termination affected data collection or planned analyses. Those details should not be inferred from the status alone. The registry does not report a final analyzed population or the number of participants contributing endpoint data by group.
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
| Stage | PC945 | Placebo |
|---|---|---|
| STARTED | 57 | 28 |
| Received at Least One Dose of Study Drug | 56 | 27 |
| mITT Population | 41 | 20 |
| COMPLETED | 23 | 15 |
| NOT COMPLETED | 34 | 13 |
Reasons for not completing this period:
| Reason | PC945 | Placebo |
|---|---|---|
| Physician Decision | 3 | 0 |
| Withdrawal by Subject | 11 | 2 |
| Study Terminated | 4 | 3 |
| Death | 16 | 7 |
| Participant non-compliance | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: For the interim analysis, the modified intention-to-treat (mITT) population was defined as randomized participants who had DRC-confirmed refractory, proven or probable invasive pulmonary aspergillosis (IPA), and who received at least one dose of blinded study drug. Overall number of participants analyzed = participants evaluable for this outcome measure. Randomization was stratified by mortality risk (high vs low).
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: The Safety Population consisted of all randomized participants who received at least one dose of study therapy.
| Characteristic | Unit | PC945 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 56 | 27 | 83 | |
| Age, Customized: 18 to <64 years | Participants | 39 | 19 | 58 |
| Age, Customized: 65 to <84 years | Participants | 17 | 8 | 25 |
| Age, Customized: ≥85 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 22 | 10 | 32 |
| Sex: Female, Male: Male | Participants | 34 | 17 | 51 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Asian | Participants | 9 | 8 | 17 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 35 | 16 | 51 |
| Race (NIH/OMB): More than one race | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 7 | 3 | 10 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 | 3 | 9 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 41 | 20 | 61 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 9 | 4 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Alive With Favorable Overall Response as Assessed by the Data Review Committee (DRC), measured over At Day 84.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who were alive and had a complete or partial overall response at Day 84. Response was determined by the Data Review Committee (DRC), using the Classification and Criteria for the Assessment of Overall Response, adapted from Segal, 2008. The endpoint combines survival at the assessment time with the response classification: a participant must meet both conditions to be counted as having a favorable overall response.
A participant count is a binary-outcome summary at the individual level: each person either meets the endpoint definition or does not. In general, this kind of endpoint can give a clinically interpretable snapshot at a specified time, while combining two relevant dimensions of outcome. Its meaning depends on the precise response criteria, the assessment process, and how missing or unevaluable assessments are handled. The registry record gives the response definition but does not report rules for missing assessments or the detailed DRC procedures.
The registry names the endpoint and its time point, but does not post the number meeting the endpoint in either group or a comparison between groups. It therefore does not support an estimate of the treatment-group contrast or its precision. The count should not be interpreted as a complete picture of disease course or as a time-to-event result: the endpoint is specifically the number alive with a favorable overall response at Day 84.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized Phase 3 comparison of nebulized PC945 with nebulized placebo, each added to systemic antifungal therapy, in refractory IPA. It defines the primary outcome as the number of participants alive with a complete or partial overall response at Day 84 according to the DRC. However, the posted record does not include group-specific primary-outcome counts, an effect estimate, a confidence interval, or a p-value. No numerical efficacy comparison can therefore be interpreted from the primary endpoint information in the record.
The record lists 85 participants as the enrollment and gives safety counts by assigned group. For PC945, 56 participants were at risk for serious adverse events and 36 were affected; for placebo, 27 were at risk and 18 were affected. The corresponding counts for the separate “other” adverse-event category are 56 at risk and 45 affected for PC945, and 27 at risk and 25 affected for placebo. Deaths are listed as 21 for PC945 and 8 for placebo. These are descriptive counts. They do not, by themselves, establish that an event was caused by study treatment or support a formal comparison adjusted for time at risk or other factors.
The record also lists serious adverse-event terms and percentages: Sepsis, 17.9%; Bronchopulmonary aspergillosis, 11.1%; Septic shock, 11.1%; Pneumonia bacterial, 8.9%; Pyrexia, 7.4%; and Hypernatraemia, 7.4%. The denominator and counting rules for these term-level percentages are not reported in the registry record, so they should be read as listed rather than used to reconstruct group-specific risks.
Interpretation is further limited because the study is marked terminated and the record lists zero analyses. The reason for termination and the extent of outcome follow-up are not reported in the registry record. This means the status cannot be used to infer the direction or size of any treatment effect. The posted information describes the design, endpoint definition, and some safety counts, but does not provide a complete results analysis. Any claim about comparative efficacy, statistical significance, or the precision of an effect would go beyond what is reported.
