BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants With Inadequate Response to C5 Inhibitor Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants With Inadequate Response to C5 Inhibitor Therapy (NCT05116774), a randomized phase 2 study. The primary outcome is Part 1: Change From Baseline in Hemoglobin at Week 24.

2. Clinical Question

The study was intended to evaluate efficacy, safety, and tolerability of BCX9930 monotherapy compared with continued C5-inhibitor therapy. Its clinical question is specific to participants described as having inadequate response and residual anemia while receiving a C5 inhibitor. It does not, from the registry information available, address people with PNH outside that description or make a comparison across all possible treatment choices.

The randomized allocation gives the study a comparative structure, while the open-label design means masking was absent. The primary endpoint is a change in a laboratory measure over time, not a direct report of how participants felt or functioned. Other listed outcomes included transfusion-related measures, fatigue, lactate dehydrogenase, hemoglobin thresholds and stabilization, and C3-opsonized red blood cells. Numerical results for those secondary outcomes are not reported in the registry record.

3. Trial Design

This was a randomized, open-label, multicenter, parallel-group Phase 2 study. The registry lists enrollment of 12 participants and a status of terminated. It describes the study as evaluating oral BCX9930 monotherapy against continued C5-inhibitor therapy in adults with PNH and residual anemia despite C5-inhibitor treatment. The registry record does not report the allocation ratio or the number assigned to each group.

During Part 1, participants in the BCX9930/BCX9930 group received BCX9930, while participants in the C5-inhibitor group continued their existing C5-inhibitor therapy. The record names eculizumab and ravulizumab among the drug interventions. The primary endpoint was change from baseline in hemoglobin at Week 24. The analysis population is described as Part 1 ASaT participants with available data.

The BCX9930/BCX9930 group description says that participants continued BCX9930 during Part 2. It also describes a protocol amendment under which participants who had previously received 500 mg twice daily and remained on treatment had their dose adjusted to 400 mg twice daily. The description of dosing for newly enrolled participants is incomplete in the registry record, so the complete dosing plan cannot be reconstructed from that description.

The sponsor decided to halt enrollment permanently and terminate the study. The registry describes participants in the C5-inhibitor group entering Part 2 after that decision and switching to open-label BCX9930 monotherapy before Week 24, if earlier. This transition means Part 2 did not simply preserve the original continued-C5-inhibitor comparison. The reason for termination beyond the sponsor’s decision to halt enrollment is not reported in the registry record. Details of recruitment, the allocation procedure, and the planned duration of follow-up beyond the stated endpoint timeframe are not reported in the registry record.

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 study was conducted in France, Hungary, Italy, Spain and United Kingdom.

Part 1 (up to 24 Weeks)

Reasons for not completing this period:

Part 2 (up to 52 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the all subjects as treated (ASaT) population in Part 1 with available data were analyzed.

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 included all participants who received at least 1 dose of study drug, whether C5 inhibitor or BCX9930.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Change From Baseline in Hemoglobin at Week 24, measured over Baseline, Week 24.

The primary endpoint was change from baseline in hemoglobin at Week 24, measured in grams per deciliter (g/dL). It is a continuous outcome, and the registry identifies the summary measure as a mean with standard deviation. A change endpoint compares a participant’s measurement at follow-up with that participant’s baseline measurement, then summarizes those changes for the analysis population. It is intended to represent how hemoglobin levels changed over the stated study period.

Hemoglobin is used in this study as a laboratory measure relevant to the residual anemia described in the trial population. A continuous measure can retain information across its observed range rather than reducing the outcome to whether each participant did or did not cross a threshold. The registry also lists secondary outcomes involving hemoglobin thresholds and stabilization, but those are distinct from the primary change-from-baseline measure.

The listed population was Part 1 ASaT participants with available data. The record does not report the number with endpoint data, group-level baseline or Week 24 means, mean changes, a between-group estimate, a confidence interval, or a test result. Consequently, the endpoint definition is available, but its numerical findings and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, open-label, multicenter, parallel-group Phase 2 study. Randomization is a design approach intended to make assigned groups comparable, on average, with respect to measured and unmeasured factors. It does not guarantee balance in any particular trial, especially when enrollment is limited. The record does not report the allocation ratio, the randomization procedure, or group sizes for the primary analysis. Open-label means masking was absent; the registry lists masking as none. In general, awareness of assigned treatment can influence participant reporting, care decisions, and outcome assessment, although the primary endpoint is a laboratory measurement.

What does a mean change represent?

The primary endpoint is change from baseline in hemoglobin at Week 24, summarized as a mean with standard deviation. In general, a mean change describes the average of individual changes in the analyzed group. The standard deviation describes how spread out individual measurements or changes are around that mean; it is not itself a measure of uncertainty in the group mean. Uncertainty in an estimated mean or between-group contrast is usually communicated with a confidence interval or another inferential measure. Those numerical summaries are not reported in the registry record.

