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 A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN (NCT03124368), a non-randomized phase 2 study. The primary outcome is Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03124368 |
| Phase | Phase 2 |
| Condition | C3 Glomerulonephritis, Dense Deposit Disease, C3 Glomerulopathy |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alexion Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
The study asked whether danicopan was followed by an increase in serum C3 levels among participants with low C3 attributed to C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN). Its primary question was framed around change from baseline in C3 on Day 15. This is a biomarker question: the endpoint measures a laboratory value, not a clinical event or a direct measure of how participants felt or functioned.
Population
Participants with low C3 levels due to C3G or IC-MPGN. The primary endpoint population was those who received at least one dose and had a baseline measurement and at least one measurement during treatment.
Intervention
Danicopan, given three times per day. One group received 100 mg; the other received up to 200 mg, with dosing dependent on safety, pharmacokinetic, and pharmacodynamic data from the sentinel group.
Comparator
There was no randomized or untreated control group. The study used two sequential danicopan groups, so they are not a like-for-like control comparison.
Primary question
What was the change from baseline in serum C3 levels on Day 15 during danicopan treatment? The numerical change and its variability are not reported in the registry record.
The record identifies C3G and IC-MPGN as the conditions of interest and specifies blood C3 as the central measure. Other recorded outcomes included complement pathway activity, Bb, pharmacokinetic measures, time to peak serum C3, and adverse events. Those outcomes broaden the study’s biological and safety observations, but do not change the primary question: whether the measured C3 level changed between baseline and Day 15.
3. Trial Design
This was a Phase 2a proof-of-mechanism study, described as open-label. It was nonrandomized, had no masking, and used a sequential model. The registry lists enrollment as 6 and the study status as completed. The record gives a start date of 2017-08-09 and a primary completion date of 2018-12-21.
Participants were assigned to sequential treatment groups rather than randomized to concurrent treatment strategies. Group 1 was the sentinel group and received danicopan 100 mg three times per day during the treatment period. Group 2 received up to 200 mg three times per day. Its dose depended on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1. These features mean that dose and group membership were connected to the sequence of study conduct.
Because there was no placebo or other control group, the study does not provide a randomized comparison of danicopan against an alternative. Differences between the two groups, if considered, would also need to be interpreted in light of the sequential design and different dosing descriptions. The record explicitly cautions that the groups are not a like-for-like control comparison.
The primary endpoint was change from baseline in serum C3 on Day 15. The endpoint description defines change as the Day 15 value minus the baseline value, with results intended to be expressed in g/L. The listed primary analysis population comprised participants who received at least one dose and had both a baseline measurement and at least one measurement during treatment. Details of further eligibility criteria, treatment duration beyond the endpoint timing, and the statistical plan are not reported in the registry record.
The sequential, open-label structure is consistent with an early proof-of-mechanism question, but it limits what can be inferred from between-group comparisons. Without randomization or a concurrent untreated group, observed changes cannot be separated from other influences by a controlled comparison. The record does not report additional design features that would resolve that limitation.
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 | Group 1: Danicopan 100 mg TID (Sentinel) | Group 2: Danicopan up to 200 mg TID |
|---|---|---|
| STARTED | 2 | 4 |
| Received at Least 1 Dose of Study Drug | 2 | 4 |
| COMPLETED | 2 | 4 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period.
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 received at least 1 dose of danicopan.
| Characteristic | Unit | Group 1: Danicopan 100 mg TID (Sentinel) | Group 2: Danicopan up to 200 mg TID | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 4 | 6 | |
| Age, Continuous | years | 25.50 (SD 7.85) | 30.00 (SD 12.68) | 28.50 (SD 10.69) |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 5 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 3 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15, measured over Baseline, Day 15.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | g/L |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in serum C3 complement protein levels on Day 15. Serum C3 was measured using a conventional Roche immunoturbidimetric assay. The stated unit was g/L, and change was defined as the Day 15 level minus the baseline level. Under that definition, a positive change represents a higher measured value at Day 15 than at baseline; a negative change represents a lower measured value.
