A Study to Evaluate Zilucoplan Injected Subcutaneously Either by a Prefilled Syringe or an Auto-injector in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Zilucoplan Injected Subcutaneously Either by a Prefilled Syringe or an Auto-injector in Healthy Adult Participants (NCT06511076), a randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan.

2. Clinical Question

This is a comparison of two ways of administering the same drug, not a comparison of zilucoplan with no treatment or with a different drug. The population was healthy adults, so the primary question concerns pharmacokinetic similarity between delivery devices in that population. It does not directly address how the devices perform in people with a medical condition or in routine care.

The trial was randomized and used a two-way crossover design. In a crossover study, participants receive the compared treatments in different sequences, allowing measurements from the same person to contribute to both treatment conditions. That design can reduce the influence of stable differences between participants. It also makes period, sequence, and carryover considerations relevant to interpretation; details about those considerations and their handling are not reported in the registry record.

3. Trial Design

The registry record describes an open-label, single-center, randomized, two-way crossover, single-dose study in healthy adult participants. It is listed as a Phase 1 study and as completed. The record gives enrollment as 14 and identifies UCB Biopharma SRL as the sponsor. The recorded start date is 2024-08-05 and the primary completion date is 2024-11-26.

Participants were assigned to treatment sequence A-B or B-A. Treatment A was zilucoplan administered by prefilled syringe, the reference method; Treatment B was zilucoplan administered by autoinjector, the test method. Each treatment is described as a single subcutaneous injection. The sequence descriptions do not state a washout duration, the timing between treatments, or detailed scheduling beyond the stated treatment days. Those details are not reported in the registry record.

Open-label means that masking was not used, according to the record. The outcome of interest is a laboratory-based pharmacokinetic measure, but the registry record does not describe any blinding of laboratory personnel or the procedures used to protect outcome assessment from knowledge of treatment.

The primary outcome was area under the plasma concentration-time curve from predose to infinity for zilucoplan, measured from predose on Day 1 of each treatment period through predefined time points up to 816 hours (Day 35) after dosing. The pharmacokinetic analysis population is defined as randomized participants who received at least 1 dose and had at least 1 observable pharmacokinetic concentration measurement. The actual number included in that population and any exclusions from it are not reported in the registry record.

The record lists 7 outcome measures, including the primary pharmacokinetic outcome and safety outcomes involving treatment-emergent adverse events and adverse device effects. It reports 3 analyses. A detailed protocol, treatment-period schedule, allocation procedure, and full statistical analysis plan are not reported in the registry record, so further design details should not be inferred.

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 Participant Flow refers to the All randomized Study Participants.

Treatment Period 1 (35 Days)

Treatment Period 2 (35 Days)

Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic (PK) Set consisted of all study participants who were randomized, received at least 1 dose of ZLP, and had at least 1 observable PK concentration measurement.

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: Baseline refers All Randomized Study Participants which consisted of all study participants who were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan, measured over Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose.

The primary endpoint is the area under the plasma concentration-time curve from time zero, defined as predose on Day 1, to infinity for zilucoplan. It is expressed in hour*nanogram per milliliters (h*ng/mL). The registry describes the endpoint as the area under the plasma concentration-time curve from predose to infinity, with blood sampling at predefined time points up to 816 hours (Day 35) after dosing.

Area under the curve represents cumulative drug exposure over time. In general, pharmacokinetic comparisons use it to assess whether two administration methods produce similar overall exposure, rather than to compare a single concentration at a single sampling time. Estimating exposure to infinity also incorporates the terminal part of the concentration-time profile beyond the final observed sample; the specific estimation procedures are not reported in the registry record.

The registry reports geometric means and geometric coefficients of variation for the treatment groups. Geometric summaries are commonly used for pharmacokinetic measurements because such measurements are often analysed on a logarithmic scale. The geometric coefficient of variation describes relative variability on a multiplicative scale; it is not the same as a standard deviation on the original scale.

The endpoint is relevant to a device comparison because a difference in delivery method could be associated with a difference in measured drug exposure. A similarity assessment requires an estimate of the relative exposure and its uncertainty, interpreted against the prespecified criteria for equivalence. The registry reports a 90% confidence interval for the model-based ratio, but equivalence margins and the complete decision rule are not reported in the registry record. Consequently, the numerical estimate can be described, while the full protocol-level basis for declaring equivalence cannot be reconstructed from the record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary comparison is reported as a geometric least-squares mean ratio from a mixed-effects model. In general, a mixed-effects model can represent both systematic treatment-related differences and variation associated with the structure of a study. In a crossover trial, participants receive more than one treatment, so observations from the same participant are related rather than independent. A model can account for that within-participant structure while estimating the treatment contrast. The registry identifies the model family but does not report the included effects or the exact specification.

