Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT03053102), a na phase 2 study. The primary outcome is Change From Baseline In Serum LDH Levels At Day 28.

2. Clinical Question

In practical statistical terms, this is a within-group question: what change was recorded during the study among the participants who contributed endpoint data? Without a comparator group, the result cannot by itself distinguish a change associated with study participation from changes that might have occurred for other reasons. The registry’s description sets out the intended measurement and analysis population, but does not give the numerical Day 28 result needed to quantify the direction or size of the recorded change.

3. Trial Design

This was a Phase 2, open-label, single-group study of danicopan in participants with PNH who were currently untreated. The registry lists enrollment of 10 and status as completed. The recorded study start was 2017-03-31 and the primary completion date was 2018-11-14. The sponsor was Alexion Pharmaceuticals, Inc.

All participants were assigned to the Danicopan group in the registry’s arm description. The study was not described as randomized: allocation is listed as NA. Masking is listed as none, so the study was open label rather than blinded. No parallel control arm is described. The registry specifically flags that this is not a randomized comparison and that the arms are not a like-for-like control comparison. As a single-group study, its primary endpoint is interpreted as change over time within the treated group, not as a difference between treatment groups.

The intervention description states that starting doses ranged from 100 to 150 mg three times daily. Subsequent escalation up to 200 mg three times daily was based on clinical and biochemical response for 28 days in Part 1. The remaining arm-description text is incomplete in the registry record, so further details about treatment after that period are not reported in the registry record.

The primary endpoint was change from baseline in serum LDH at Day 28. The registry also lists secondary outcomes concerning hemoglobin at Days 28 and 84; serum LDH at Day 84; PNH type III red blood cell clone size; adverse events and laboratory abnormalities; and pharmacokinetic measures. The registry lists 11 outcome measures, but it reports no analyses for the outcome records in this dataset. The detailed protocol, planned sample-size justification, and statistical analysis plan are not reported in the registry record. The small enrollment and lack of a comparator are important context for interpreting any within-group observations, particularly because the numerical primary result is 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 2 parts. In Part 1, participants received danicopan for 28 days. Starting doses were 100 or 150 milligrams (mg) three times daily (TID). A further dose increase up to 175 mg TID (N=8 participants) and 200 mg TID (N=4 participants) was conducted. Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2).

Study Part 1: 28-Day Treatment

Study Part 2: 84-Day Treatment

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.

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: All participants who were enrolled in the study and received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline In Serum LDH Levels At Day 28, measured over Baseline, Day 28.

The primary endpoint is change from baseline in serum lactate dehydrogenase (LDH) at Day 28, measured in international units per liter (IU/L). The registry defines the change as the Day 28 serum LDH level minus the baseline serum LDH level. A negative change therefore represents a lower measured value at Day 28 than at baseline, while a positive change represents a higher measured value; this is a general interpretation of the stated subtraction, not a claim about the study’s observed result.

LDH is a biochemical measurement. In general, a continuous endpoint such as serum LDH can be summarized using a mean change to describe the average within-participant shift, and a standard deviation to describe variability in observed changes. The registry specifies those summary measures, but neither the numerical mean nor the standard deviation is reported in the registry record. The number of participants included in the primary endpoint calculation is also not reported in the registry record.

The endpoint is based on measurements at baseline and Day 28. The population definition includes participants who received at least 1 dose and had analyzable data at the specified timepoints. In general, requiring both timepoints allows a change score to be calculated for each participant with paired measurements. The registry does not report how many participants had usable measurements at both times, whether any measurements were missing, or how missing endpoint data were handled.

A within-group change can describe what was observed during the study, but it does not establish that the intervention caused the change. Without a control group, other explanations for change cannot be separated from an intervention effect using this endpoint alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

The primary measure is a continuous change score: each participant’s Day 28 serum LDH value minus that participant’s baseline value. A group mean of these changes describes the average measured shift among participants included in the endpoint analysis. This is not the same quantity as comparing the average Day 28 value with the average baseline value if the participants contributing at each timepoint differ. In general, paired change calculations use data from participants with information at both timepoints, but the actual endpoint denominator and missing-data procedure are not reported in the registry record.

The registry identifies the summary statistic as a mean and the dispersion measure as a standard deviation. In general, the mean describes the central average, while the standard deviation describes how spread out participant-level values are around that average. A standard deviation is not a confidence interval: it describes variability among observations, whereas a confidence interval describes uncertainty around an estimated quantity under specified assumptions. No numerical mean or standard deviation for the primary endpoint is reported in the registry record, and no confidence interval is reported there.

What can a within-group result establish?

For a single-group study, a change from baseline is a descriptive before-and-after estimate in the observed cohort. In general, a randomized control group can help distinguish treatment-associated changes from changes that may arise over time or from other factors. This study has no control group, and allocation is listed as NA. Consequently, even if the numerical change were available, it would not by itself provide a randomized estimate of the difference between danicopan and a comparator.