This endpoint was selected to address the study’s proof-of-mechanism objective: determining whether danicopan increases blood C3 levels in participants whose low C3 was due to C3G or IC-MPGN. A laboratory biomarker can provide a direct, measurable way to examine a biological question over the study’s specified measurement period. It is not, by itself, a measure of symptoms, kidney function, long-term disease course, or a clinical benefit.
The analysis population was defined by treatment exposure and availability of measurements: at least one danicopan dose, a baseline measurement, and at least one measurement during treatment. That definition matters because participants without the required measurements would not be represented in the primary endpoint population. The registry does not report the number meeting those criteria or the numerical mean change and standard deviation. Thus, the endpoint and its measurement method are specified, but the size and precision of the observed change are not available in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines the primary outcome and its measurement but does not report numerical results for mean change in serum C3, its standard deviation, or an interval estimate. As a result, the magnitude, direction, and precision of the primary endpoint cannot be described from this record. It is not possible to determine from the posted information whether the average Day 15 value was higher or lower than baseline, or how variable individual measurements were.
The study enrolled 6 participants. That enrollment figure describes the study as a whole; the record does not state how many participants contributed to the primary endpoint analysis. The analysis population required receipt of at least one dose, a baseline measurement, and at least one measurement during treatment. Enrollment and the endpoint analysis population should therefore not be treated as interchangeable without a reported analysis count.
The study design also shapes interpretation. It was open-label and nonrandomized, with sequential groups and no concurrent control. Group 1 received 100 mg three times per day, while Group 2 received up to 200 mg three times per day based on data from the sentinel group. Comparisons between these groups would not isolate a dose effect: group assignment was sequential, dose descriptions differed, and the record cautions that the groups are not a like-for-like control comparison. The design can describe observations during treatment, but it cannot establish what would have happened over the same period without danicopan.
The Day 15 biomarker endpoint addresses a short-term laboratory question. It does not directly establish changes in clinical outcomes or longer-term effects. Other outcomes listed in the registry include classical and alternative complement pathway activity, time to peak serum C3, Bb, pharmacokinetic measures, and adverse events. Their inclusion indicates additional measures of interest; numerical results for those outcomes are not stated in the record.
Any planning illustrations based on an observed effect should be read as hypothetical planning exercises, not as evidence about the reliability of this study’s result. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such calculations are not observed power and do not compensate for the absence of a reported primary effect estimate. Since no numerical primary result appears in the registry record, the result’s statistical precision cannot be judged from the available endpoint information.
Overall, the record supports describing the study question, design, endpoint definition, and limited enrollment. It does not support a numerical claim about the primary biomarker response. That distinction is central: a well-defined endpoint does not, by itself, reveal the observed result.
9. Statistical Methods Explained
The primary measure is continuous: serum C3 is recorded on a numerical scale, and the endpoint is a numerical change between two measurements. The registry describes the summary parameter as a mean and the measure of dispersion as a standard deviation. A mean describes the average change in the analysis population; a standard deviation describes how spread out individual changes are around that average. These answer different questions. The mean concerns the central tendency, while the standard deviation concerns variability among measured changes.
What does change from baseline represent?
The endpoint definition is Day 15 serum C3 minus baseline serum C3. This signed subtraction preserves direction. A value above zero would indicate an increase relative to baseline, and a value below zero would indicate a decrease. That interpretation follows from the endpoint definition; it is not a statement about the actual study result, which is not numerically reported in the registry record. The stated unit is g/L, so the change is expressed on the same measurement scale as the serum level.
Why report a mean and standard deviation?
For a continuous endpoint, a mean provides a compact description of the average observed change. It can be useful for a proof-of-mechanism question because the objective concerns whether a measured laboratory level changes. But an average alone does not show whether individual participants had similar changes or widely differing changes. The standard deviation supplies information about that spread. Neither statistic, on its own, establishes how precisely the average has been estimated. The record does not report the numerical mean or standard deviation for this endpoint, so those features cannot be assessed from the posted endpoint information.