9. Statistical Methods Explained
Several statistical ideas help clarify what the registry record can and cannot establish. The distinctions below are general explanations; they do not imply that a particular method was used in OPERA-T. The registry lists the trial design and endpoint definition, but its analysis details are not reported in the registry record.
What randomization contributes
In a randomized trial, assignment is determined by a chance-based process rather than by participants' prognosis or clinical features. In general, this helps make groups comparable before treatment begins and supports a causal interpretation of a well-conducted comparison. Randomization does not guarantee that the groups will be identical, particularly in a study with a limited enrollment. It also does not resolve problems caused by incomplete follow-up, deviations from assignment, or analyses that exclude participants selectively.
The registry identifies OPERA-T as randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record. The record also does not state which analysis population was intended for the primary endpoint beyond giving an mITT definition for the interim analysis. That limits assessment of how the randomization was carried into the reported analysis.
How to understand a binary endpoint
The primary outcome is a count of participants who satisfy a two-part condition at Day 84: being alive and having a complete or partial overall response. In general, binary outcomes can be summarized as counts and as proportions, with a comparison expressed on a chosen scale. Common scales include a difference in proportions, a ratio of proportions, or an odds ratio. These scales answer different questions and can convey different impressions, so the planned measure matters.
The registry gives no group-specific primary counts and no effect estimate. No comparison on any of these scales can be recovered from the endpoint definition alone. Even if counts were available, a point estimate would not convey its uncertainty by itself. A confidence interval generally gives a range of values compatible with the data and the model used, while its width reflects statistical precision. Neither an interval nor a p-value for the primary endpoint is reported in the registry record.
Why the assessment process matters
The primary response was assessed by the DRC, and the endpoint uses criteria adapted from a named classification. In general, a committee-based assessment can provide a structured approach, but interpretation still depends on the criteria, available clinical information, adjudication procedures, and handling of disagreements or missing records. The registry does not describe those operational details. It also does not report whether endpoint assessments were complete in each group.
Survival is part of the endpoint definition, rather than a separate condition that can be ignored. A participant who is not alive at Day 84 cannot meet the stated favorable-response definition, regardless of response status at another time. This makes the endpoint a combined status at a fixed assessment time; it is not equivalent to a response-only measure or to a survival analysis across follow-up.
What an analysis population means
The record defines an mITT population for the interim analysis: randomized participants with DRC-confirmed refractory, proven or probable IPA who received at least one dose of blinded study drug. The term identifies a set of participants for analysis, but it does not alone specify how every post-randomization event is treated. Different analysis populations can lead to different estimates if eligibility confirmation, treatment receipt, or outcome availability differs between groups. The final primary analysis population and its handling rules are not reported in the registry record.
In general, an intention-to-treat approach retains participants in their randomized groups, regardless of treatment received, to preserve the comparison created by randomization. A modified intention-to-treat approach applies some additional inclusion condition. The record's interim definition includes randomization, confirmed disease, and receipt of at least one dose. It should not be assumed that this was the final analysis set or that its use was prespecified for the final endpoint.
Multiplicity, missingness, and safety summaries
When a study evaluates several endpoints or makes several comparisons, the chance of at least one false-positive finding can rise if each is tested without adjustment. Statistical plans sometimes address this through a testing hierarchy or an adjustment to inference. The registry lists secondary outcomes, but the multiplicity approach is not reported in the registry record. It also does not provide missing-data rules, imputation methods, or sensitivity analyses. These are important because incomplete outcome data can affect both the estimate and its uncertainty.
For safety, counts of participants with events describe how many people were affected, while event counts can describe repeated occurrences. These are not interchangeable summaries. A time-to-event or exposure-adjusted analysis may be needed when follow-up duration differs, but no such analysis is reported in the registry record. The posted at-risk and affected counts should therefore be read as descriptive, not as a complete inferential comparison.
Planning illustrations are not trial results
In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. The record describes planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also specifies that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations use total events. Such illustrations are not the trial's original design justification, do not show that a study had adequate power, and are not observed power. The registry does not report the trial's own sample-size justification. Since the primary comparison is not posted, these planning assumptions cannot substitute for an observed treatment-effect estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and secondary outcomes that include favorable overall response, time to favorable overall response, and all-cause mortality. It records four outcome measures. Evaluating multiple outcomes can create multiplicity: if each is tested separately, the overall chance of at least one false-positive result may be greater than the nominal error rate for an individual test. General approaches include prespecifying a hierarchy, adjusting significance thresholds, or treating secondary findings as exploratory. The approach used in OPERA-T is not reported in the registry record.