Open-label status means masking was absent. In general, lack of masking can influence subjective assessments, participant behavior, or decisions about care and measurement. The primary outcome is a laboratory measurement, but open-label design does not remedy the absence of a control group or establish that any within-group change was caused by treatment. The registry does not report further details about laboratory procedures or efforts to reduce measurement bias.

How should precision be considered?

Precision concerns how narrowly the data support an estimate. In general, a confidence interval combines the estimated effect with its uncertainty; a narrower interval indicates greater precision under the assumptions used, while a wider interval indicates greater uncertainty. The record does not provide a confidence interval, standard error, or analyzed endpoint count for the primary measure. Precision therefore cannot be evaluated from the registry information. Enrollment of 10 is a study-level figure, not confirmation that 10 participants contributed to every endpoint.

In general, a small cohort can yield estimates that are sensitive to individual observations, especially when participant outcomes vary. That is a statistical consideration, not a claim about the observed variability in this study. The missing primary result and analyzed count prevent assessment of how much influence individual measurements may have had.

What do hypothesis tests and p-values tell readers?

In general, a p-value evaluates how compatible data are with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment works, and it does not convey the magnitude or clinical importance of an effect. Interpretation depends on the hypothesis, analysis method, and assumptions. No p-value or analysis record is reported for the primary endpoint, and the registry does not describe the planned hypothesis test. Therefore, no statistical-significance conclusion can be drawn from the record.

Even if a p-value were available, it would not replace an effect estimate and uncertainty interval. A complete interpretation ordinarily considers the size and direction of the estimate, its precision, and the design limitations. For this record, the numerical estimate and inferential results are not reported in the registry record, so those aspects cannot be assessed.

What do the planning assumptions mean?

Sample-size planning is different from reporting results. The planning assumptions describe an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence that this single-group study randomized participants between two arms. They are also not observed power. No numerical planning sample sizes are reported in the registry record described by these registry entries.

In general, a planning calculation asks how many participants would be needed under specified assumptions to detect a chosen effect with a target level of power. Changing the assumed effect or variability can change the resulting planning estimate. Such an estimate is not a retrospective measure of whether the completed study “had enough power,” and it cannot substitute for the observed effect and its uncertainty. The two-arm planning assumptions should be kept separate from the actual study design, which is recorded as single group with no randomized comparator.

These methods concepts help explain what would be needed to interpret a continuous endpoint, but they do not fill gaps in the registry record. The primary mean, standard deviation, endpoint count, confidence interval, p-value, and prespecified analysis details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary Day 28 serum LDH change and secondary measures involving hemoglobin, later LDH, red blood cell clone size, safety, laboratory abnormalities, and pharmacokinetics. When a study examines multiple outcomes, timepoints, or statistical tests, there can be more opportunities for apparently notable findings to arise by chance. In general, a multiplicity strategy may define a primary outcome, adjust testing, or treat secondary findings as exploratory. The registry record does not report whether any multiplicity adjustment or testing hierarchy was planned.

The listed primary outcome is distinguishable from the secondary outcomes, but the record does not provide analysis results or a statistical analysis plan. The number of outcome measures is not the number of successful tests, and the registry lists no analyses for the outcome records in the registry record. No claim about statistical significance across outcomes is therefore supported.

The primary analysis population is described as participants who received at least 1 dose and had analyzable data at the specified timepoints. This description does not state the number actually analyzed. The registry record does not report missing-data counts, reasons for missingness, imputation methods, sensitivity analyses, or whether all enrolled participants contributed to each secondary outcome. In general, missing-data methods can affect estimates when measurements are unavailable, especially if missingness is related to participant outcomes. The extent or impact of missing data in this trial cannot be determined from the record.

It is also not reported in the registry record whether the primary analysis population was defined before results were known, or whether any protocol deviations affected inclusion. These omissions do not establish that problems occurred; they limit what can be assessed from the posted information. The endpoint description specifies who was eligible for the primary calculation, but not how the actual analysis handled incomplete records.

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: haemolysis (10.0%), alanine aminotransferase increased (10.0%), aspartate aminotransferase increased (10.0%).

The registry reports 10 participants at risk for serious adverse events, with 1 participant affected, and 10 at risk for other adverse events, with 9 affected. It reports 0 deaths. These are participant counts as recorded for the Danicopan group. The registry also lists haemolysis, alanine aminotransferase increased, and aspartate aminotransferase increased among the top serious adverse-event terms, each at 10.0%.

These figures describe events recorded during the study; they do not establish that danicopan caused an event. In general, adverse-event reporting records occurrences in a defined study context, and attribution requires additional information about timing, clinical assessment, and alternative explanations. The registry does not provide those details in the registry record for this analysis.

The 1 participant affected by a serious adverse event and the 9 affected by other adverse events are distinct summary counts. The listed event terms should not be added together to infer a total number of affected participants: participants may experience more than one event, and the registry record does not specify overlap for these terms. Nor do these counts establish the frequency of events outside the study cohort. With enrollment of 10 and no comparator group, the safety figures are descriptive rather than a comparative estimate of risk.