What the ratio represents

A ratio compares quantities on a relative scale. For this endpoint, a ratio of 1 represents equal model-based geometric means for the compared treatments. The reported ratio is 0.981. The registry lists the groups in the order ZLP-PFS and ZLP-AI, with ZLP-PFS identified as the reference and ZLP-AI as the test. The exact numerator and denominator convention for the reported ratio is not stated in the analysis description, so the value is best described as the reported model-based ratio rather than assigning it a direction beyond the stated treatment comparison.

“Least-squares mean” refers to a model-based mean estimate, calculated with the model’s structure rather than simply averaging the observed values. The geometric version is typically obtained by modelling measurements on a logarithmic scale and returning the estimate to the original scale. That approach is commonly used for pharmacokinetic outcomes, where relative differences are often of interest and the distribution may be asymmetric. This is general statistical context; the registry does not describe the exact transformation and back-transformation procedures.

How to read the confidence interval

The reported 90% confidence interval runs from 0.953 to 1.010. In general, a confidence interval expresses the precision of an estimate under the statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval, while the interval endpoints show which values remain compatible with the data and model at the stated confidence level. It is not a range containing a fixed proportion of individual participants’ measurements, and it does not mean there is a 90% probability that the fixed treatment effect lies inside this particular interval.

For an equivalence assessment, the interval is usually evaluated against prespecified boundaries. The relevant boundaries and the complete decision procedure are not reported in the registry record. Without them, the interval can be described, but a formal equivalence conclusion cannot be checked from the registry result alone. The absence of a reported p-value does not prevent reading the estimate and interval; the registry lists no p-value for this analysis.

Geometric means and variability

The registry reports geometric mean exposure values of 950900.0 h*ng/mL for ZLP-PFS and 932700.0 h*ng/mL for ZLP-AI. It reports geometric coefficients of variation of 15.0 and 17.1, respectively. Geometric means are appropriate summaries for data analysed multiplicatively: on the logarithmic scale, multiplicative changes become additive. A geometric coefficient of variation summarizes relative spread and should not be read as an interval around the mean or as a standard deviation on the original measurement scale.

The group summaries are not the same as the mixed-model treatment estimate. A crossover model can account for the paired measurements and other design features, while a simple comparison of group-level summaries does not retain all participant-level pairing information. The model ratio and its confidence interval are therefore the reported inferential results; the group geometric means and coefficients of variation provide descriptive context.

Why crossover structure matters

In a crossover design, each participant can serve as their own comparison across treatments. In general, this can control for stable participant characteristics that might otherwise contribute to between-person variability. The validity and interpretation of the comparison also depend on how treatment periods, sequence, and possible carryover are handled. The record identifies the two sequences, A-B and B-A, but the washout schedule, period effects, sequence effects, and carryover assessment are not reported in the registry record. It is not appropriate to assume how those issues were addressed.

The trial was open-label, meaning masking was not used. The primary outcome is a measured concentration-derived pharmacokinetic endpoint, but details about laboratory blinding, sample handling, and assay procedures are not reported. These are relevant procedural details for assessing measurement quality, but their absence from the registry record does not establish that any particular problem occurred.

Analysis population and missing measurements

The registry defines the pharmacokinetic set as all randomized participants who received at least 1 dose of zilucoplan and had at least 1 observable pharmacokinetic concentration measurement. This definition indicates that inclusion required dosing and an observable concentration. The number included in the analysis, participant flow by treatment sequence, and handling of incomplete concentration profiles are not reported in the registry record. The approach to missing observations and any sensitivity analyses are also not reported.

For an endpoint extending to infinity, the analysis depends on the concentration observations and the method used to estimate the terminal portion of the profile. The registry gives the endpoint definition and sampling timeframe but does not describe the estimation method, rules for handling profiles that could not be characterized, or the proportion of exposure extrapolated beyond observed sampling. These details would be needed to assess the endpoint’s calculation fully.

Planning illustrations and analysis multiplicity

In general, sample-size planning illustrations based on an observed effect are not the same as observed power and do not describe the original trial’s design rationale. The stated illustration assumptions use 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. The registry record does not report the trial’s own sample-size justification, the chosen equivalence margins, or whether these assumptions formed part of its original planning.