What would a confidence interval add?
In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. It communicates uncertainty around an estimate, rather than only describing the estimate itself. A narrower interval generally indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. This is a general statistical explanation, not a description of an interval reported for this study. A numerical confidence interval for the primary endpoint is not reported in the registry record.
Why does the design matter for statistical interpretation?
Randomization can help make treatment groups comparable with respect to measured and unmeasured factors, on average, and a concurrent control can provide a reference for changes that might occur without the study treatment. This trial was nonrandomized, sequential, and open-label, and it had no concurrent control. As a result, a before-and-after change would describe what was observed among treated participants, but it would not by itself distinguish treatment-associated change from other explanations. Open-label status also means masking was absent; the record does not describe procedures that would address this in measurement or reporting.
Sequential allocation is particularly relevant to any comparison of the two groups. The second group’s dose depended on safety, pharmacokinetic, and pharmacodynamic data from the sentinel group. The groups therefore differ not only in their dose descriptions but also in their sequence and the information used to set dosing. A comparison between them should not be read as though participants had been randomly assigned to two fixed doses under otherwise identical conditions. The registry explicitly notes that the arms are not a like-for-like control comparison.
How should planning calculations be understood?
The record describes sample-size calculations as planning illustrations based on the observed effect, not as the trial’s own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the calculation is expressed as participants per arm for 80% or 90% power; time-to-event calculations are described in terms of total events. These are planning quantities under assumptions, not counts observed in the trial and not retrospective proof that the study had a particular probability of detecting an effect.
Because the numerical observed primary effect is not reported in the registry record, a reader cannot evaluate the magnitude on which an observed-effect-based illustration depends. In general, planning values calculated from an observed effect can be sensitive to that estimate, especially when the estimate is uncertain. Such illustrations should therefore not be mistaken for prespecified sample-size justification or for a replacement for an explicitly reported analysis plan. The protocol’s sample-size justification and statistical plan are not reported in the registry record.
What does over-dispersion mean in general?
Over-dispersion refers generally to data varying more than a model’s assumptions expect. When present, uncertainty estimates based on an assumption of less variability can be too optimistic. That concept is not a reported finding from this study. The primary endpoint is a continuous measurement summarized with a mean and standard deviation, and the registry record does not report a model-based analysis or a finding of over-dispersion. The concept is relevant only as general background on why the choice of statistical model and variability assumptions matters.
Finally, statistical significance and biological or clinical importance are distinct concepts. A significance test, when reported, evaluates how compatible data are with a specified statistical model and null hypothesis. It does not by itself establish that a change matters to participants or predicts a clinical outcome. No primary endpoint test result or p-value is reported in the registry record, and the endpoint is a biomarker rather than a direct clinical outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures, including the primary C3 endpoint and secondary measures involving complement pathway activity, time to peak serum C3, adverse events, pharmacokinetics, and Bb. Considering multiple outcomes can create a multiplicity issue: when many statistical tests are performed, the chance of at least one apparently notable result can increase. Statistical plans may address this through prespecified hierarchies, adjustments, or descriptive interpretation. Which approach, if any, was planned for this study is not reported in the registry record.
The record lists 0 analyses. This should be read as the number of analysis entries recorded, not as evidence that investigators performed no statistical work. No detailed testing strategy, model specification, multiplicity adjustment, or interim-analysis plan is reported in the registry record. The available information does not establish whether the secondary outcomes were intended as confirmatory tests or exploratory measures.
The primary analysis population required at least one dose, a baseline C3 measurement, and at least one measurement during treatment. The registry does not report how many participants met these criteria, how missing endpoint measurements were handled, or whether any imputation or sensitivity analysis was used. It also does not report reasons for missing measurements or the extent of missingness by group. These details matter because analyses limited to participants with observed measurements can be affected if measurement availability is related to participant characteristics or outcomes.