The record does not report a statistical analysis plan, the planned effect measure for the primary endpoint, or whether interim analyses were planned or conducted. The endpoint population description refers to an interim analysis, but that alone does not establish the existence, timing, or conduct of any interim analysis. The registry lists zero analyses, and no final primary-outcome comparison is posted.
Missing-data handling is also not reported in the registry record. There is no description of how participants without a Day 84 assessment, participants who withdrew, or participants with unevaluable response would be classified or included. The interim mITT population definition is available, but the final analysis population is not reported in the registry record. Without these details, it is not possible to assess whether incomplete follow-up could have affected the endpoint comparison or how robust any result would be to alternative assumptions.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| PC945 | 36 | 56 | 64.3% |
| Placebo | 18 | 27 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PC945 | 21 of 57 |
| Placebo | 8 of 28 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PC945 | 45 of 56 |
| Placebo | 25 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | PC945 | Placebo |
|---|---|---|---|
| Sepsis | Infections and infestations | 10 of 56 | 1 of 27 |
| Bronchopulmonary aspergillosis | Infections and infestations | 6 of 56 | 3 of 27 |
| Pneumonia bacterial | Infections and infestations | 5 of 56 | 2 of 27 |
| Septic shock | Infections and infestations | 3 of 56 | 3 of 27 |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 4 of 56 | 1 of 27 |
| Pneumonia | Infections and infestations | 3 of 56 | 1 of 27 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 4 of 56 | 0 of 27 |
| Febrile neutropenia | Blood and lymphatic system disorders | 2 of 56 | 1 of 27 |
| Blood bilirubin increased | Investigations | 2 of 56 | 1 of 27 |
| Delirium | Psychiatric disorders | 1 of 56 | 2 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PC945 | Placebo |
|---|---|---|---|
| Pyrexia | General disorders | 7 of 56 | 4 of 27 |
| Cough | Respiratory, thoracic and mediastinal disorders | 6 of 56 | 4 of 27 |
| Diarrhoea | Gastrointestinal disorders | 4 of 56 | 5 of 27 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 4 of 56 | 4 of 27 |
| Abdominal pain | Gastrointestinal disorders | 6 of 56 | 1 of 27 |
| Headache | Nervous system disorders | 5 of 56 | 2 of 27 |
| Nausea | Gastrointestinal disorders | 4 of 56 | 2 of 27 |
| Hyperkalaemia | Metabolism and nutrition disorders | 3 of 56 | 3 of 27 |
| Hypokalaemia | Metabolism and nutrition disorders | 2 of 56 | 4 of 27 |
| Bacteraemia | Infections and infestations | 4 of 56 | 1 of 27 |
Serious events with the highest arm-level rate: sepsis (17.9%), bronchopulmonary aspergillosis (11.1%), septic shock (11.1%), pneumonia bacterial (8.9%), pyrexia (7.4%).
The registry lists serious adverse-event counts separately for the PC945 and placebo groups. In the PC945 group, 56 participants were at risk and 36 were affected; in the placebo group, 27 were at risk and 18 were affected. These counts describe participants, not necessarily the total number of separate serious events. The record also gives deaths as 21 for PC945 and 8 for placebo. It does not state in this summary whether deaths were attributed to treatment, arose during a particular interval, or were included among participants with serious adverse events.
A separate “other” adverse-event category lists 56 at risk and 45 affected in the PC945 group, and 27 at risk and 25 affected in the placebo group. The definition of this category is not reported in the registry record. The term-level serious adverse-event list gives Sepsis, 17.9%; Bronchopulmonary aspergillosis, 11.1%; Septic shock, 11.1%; Pneumonia bacterial, 8.9%; Pyrexia, 7.4%; and Hypernatraemia, 7.4%. The record does not specify the denominator for those percentages in the posted information.
These summaries are descriptive and should not be treated as causal estimates. They do not adjust for follow-up duration, repeated events, baseline differences, or other factors. The record does not report a statistical comparison of safety outcomes or an assessment of attribution. Counts alone therefore do not establish whether the groups differed in risk.
12. What the Result Does, and Does Not, Mean
The posted information establishes that OPERA-T was designed as a randomized, parallel-group, placebo-controlled Phase 3 study of nebulized PC945 added to systemic antifungal therapy for refractory IPA. It also specifies the primary endpoint, its Day 84 assessment time, and the response definition used by the DRC. The registry reports safety counts for the two groups and lists several serious adverse-event terms.