The registry lists 7 outcome measures and 3 analyses. It does not report a complete multiplicity strategy explaining how inference across outcomes or analyses was controlled, nor does it identify a hierarchy of tests in the record. Multiplicity can affect the interpretation of multiple statistical tests because the chance of at least one false-positive result can increase as testing expands. That general concern should not be mistaken for evidence that an adjustment was or was not made in the trial; the detailed plan is not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a mixed-effects model result: a geometric least-squares mean ratio of 0.981 with a 90% confidence interval from 0.953 to 1.010. It does not report a p-value for this analysis. The same record provides group geometric means and geometric coefficients of variation, but those descriptive summaries are not a replacement for the model-based estimate.

An unadjusted recalculation from arm-level summaries, when presented, is a simple check based on posted summary statistics. It does not preserve the participant-level pairing of a crossover design and cannot reproduce a mixed-effects model that accounts for the design structure. Differences between such calculations and the sponsor’s result can therefore arise from the information used and the method, without either quantity representing the same estimand. The registry does not provide participant-level observations or sufficient model details to reproduce the sponsor analysis independently.

No discrepancy is flagged in the registry record. The sponsor’s model-based result is consequently the central inferential result to report, while any simple recalculation should be treated as a separate descriptive check rather than as an alternative sponsor analysis. The equivalence margins and full decision rule are not reported in the registry record, so the model result cannot by itself verify whether the prespecified criterion was met.

11. Multiplicity, Missing Data and Analysis Populations

The registry record defines the pharmacokinetic set as randomized participants who received at least 1 dose of zilucoplan and had at least 1 observable pharmacokinetic concentration measurement. It does not report how many participants met this definition, whether every randomized participant contributed to the primary analysis, or how many participants were excluded and for what reasons. The record gives enrollment as 14 and reports 14 participants in each treatment group, but these group counts do not establish the number with complete pharmacokinetic profiles or the number included in the model.

The primary endpoint requires concentration measurements over time and an estimate of exposure from predose to infinity. The sampling timeframe is stated as predefined time points through 816 hours (Day 35), but the handling of missing samples, incomplete profiles, concentrations below quantification limits, or profiles that could not support an estimate is not reported in the registry record. No imputation method, sensitivity analysis, or missing-data assumption is described.

The registry lists 7 outcome measures, including pharmacokinetic and safety measures, and reports 3 analyses. A multiplicity procedure, testing hierarchy, or explanation of how conclusions across the outcomes and analyses were controlled is not reported in the registry record. In general, multiplicity matters when several hypotheses are assessed because the chance of a false-positive finding can rise across a collection of tests. The record does not provide enough detail to determine whether or how this was addressed in the study’s analysis plan.

The endpoint is described as bioequivalence pharmacokinetics, but the equivalence limits and complete decision criteria are not reported. That omission prevents assessment of the formal pass-or-fail interpretation from the confidence interval alone. The protocol’s sample-size justification, interim-analysis plan, and full statistical analysis plan are also not reported in the registry record. Their absence should be treated as an information limitation, not as evidence that a particular procedure was absent from the trial.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s adverse-event summary lists 0 participants with serious events in the ZLP-PFS group and 0 in the ZLP-AI group. It also lists 0 deaths in each group. For other affected events, the summary lists 8 participants in each group, with 14 at risk in each. These are counts as posted in the registry record; no percentages need to be inferred to read them.

Zero observed serious events means that none were recorded among the participants represented in these group summaries during the reporting period. It does not establish that the risk of serious events is zero. With a small study population, uncommon events may not occur during observation even when they remain possible. The registry record does not list serious-event terms.

The record’s secondary outcomes include treatment-emergent adverse events, serious treatment-emergent adverse events, serious adverse device effects, and non-serious adverse device effects, assessed from Day 1 through the end-of-study or early-termination visit. The adverse summary uses a serious-events grouping and an “other” affected grouping; the record does not provide detailed event terms for the other category in the information. These counts should not be assumed to describe identical event types or to establish a comparative safety difference.

Safety interpretation is limited by the study’s size, duration, and the level of event detail reported. The registry record does not provide a narrative description of individual events, event severity beyond the stated groupings, or a statistical comparison of the safety outcomes.

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

The result describes pharmacokinetic exposure to zilucoplan after administration by prefilled syringe and autoinjector in healthy adult participants in a randomized crossover study. The primary estimate is a geometric least-squares mean ratio of 0.981, with a 90% confidence interval from 0.953 to 1.010. The estimate is close to 1, while the interval communicates uncertainty around that estimate. These numbers characterize the posted model result; they do not show that the treatments are exactly equal.

The study addresses a delivery-method comparison using area under the plasma concentration-time curve from predose to infinity. It does not compare zilucoplan with a different drug, placebo, or no treatment. It also does not directly establish performance in people with a medical condition, because the listed population is healthy adult participants. Generalizing beyond the studied population and study conditions requires evidence not reported in this registry record.