Accordingly, interpretation should distinguish the stated endpoint population from the enrolled group and should not presume that all enrolled participants contributed to every outcome. The analysis population definition is reported; the actual analysis count and missing-data procedures are not reported in the registry record.
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 |
|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | 0 | 2 | 0.0% |
| Group 2: Danicopan up to 200 mg TID | 1 | 4 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | 0 of 2 |
| Group 2: Danicopan up to 200 mg TID | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | 2 of 2 |
| Group 2: Danicopan up to 200 mg TID | 3 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: Danicopan 100 mg TID (Sentinel) | Group 2: Danicopan up to 200 mg TID |
|---|---|---|---|
| Presyncope | Nervous system disorders | 0 of 2 | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: Danicopan 100 mg TID (Sentinel) | Group 2: Danicopan up to 200 mg TID |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 2 | 1 of 4 |
| Dizziness | Nervous system disorders | 1 of 2 | 0 of 4 |
| Upper respiratory tract infection | Infections and infestations | 1 of 2 | 0 of 4 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 2 | 0 of 4 |
| Diarrhoea | Gastrointestinal disorders | 1 of 2 | 0 of 4 |
| Hypotension | Vascular disorders | 0 of 2 | 1 of 4 |
| Headache | Nervous system disorders | 0 of 2 | 1 of 4 |
| Pain | General disorders | 0 of 2 | 1 of 4 |
| Crepitations | General disorders | 0 of 2 | 1 of 4 |
| Prerenal failure | Renal and urinary disorders | 0 of 2 | 1 of 4 |
Serious events with the highest arm-level rate: presyncope (25.0%).
The safety figures are reported separately for the two sequential treatment groups. In Group 1, 2 participants were listed as at risk for serious adverse events and 0 were listed as affected. In Group 2, 4 were listed as at risk and 1 was listed as affected. The record also lists 0 deaths in each group. These are participant counts, not rates of treatment causation, and they do not establish that danicopan caused or prevented an event.
For other adverse events, the record lists 2 affected participants in Group 1 and 3 in Group 2, with the corresponding at-risk counts shown as 2 and 4. These figures should be kept distinct from the serious adverse event counts. The listed serious adverse event term is presyncope at 25.0%; the registry record does not supply additional context for interpreting that percentage in the information.
The study also listed serious adverse events, Grade 3 and Grade 4 treatment-emergent adverse events, and adverse events leading to discontinuation among its outcomes. A detailed numerical breakdown for those categories is not reported in the registry record. With a small enrolled study, these counts are descriptive and cannot characterize uncommon risks reliably. The sequential, nonrandomized design also does not support a controlled safety comparison between groups.
12. What the Result Does, and Does Not, Mean
This record describes an early, open-label proof-of-mechanism study asking whether serum C3 changed during danicopan treatment in participants with low C3 due to C3G or IC-MPGN. It identifies the primary endpoint, the assay, the measurement timing, and the endpoint population definition. Those details clarify what the study intended to measure.
However, the numerical primary endpoint results are not reported in the registry record. Without the mean change and its variability, the posted information does not establish the direction or size of the average C3 change or how consistent the changes were. It also does not provide a numerical basis for judging the precision of the estimate. The endpoint’s existence should not be confused with a reported result.
Even if a before-and-after change were available, this design would not establish that danicopan caused the change. There was no randomized or untreated control group, and the two treatment groups were sequential rather than like-for-like comparators. Natural variation, measurement timing, and other influences could not be separated from treatment-associated change by a controlled comparison on the basis of this design alone.
The endpoint is a blood biomarker measured at Day 15. It does not directly tell readers about symptoms, kidney function, long-term disease course, or clinical benefit. Other biological, pharmacokinetic, and safety outcomes were listed, but numerical results for those outcomes are not stated in the registry information.