Those design and descriptive details are not equivalent to a comparative efficacy result. The registry does not report the number of participants in each group who were alive with a favorable overall response at Day 84. Nor does it report an estimated group contrast, confidence interval, or p-value. The available record therefore does not show the magnitude or precision of a primary-outcome difference. It cannot support a conclusion about whether PC945 changed the chance of meeting the endpoint relative to placebo.
The safety counts have a similarly limited interpretation. They indicate how many participants are listed as at risk and affected in the serious and separate other adverse-event categories, and how many deaths are listed. They do not by themselves identify causes, establish treatment attribution, or account for differences in exposure or follow-up. No comparative safety analysis is reported in the registry record.
The terminated status is important context, but it does not explain why the study ended or what data were collected. The reason for termination, completeness of follow-up, and any effect on the planned analysis are not reported in the registry record. A terminated study may have results, but status alone cannot reveal what those results were. Here, the registry lists no analyses, so efficacy and inferential safety findings cannot be reconstructed from the posted summaries.
In short, the record documents a trial question and some event counts, not a complete results assessment. It does not establish that the intervention was effective or ineffective, and it does not establish that the groups had equivalent outcomes. Those conclusions require comparative outcome results and an account of their analysis that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial matters statistically because its primary outcome combines survival with a response classification at a fixed time. That construction makes the endpoint more specific than response alone: participants must be alive and meet the complete-or-partial response definition at Day 84. It also means that the endpoint should be interpreted as a combined status at that assessment, rather than as a measure of response over the entire course of illness or as a survival-time analysis.
The study's design also illustrates the role of randomization, placebo control, and masking in a clinical comparison. In general, these features are intended to reduce bias and strengthen the interpretation of differences between assigned groups. Their value depends on how allocation, masking, follow-up, and analysis were implemented. The registry record identifies the design classifications, but does not describe those procedures in detail.
Equally important is the difference between a trial being registered and a complete results analysis being available. The record gives the endpoint definition and safety summaries, but not a numerical primary comparison or inferential analysis. Without counts by group for the primary endpoint, readers cannot assess the estimated effect or its uncertainty. This is a useful reminder that endpoint definitions, enrollment information, and safety listings do not replace comparative results.
The record's terminated status and its absence of listed analyses make transparent reporting particularly relevant. The reason for termination and the completeness of the data are not reported in the registry record. No conclusion should be drawn about the cause or consequences of termination from the status label alone. Statistically, the most defensible reading is to distinguish the documented design and descriptive counts from the unreported efficacy estimate, uncertainty, and analysis decisions.
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 primary limitation is the absence of group-specific results for the Day 84 primary endpoint. No effect estimate, confidence interval, or p-value is reported in the registry record. Because the endpoint is not reduced to a single comparison in the posted information, the primary treatment contrast cannot be evaluated from the registry summary.
The record provides an interim mITT population definition but does not identify the final primary analysis population. It does not report how missing or unevaluable Day 84 assessments were handled, whether participants were analyzed according to randomized assignment, or how deviations from treatment were addressed. The detailed DRC procedures and endpoint-adjudication process are also not reported in the registry record.
Although the study is marked terminated, the reason for termination and its implications for recruitment, follow-up, and analysis are not reported in the registry record. The record lists enrollment of 85, but does not provide group-specific disposition, outcome availability, or the number included in each analysis. This prevents assessment of whether the posted safety counts cover the same participants as the endpoint population.
The safety summaries are limited to counts, a separate “other” category, deaths, and listed serious-event terms with percentages. Definitions for the other category and denominators for the term percentages are not reported in the registry record. No exposure-adjusted or inferential safety analysis is posted. The registry also does not report the trial's sample-size justification, a full statistical analysis plan, or the approach to multiplicity. These omissions restrict assessment of precision, bias, and robustness; they do not establish that any particular problem occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study) — NCT05238116.
- Registry record last updated 2026-04-30; status last verified 2026-01.
- Results first posted 2026-04-30.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
OPERA-T (NCT05238116) is registered as a Phase 3 randomized, quadruple-masked, parallel study of nebulized PC945 versus nebulized placebo, both added to systemic antifungal therapy for refractory IPA. The record lists an enrollment of 85 and a terminated status.
The primary endpoint is the number of participants alive with a complete or partial overall response at Day 84, assessed by the DRC. The registry does not report group-specific primary counts or a statistical comparison. It lists serious adverse-event, other adverse-event, and death counts for both groups, as well as selected serious-event terms. The record lists four outcome measures and zero analyses. The reason for termination, final analysis population, missing-data procedures, and statistical analysis plan are not reported in the registry record.