Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy (NCT04025632), a randomized phase 2 study. The primary outcome is Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels.

2. Clinical Question

This is a question about a measured laboratory outcome over the main treatment period, not a complete assessment of every possible effect of treatment. The registry lists additional outcomes covering response criteria, mobility testing, muscle testing, activity assessments, function, and fatigue. Those measures provide other perspectives on change during the same period, but they do not replace the primary endpoint or establish a single overall conclusion. The clinical rationale for selecting serum CK as the primary measure is not reported in the registry record.

3. Trial Design

The study is registered as a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The registry describes quadruple masking, but does not identify which roles or groups were masked. Participants were assigned to zilucoplan 0.3 mg/kg or matching placebo, with a stated 1:1 allocation ratio. Both treatments were administered by daily subcutaneous injection during the 8-week main portion.

The registry lists an enrollment of 27, a start date of 2019-11-07, and a primary completion date of 2021-03-04. The overall status is terminated. The reason for termination, whether all planned follow-up was completed, and the details of any changes to the trial are not reported in the registry record. The dates and status alone do not explain why the study ended.

The primary outcome was percentage change from baseline to Week 8 in serum CK levels. Samples were collected before study drug administration at applicable visits, and CK was measured by a central laboratory. The primary population is specified as the ITT Population with no missing observations at Baseline and Week 8. The registry also lists secondary outcomes, including an ACR/EULAR response measure and changes in physical-performance, muscle-testing, activity, function, and fatigue measures.

Enrollment and the group sizes reported for individual outcomes are not interchangeable: outcome analyses may use only participants with the relevant measurements. The registry does not report the original sample-size justification, the planned statistical power for the trial, or the reason the study was terminated. Those details should not be inferred from the observed group sizes or the planning illustrations.

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: Of the 37 participants who were screened, 10 participants were deemed ineligible and were screen failures. 27 participants with immune-mediated necrotizing myopathy were randomized in a 1:1 ratio to receive zilucoplan 0.3 mg/kg or a matching placebo for the 8-week Treatment Period in the Main Portion of the study. All eligible participants were given the option to receive daily subcutaneous (SC) zilucoplan 0.3 mg/kg in the Extension Portion of the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT Population with no missing observations at Baseline and Week 8.

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: Intent-to-Treat (ITT) Population included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels, measured over Baseline (Day 1) and end of Main Portion (Week 8).

The primary endpoint is percentage change from baseline to Week 8 in serum creatine kinase, or CK, levels. The registry defines the measurement period as Baseline (Day 1) through the end of the Main Portion at Week 8. Blood samples were obtained before study drug administration at applicable visits, and a central laboratory measured CK. The primary population is described as the ITT Population with no missing observations at Baseline and Week 8.

As a general statistical description, a percentage-change endpoint expresses change relative to a baseline measurement, rather than reporting only the measurement at follow-up. It can therefore describe the direction and relative size of change over the defined period. The registry record does not give the precise calculation formula or a clinical threshold for interpreting a particular change. It also does not state why CK was selected over the other outcomes as the primary measure.

The reported arm summaries are means with standard deviations. The placebo group had a mean change of -20.72, with a standard deviation of 31.22, and the zilucoplan 0.3 mg/kg group had a mean change of -9.86, with a standard deviation of 26.06. These are summaries of the analyzed observations, not estimates adjusted for other variables. Their difference is not the sponsor’s primary inferential result: the sponsor reported a Van Elteren test using Wilcoxon-Mann-Whitney odds. The distinction matters because a comparison of means and a rank-based odds analysis summarize the outcome in different ways.

7. Results Posted in the Registry

• Zilucoplan 0.3 mg/kg: mean -9.86 versus -20.72 on control; difference 10.86 (95% CI -12.13 to 33.85), standardized effect d = 0.37; z-test p = 0.354.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants Who Achieve at Least Minimal Response Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Response Criteria Scale