The appropriate reading is therefore narrow: the registry documents a study designed to examine a short-term C3 biomarker question and records some group-level safety counts. It does not, in the available information, provide the numerical primary result needed to assess the observed biomarker change, nor does the design support a controlled causal conclusion.
13. Why This Trial Matters Statistically
Statistically, this study is informative as an example of how a proof-of-mechanism question differs from a comparative treatment question. Its primary endpoint is a continuous laboratory measure assessed as change from baseline, and the study’s objective focuses on whether that measured value changes during treatment. This can organize a biological investigation, but the inference remains tied to the endpoint and design used.
The sequential structure also makes the distinction between dose groups important. The sentinel group received 100 mg three times per day; the later group received up to 200 mg three times per day according to safety, pharmacokinetic, and pharmacodynamic information from the first group. This is a dose-escalation sequence, not a randomized comparison of fixed strategies. Recognizing that distinction prevents a group contrast from being interpreted as a clean causal estimate of dose differences.
The study also illustrates why effect estimates and uncertainty need to be reported together. A mean change would describe the average, while a dispersion measure and an interval estimate would help readers understand variability and precision. The registry describes the intended mean and standard deviation summaries, but does not report the numerical primary endpoint results in the information. Without those values, a reader cannot assess the observed effect’s magnitude or precision.
Finally, the stated enrollment of 6 and the descriptive adverse-event counts underline the limited scope of the evidence. Such information can characterize what was recorded in this study, but it cannot stand in for a controlled comparison or a broader assessment of uncommon events. The main statistical lesson is to keep the biological question, the endpoint, the study design, and the limits of the reported results aligned when interpreting a proof-of-mechanism record.
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 principal limitation for interpreting the primary endpoint is that its numerical results are not reported in the registry record. Although the endpoint, unit, measurement method, timing, and summary approach are specified, the mean change and standard deviation are unavailable. The record therefore does not permit assessment of the observed direction, magnitude, variability, or precision of the primary result.
The study enrolled 6 participants, and the number included in the primary endpoint population is not reported. That population was restricted to participants with treatment exposure and both baseline and on-treatment measurements. Without an analysis count or missing-data details, the relationship between enrollment and the endpoint analysis cannot be evaluated.
The trial was open-label, nonrandomized, sequential, and lacked a concurrent control group. These features limit causal interpretation of within-participant changes and make direct comparisons between treatment groups unsuitable as randomized dose comparisons. Group 2 dosing also depended on data from the sentinel group, so group and treatment sequence were linked.
The primary assessment was at Day 15, limiting the question to the specified short-term measurement. The endpoint is a biomarker and does not directly report clinical outcomes. The registry does not report the statistical plan, sample-size justification, missing-data procedures, multiplicity strategy, or interim-analysis details. Numerical results for the listed secondary outcomes are also not included in the information. These limitations constrain both the interpretation of the biological response and the broader conclusions that could be drawn from the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN — NCT03124368.
- Registry record last updated 2021-11-04; status last verified 2021-10.
- Results first posted 2021-07-13.
- 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.
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18. Record Summary
NCT03124368 is a completed Phase 2a, open-label, nonrandomized, sequential study of danicopan in participants with low C3 due to C3G or IC-MPGN. The registry lists enrollment as 6. Group 1 received 100 mg three times per day; Group 2 received up to 200 mg three times per day based on available data from the sentinel group.
The primary endpoint was change from baseline in serum C3 on Day 15, measured by a conventional Roche immunoturbidimetric assay and expressed in g/L. The registry defines the analysis population by treatment exposure and availability of baseline and on-treatment measurements, but the numerical primary result and its analysis count are not reported in the registry record.
The record includes additional biological, pharmacokinetic, and safety outcomes. It reports serious adverse event counts of 0 in Group 1 and 1 in Group 2, with 0 deaths listed in each group. The nonrandomized, sequential design does not provide a like-for-like control comparison.