A comparison of mean changes between randomized groups can estimate the average difference in change, subject to the analysis population, missing data, and modeling choices. The record does not report a numerical between-group estimate or identify the statistical model used for the primary analysis. It therefore cannot support a reconstruction of that comparison. A change-from-baseline endpoint also depends on how baseline and follow-up measurements are defined and handled; details beyond the stated baseline and Week 24 timeframe are not reported in the registry record.

How should confidence intervals and p-values be understood?

As a general statistical concept, a confidence interval conveys the range of effect estimates compatible with the data and the method used, with wider intervals indicating less precision. A p-value assesses how unusual the data would be under a specified null model and its assumptions; it does not measure the probability that a treatment is effective. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. The absence of those values means statistical significance and precision cannot be assessed from this record.

The record lists 16 outcome measures and 0 analysis entries. It also indicates that the primary outcome was not reduced to a single comparison because it has several categories or time points. These details do not establish which comparisons were prespecified, which were tested, or how the analysis handled multiple outcomes. The statistical analysis plan, including model specification, covariate adjustment, handling of repeated measurements, and any multiplicity procedure, is not reported in the registry record.

What do the planning assumptions mean?

The planning illustration is described as being computed from the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. In general, such an illustration estimates the sample size needed under the stated assumptions; it is not a result about the number of participants actually enrolled or analyzed. The listed values are planning illustrations, not observed power. The registry record does not report the trial’s own sample-size justification, whether the study was planned around this illustration, or the assumptions used in its original design.

A normal approximation is a simplifying method for translating an assumed effect and variability into a planning estimate. Equal allocation is an assumption for the illustration, not evidence that the study enrolled or analyzed equal numbers in each group. Because the record does not report the numerical observed effect used in the illustration or the variability assumptions, the planning calculation cannot be independently evaluated from the registry information. No additional sample-size result should be inferred from the stated assumptions alone.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means the observed variability is greater than a model expects under a basic count distribution. If a model ignores that extra variability, its standard errors can be too small and its intervals too narrow. This is a general consideration for count outcomes such as transfusion-unit measures; the registry’s secondary outcomes include the number of pRBC units transfused. The statistical model for that outcome, any assessment of over-dispersion, and any adjustment are not reported in the registry record. This concept does not change the definition of the primary continuous hemoglobin endpoint.

Likewise, general interpretation of adverse-event counts requires attention to the number of participants at risk, duration of observation, and whether events are counted per participant or as repeated events. The registry provides group-level at-risk and affected counts, but does not report exposure-adjusted rates or enough detail to infer event timing. Those counts are descriptive and should not be read as formal treatment comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including the primary hemoglobin endpoint and secondary outcomes covering transfusion, fatigue, lactate dehydrogenase, hemoglobin thresholds and stabilization, and C3-opsonized red blood cells. When a study evaluates multiple outcomes or time points, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches to this issue include prespecifying a primary comparison or adjusting inference across a family of tests. The multiplicity strategy, if any, is not reported in the registry record. The record also does not identify which secondary outcomes were formally tested or how results across time points were handled.

The primary analysis population is described as Part 1 ASaT participants with available data. This indicates that the endpoint analysis was limited to participants with available measurements, but it does not explain how missing measurements were handled. The number of participants with available Week 24 data, reasons for missingness, imputation methods, sensitivity analyses, and treatment of participants who discontinued are not reported in the registry record. In general, missing-data methods matter because results can be affected when the likelihood of a measurement being missing is related to participant characteristics or outcomes.

The record does not state whether the analysis followed randomized assignment regardless of treatment received, or whether it used another analysis strategy beyond naming the ASaT population. It also does not report a protocol-defined analysis population or a statistical analysis plan. With no analysis entries and no numerical primary results, the impact of multiplicity and missing data on the reported treatment comparison cannot be evaluated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: rash erythematous (33.3%), blood creatinine increased (12.5%), acute kidney injury (12.5%).

The registry reports serious adverse event counts for BCX9930/BCX9930, C5-INH, and BCX9930 After C5-INH. The serious-event summaries list 2 affected among 8 at risk for BCX9930/BCX9930, 0 among 4 for C5-INH, and 1 among 3 for BCX9930 After C5-INH. The listed deaths are 0 in each group. These are counts as recorded, not adjusted comparisons of safety between treatments.

For other adverse events, the record lists 7 affected among 8 at risk for BCX9930/BCX9930, 3 among 4 for C5-INH, and 3 among 3 for BCX9930 After C5-INH. The registry also lists the serious adverse event terms Rash erythematous at 33.3%, Blood creatinine increased at 12.5%, and Acute kidney injury at 12.5%. The record does not provide enough context to assign those term percentages to a particular group or to interpret their denominator.

Small group counts can change substantially with each participant, and the groups may differ in treatment exposure and observation time. The registry does not report exposure-adjusted rates, event timing, or a causal assessment. These figures describe recorded events; they do not establish that a treatment caused an event or permit a reliable comparative safety conclusion.