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Zilucoplan 0.3 mg/kg: 54.5% (6/11) versus 50.0% (7/14) on control; risk difference 4.5 percentage points (95% CI -34.8 to 43.9), risk ratio 1.09 (0.51–2.31); unadjusted two-proportion z-test p = 0.821.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Zilucoplan 0.3 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Zilucoplan 0.3 mg/kg: mean -1.40 versus -0.71 on control; difference -0.69 (95% CI -2.87 to 1.50), standardized effect d = -0.28; z-test p = 0.537.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Zilucoplan 0.3 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Zilucoplan 0.3 mg/kg: mean 3.71 versus -0.18 on control; difference 3.89 (95% CI -6.17 to 13.95), standardized effect d = 0.30; z-test p = 0.449.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Zilucoplan 0.3 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary measures spanning response criteria, timed mobility, muscle testing, physician and patient activity assessments, function, extramuscular disease activity, and fatigue. Numerical results are available for several of these outcomes, and the observed summaries do not form a single consistent pattern of clear separation between the groups. The estimates are uncertain, with intervals that allow a range of comparative effects. Taken together, the secondary findings do not remove the uncertainty in the primary CK analysis or provide a precise, unified account of the comparative outcomes.

Secondary outcomes can help describe different aspects of a trial, but they are not interchangeable with the primary endpoint. They may also be less informative when estimates are based on limited observations or when many outcomes are examined. The registry does not report whether the secondary analyses were arranged in a prespecified hierarchy or whether their p-values were adjusted for multiplicity. Without that information, an unadjusted secondary p-value should not be treated as a stand-alone confirmatory result.

As a general statistical point, testing many outcomes creates more opportunities for apparently notable findings to arise by chance. Multiplicity procedures or a prespecified testing sequence can address that issue, but the registry record does not report such a strategy. The secondary results are therefore best read as supportive descriptions of measured outcomes, with attention to their estimates and uncertainty, rather than as separate proof of an overall effect. The primary result remains the central inferential comparison specified in the record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants Who Achieve at Least Minimal Response Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Response Criteria Scale
• Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time
• Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score
• Change From Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS) Score
• Change From Baseline to Week 8 in Patient Global Activity VAS Score
• Change From Baseline to Week 8 in HAQ Score
• Change From Baseline to Week 8 in MDAAT Extramuscular Disease Activity VAS Score
• Change From Baseline to Week 8 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score

9. Statistical Interpretation

10. Statistical Methods Explained

What does the sponsor’s primary test summarize?

The registry reports a 2-sided Van Elteren test, with the result expressed as Wilcoxon-Mann-Whitney odds. As a general statistical explanation, rank-based methods compare the ordering of observations between groups rather than relying only on the difference between arithmetic means. The Van Elteren approach is a stratified form of rank comparison. The registry record does not identify any stratification factors, so no particular adjustment or grouping scheme should be assumed. The reported odds estimate and its confidence interval summarize that sponsor analysis; they should not be interpreted as a mean difference.

A 2-sided test considers departures in either direction. A p-value summarizes how unusual the observed data, or data more extreme under the test, would be under the test’s null model. It does not give the probability that the null hypothesis is true. For the primary endpoint, the sponsor-reported p-value is 0.464. That value alone does not quantify the range of effects compatible with the data, which is why the estimate and confidence interval also matter.

What is the recalculated mean comparison?

The simple recalculation uses the posted arm means, standard deviations, and sample sizes to express the unadjusted difference in group means. The comparison is zilucoplan minus placebo. It yields a mean difference of 10.86, with a 95% confidence interval from -12.13 to 33.85 and an unadjusted p-value of 0.354. This is a calculation from summary statistics, not the sponsor’s primary test. It does not reproduce the Van Elteren analysis and should not be presented as if the sponsor had reported it.

As a general statistical point, a mean-based analysis describes differences in averages, whereas a rank-based analysis uses the ordering of observations. These methods can yield different estimates and p-values without either calculation being an arithmetic error; they address the data through different summaries and assumptions. The registry does not flag a discrepancy between the sponsor result and the recalculation. The recalculated result remains supplementary context, while the sponsor’s reported analysis is the trial’s primary inferential result.

How should the other model-based results be read?

Some secondary continuous outcomes are reported using a Linear Mixed Effect Model and least-squares mean differences. In general, a mixed-effects model can account for relationships among repeated measurements and can estimate group contrasts within a model. The registry record does not fully describe the model specification, included covariates, covariance structure, or handling of missing measurements. It would therefore be inappropriate to reconstruct those choices from the result alone. The outcome summaries include standard errors for the arm estimates, which describe uncertainty in those estimates rather than the spread of individual observations.

For the binary response outcome, the sponsor reports logistic regression and an odds ratio. In general, logistic regression models the odds of a binary outcome, and an odds ratio compares those odds between groups. The registry does not provide enough model detail to determine all adjustments used. The reported odds ratio is not the same quantity as a risk difference or a ratio of probabilities, so it should not be treated as interchangeable with those measures.