A formal bioequivalence conclusion depends on prespecified equivalence limits and a decision rule. Those limits and the full rule are not reported in the registry record. The confidence interval should therefore be read as an estimate of precision, not as a stand-alone determination that a formal criterion was satisfied. The record also does not provide all model details needed for independent reproduction of the sponsor analysis.

The safety summary reports no serious events or deaths in either treatment group, and 8 participants with other affected events in each group. These observations describe the posted counts in this study; they do not establish that either delivery method is safer or that serious events cannot occur. The record’s event detail is limited, and the study population was small.

In general, a clinical trial’s findings are bounded by its population, endpoint, design, measurement procedures, and duration of observation. Here, the evidence concerns a single-dose pharmacokinetic comparison in healthy adults under a crossover design. It does not answer questions about long-term use, clinical outcomes, or device performance in broader settings. Those topics are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates how a device comparison can be framed as a pharmacokinetic question. Rather than comparing different active ingredients, it compares zilucoplan administered by prefilled syringe with the same drug administered by autoinjector. The primary endpoint, area under the concentration-time curve from predose to infinity, summarizes overall exposure and is suited to assessing whether the delivery methods produce similar pharmacokinetic profiles.

The crossover structure is statistically important because each participant receives the compared treatments in different sequences. In general, within-person comparisons can reduce the influence of stable differences between participants. They also require attention to period, sequence, and carryover effects. The registry identifies the sequences but does not report how those effects were addressed in the model, making the distinction between the design description and the available analysis detail important.

The result also shows why a point estimate should not be interpreted alone. The reported ratio is accompanied by a 90% confidence interval, which conveys uncertainty. For equivalence, the interval must be interpreted against prespecified margins; the margins are not reported in the registry record. A value near 1 may be consistent with similar exposure, but the interval and decision rule together determine the formal statistical conclusion.

Finally, descriptive group summaries and a model-based comparison answer related but different questions. Geometric means and coefficients of variation describe the groups, while the mixed-effects model provides the reported inferential contrast. Understanding which quantity is being read, and what design information it uses, helps prevent a simple summary from being mistaken for the complete crossover analysis.

15. Limitations

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

The registry record contains the primary model estimate and confidence interval but does not give the equivalence margins or full decision rule. This limits the ability to verify a formal bioequivalence conclusion from the reported statistics alone. The mixed-effects model is named, but its terms, covariance structure, and treatment of period and sequence are not reported, so the model cannot be reproduced from the registry record.

The analysis population is defined, but its actual size and participant flow are not reported. The record does not describe missing concentration data, incomplete profiles, handling of below-quantification measurements, or sensitivity analyses. These details matter for an endpoint that requires estimating exposure through infinity from concentration observations collected over time.

The study is listed as open-label and single-center, with healthy adult participants and a single-dose comparison. These features limit how broadly the findings can be generalized. The registry record does not provide information about the washout interval, the full treatment-period schedule, laboratory blinding, or assay procedures. Those details should not be inferred from the stated crossover design or endpoint timeframe.

The enrollment is 14, and the treatment-group summaries each report 14 participants. This is a small study for assessing uncommon safety events. Although the registry reports no serious events or deaths, that observation cannot establish the absence of risk. The detailed terms for other affected events are not reported in the registry information.

The record lists multiple outcome measures and analyses, but a multiplicity strategy is not reported. The trial’s sample-size justification, interim-analysis plan, and full statistical analysis plan are also not reported in the registry record. These are limitations of the information available for interpretation; they do not show that a particular method was or was not used in the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate Zilucoplan Injected Subcutaneously Either by a Prefilled Syringe or an Auto-injector in Healthy Adult Participants — NCT06511076.
• Registry record last updated 2026-01-06; status last verified 2025-12.
• Results first posted 2026-01-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT06511076 is a completed, Phase 1, open-label, single-center, randomized, two-way crossover, single-dose study of zilucoplan administered by prefilled syringe or autoinjector in healthy adult participants. The registry records enrollment of 14, with treatment sequences A-B and B-A. The recorded start date is 2024-08-05 and primary completion date is 2024-11-26.

The primary endpoint was area under the plasma concentration-time curve from predose to infinity, assessed through predefined sampling time points up to 816 hours (Day 35). The reported mixed-effects model result is a geometric least-squares mean ratio of 0.981, with a 90% confidence interval from 0.953 to 1.010. Formal equivalence margins and the full analysis specification are not reported in the registry record.

The adverse summary lists no serious events or deaths in either group and 8 participants with other affected events in each group. The record identifies UCB Biopharma SRL as the sponsor and lists 7 outcome measures and 3 analyses.