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

The registry record establishes that this was a randomized, open-label Phase 2 study intended to compare oral BCX9930 monotherapy with continued C5-inhibitor treatment in adults with PNH and residual anemia despite C5-inhibitor therapy. It defines a primary endpoint—change from baseline in hemoglobin at Week 24—and names the analysis population as Part 1 ASaT participants with available data. These details clarify the clinical question and the type of outcome the study was designed to assess.

The record does not report numerical results for the primary endpoint or analysis entries. It therefore does not establish the size or direction of a hemoglobin change, the difference between groups, or the precision of such an estimate. It also does not provide statistical evidence from which to determine whether a difference is compatible with chance under a specified model. A study’s objective and endpoint definition are not evidence that the intended effect was observed.

The study’s termination and enrollment of 12 describe the conduct of the trial, not its clinical result. The sponsor decided to halt enrollment permanently and terminate the study, and the record describes a switch to open-label BCX9930 for the C5-inhibitor group in Part 2 before Week 24, if earlier. The registry does not report a fuller explanation for the termination or enough endpoint-analysis information to determine how treatment transitions affected the results.

The adverse-event counts provide descriptive safety information, but they do not establish causation or a comparative safety profile. The registry also lacks details needed to assess missing data, multiplicity, and the planned statistical analysis. Consequently, the posted information can describe the trial’s design, endpoint, termination, and recorded safety counts, but it cannot support a conclusion about whether BCX9930 changed hemoglobin or how its overall benefit and risk compared with continued C5-inhibitor therapy.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated clinical question and a defined endpoint are only part of the evidence needed to interpret a randomized trial. The registry identifies the target population, the Part 1 treatment comparison, and a continuous primary outcome at Week 24. Yet without numerical outcome estimates and their uncertainty, readers cannot quantify the result or judge its precision. A design can be informative in principle while a registry record remains insufficient for evaluating the treatment effect.

It also highlights the importance of distinguishing a planned comparison from the trial’s eventual course. The study was randomized and parallel-group, but the sponsor later decided to halt enrollment and terminate the study, with a treatment switch described for participants entering Part 2. Such changes make it especially important to know which participants contributed to each endpoint, how treatment transitions were handled, and what analysis was prespecified. Those details are not reported in the registry record.

The listed enrollment is 12, while group-level event counts are also limited. In general, estimates based on limited information may be imprecise, and a small number of observations can have substantial influence on summaries. The numerical precision of the primary comparison cannot be assessed because its estimates and intervals are not reported. The safety counts likewise should be read descriptively rather than as stable comparative rates.

Finally, the record shows why statistical reporting matters beyond a p-value. Readers need an effect estimate, uncertainty, analysis-population details, missing-data methods, and an account of multiplicity to understand what the data can support. The registry identifies a set of secondary outcomes and provides some safety counts, but it does not report the analysis plan or primary endpoint results. The key statistical lesson is that the trial question can be described, while the available record does not permit a quantitative answer to it.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this trial is the absence of numerical results for its primary endpoint. The registry record gives the endpoint definition and population but does not report group means, mean changes, a between-group estimate, confidence intervals, or a test result. There are also no analysis entries reported. The treatment effect and its precision therefore cannot be assessed from the registry record.

Enrollment was 12, and the record does not report group sizes for the primary analysis or the number with Week 24 data. It is not possible to determine how many participants contributed to the endpoint or whether missing measurements differed between groups. The approach to missing data, withdrawals, and treatment discontinuation is not reported in the registry record.

The study was terminated after the sponsor decided to halt enrollment permanently. The reason beyond that decision is not reported in the registry record. The record describes a switch to open-label BCX9930 for the C5-inhibitor group in Part 2 before Week 24, if earlier. This makes details of follow-up and analysis important, but those details are not available in the registry description of the primary result.

The registry does not report the randomization ratio, allocation procedure, statistical analysis plan, sample-size justification, or any interim-analysis plan. It also does not report how multiplicity across the listed outcomes was handled. The BCX9930 dosing description for newly enrolled participants is incomplete. Finally, the serious adverse event term percentages lack enough accompanying context in the record to establish a group assignment or denominator. These gaps limit both efficacy and safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants With Inadequate Response to C5 Inhibitor Therapy — NCT05116774.
• Registry record last updated 2025-03-07; status last verified 2025-03.
• Results first posted 2025-03-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT05116774 is a randomized, open-label, multicenter, parallel-group Phase 2 study of oral BCX9930 monotherapy compared with continued C5-inhibitor therapy in adults with PNH and residual anemia despite C5-inhibitor treatment. The registry lists enrollment of 12 and status as terminated. Its primary endpoint was change from baseline in hemoglobin at Week 24, measured in g/dL, among Part 1 ASaT participants with available data.

The sponsor decided to halt enrollment permanently and terminate the study. The registry describes a Part 2 switch to open-label BCX9930 for participants in the C5-inhibitor group before Week 24, if earlier. It reports selected serious and other adverse-event counts and lists serious adverse event terms with percentages. Numerical primary endpoint results, analysis entries, and key statistical-analysis details are not reported in the registry record, so the treatment effect and its precision cannot be evaluated.