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

The record documents a Phase 2, open-label study of danicopan in currently untreated participants with PNH. It identifies a primary endpoint focused on mean change in serum LDH between baseline and Day 28 and defines the population eligible for that calculation. This information clarifies what the study set out to measure. It does not give the numerical primary result: the mean change, standard deviation, analyzed participant count, and uncertainty interval are not reported in the registry record.

Accordingly, the registry information does not establish the direction or size of the observed Day 28 LDH change, nor how precisely that change was estimated. The absence of a reported estimate should not be read as evidence that the endpoint showed no change. It means the result needed to make that assessment is not reported in the registry record.

The study design also determines what any within-group change could mean. With one group and no randomized comparator, a change from baseline would describe what happened among participants during the study, not the contrast between danicopan and an alternative. A before-and-after result alone cannot rule out other explanations for change. Open-label status and the absence of masking provide further context, although the record does not describe specific measurement procedures or bias assessments.

The safety counts describe participants affected by reported events in the study group, and the listed terms give additional descriptive information. They do not establish causation or comparative safety. The registry’s secondary outcome list similarly identifies areas assessed, but those outcome listings do not substitute for numerical results.

In general, statistical interpretation is strongest when the effect estimate, its precision, the analysis population, and the design are considered together. Here, the design and endpoint definition are described, but key numerical results and analysis details are not reported in the registry record. The appropriate conclusion is therefore limited: this record describes the study question and design, while leaving the primary effect and its precision undetermined.

13. Why This Trial Matters Statistically

This study is statistically useful to examine because it illustrates the distinction between a clearly defined endpoint and an interpretable reported result. The registry specifies a continuous measure, a baseline-to-Day 28 change, a mean summary, a standard deviation, and an eligible analysis population. Those elements tell readers what quantity was intended. Yet without the observed mean, spread, analyzed count, or uncertainty interval, the magnitude and precision of the result cannot be evaluated.

The single-group design is another important statistical feature. Within-participant change can be informative as a description of an observed cohort, but it is not a randomized treatment contrast. A control group helps address what might have occurred over the same period without the intervention. Since this study has no control arm, the design cannot provide that comparison. This distinction is particularly important when readers encounter a change-from-baseline endpoint and are tempted to interpret it as a causal treatment effect.

The record also shows why enrollment and analysis denominators should not be treated as interchangeable. Enrollment is 10, while the primary endpoint population requires receipt of at least 1 dose and analyzable data at the specified timepoints. The actual number contributing to the primary calculation is not reported in the registry record. In general, knowing the denominator is necessary to assess precision and understand whether incomplete measurements could affect the result.

Finally, a list of outcomes is not equivalent to a report of statistical findings. The registry identifies 11 outcome measures and multiple measurement domains, but no analysis records are listed. That gap highlights the importance of complete outcome reporting alongside a protocol-defined question. Readers can identify what was to be assessed, but not determine from this record what the primary analysis found.

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 trial-specific limitation for interpretation is that the numerical primary endpoint result is not reported in the registry record. The record gives the endpoint definition and summary-statistic type, but not the observed mean change, standard deviation, analyzed sample size, confidence interval, or p-value. The primary outcome’s direction, magnitude, and precision therefore cannot be assessed.

Enrollment was 10, but the primary analysis population is defined by treatment exposure and analyzable measurements at specified timepoints. The actual endpoint denominator is not reported in the registry record. Missing-data counts, reasons for missingness, and methods for handling incomplete measurements are also not reported in the registry record.

The design is open label and single group, with allocation listed as NA and no comparator. This prevents a randomized estimate of a treatment contrast and limits causal interpretation of any within-group change. The trial’s enrollment and design also mean that the safety counts are descriptive for this cohort; they do not provide a comparative assessment.

Although the registry lists 11 outcome measures, it records no analyses for them in the registry record. A statistical analysis plan, multiplicity approach, protocol details, sample-size justification, interim analysis plans, and prespecified handling of protocol deviations are not reported in the registry record. These are unknowns, not evidence that the corresponding procedures were absent. The arm description is truncated after the Part 1 dosing information, so subsequent treatment details are not reported in the registry record. Together, these gaps constrain assessment of both the results and the analysis choices.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) — NCT03053102.
• Registry record last updated 2022-06-23; status last verified 2022-05.
• Results first posted 2021-06-02.
• 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

NCT03053102 is a completed Phase 2, open-label, single-group study of danicopan in currently untreated participants with PNH. Enrollment was 10. The recorded study start was 2017-03-31 and primary completion was 2018-11-14. The registry describes starting doses of 100 to 150 mg three times daily, with escalation up to 200 mg three times daily based on clinical and biochemical response for 28 days in Part 1.

The primary endpoint was mean change from baseline in serum LDH at Day 28, with standard deviation. The endpoint population was participants who received at least 1 dose and had analyzable data at the specified timepoints. The numerical primary result and the analyzed endpoint count are not reported in the registry record. No randomized comparator is described, and the registry lists no outcome analyses. Safety reporting includes 1 participant affected by a serious adverse event among 10 at risk, 9 affected by other adverse events among 10 at risk, and 0 deaths.