What do the confidence intervals and p-values contribute?

As a general statistical explanation, a confidence interval describes a range of estimates compatible with the observed data under the method’s assumptions. It conveys uncertainty in the estimate, not the range in which every individual response falls. The primary sponsor interval is on the Wilcoxon-Mann-Whitney odds scale; the recalculated interval is on the mean-difference scale. Their numerical values cannot be compared as though they were the same effect measure.

A p-value and a confidence interval are related but answer different presentation needs: a p-value gives a test-based summary, while an interval displays a set of plausible effect values at the stated confidence level. Neither resolves design limitations, missing-data questions, or the clinical importance of an effect. A clinical threshold for meaningful change is not reported in the registry record.

What is not specified about the statistical plan?

The registry record does not report the original sample-size justification, a full statistical analysis plan, interim analyses, or a multiplicity strategy. It also does not give enough information to describe all analysis-model details or the handling of missing data for every outcome. General statistical considerations cannot fill those gaps. The planning illustrations are separate calculations based on the observed effects, not evidence of the design assumptions used by the trial team.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an effect estimate. The sponsor’s primary odds estimate is 0.55, with a 95% confidence interval from 0.19 to 1.57. Because the interval spans values on either side of the null for an odds comparison, the data do not pin down the comparative result closely. The interval includes the possibility of effects in different directions on that scale, and it covers a wide range of magnitudes.

The unadjusted mean-difference recalculation is 10.86, with a 95% confidence interval from -12.13 to 33.85. This interval crosses zero and extends from a negative to a positive mean difference. Its width indicates that the summary data are compatible with materially different mean comparisons. The sponsor’s interval and this recalculated interval concern different measures, so their widths should not be compared directly as a contest between methods.

Confidence intervals are not ranges containing a stated proportion of individual participants’ outcomes. As a general explanation, a confidence interval reflects uncertainty in an estimated group-level quantity under the analysis assumptions. It does not address every source of uncertainty, including potential bias, missing measurements, or the choice of outcome. The registry does not provide participant-level data or a clinical threshold that would permit a more detailed assessment of precision or clinical importance.

The relatively small analyzed groups for the primary outcome are part of the context for the broad intervals, but the exact contribution of sample size versus outcome variability cannot be separated from these summaries alone. The standard deviations reported for the arm means also show that observations vary within groups. The appropriate reading is that the estimate is uncertain, not that the true effect must be exactly at the point estimate or at any particular endpoint of the interval.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations express the number of participants per arm for the continuous and binary outcomes shown. They are not totals across arms or total event counts. The record’s planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses an effect equal to the stated fraction of the observed effect. No time-to-event outcome is included in these comparisons; the registry’s general note that time-to-event calculations use total events does not change the per-arm interpretation of these figures.

The 80% power column gives the illustrative number of participants per arm needed for an analysis to have an 80% chance of detecting the assumed effect under the stated calculation assumptions, if that effect and those assumptions were correct. The 90% power column describes the corresponding planning target with a higher chance of detecting that assumed effect. These are design-planning quantities, not guarantees about what a future study would find.

The rows that plan for 100%, 75%, or 50% of the observed effect show how the required group size changes when the target effect is smaller than the observed estimate. A smaller effect is harder to distinguish from random variation, so the illustration requires more participants per arm for the same power target. The observed effects are uncertain estimates from this trial, and the registry does not report that these illustrations were used to design the original study.

This is not observed power. It is a planning illustration using the observed effect as an input, not a retrospective measure of whether the trial had adequate power or a probability that its result is true. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 10.860; pooled standard deviation σ = 29.219.
2. n = 2 × (1.96 + 0.842)² × 29.219² / 10.860² = 113.6, rounded up to 114 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 10.86                      # observed difference in means
sigma <- 29.2194374906966                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4025632)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 114 (80% power), 153 (90% power)
 75% of observed effect: n per arm = 203 (80% power), 271 (90% power)
 50% of observed effect: n per arm = 455 (80% power), 609 (90% power)
power.t.test: 114.6 
Simulated power at n = 114 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

For the primary endpoint, the sponsor’s reported analysis is a 2-sided Van Elteren test expressed as Wilcoxon-Mann-Whitney odds. It gives an estimate of 0.55, a 95% confidence interval from 0.19 to 1.57, and a p-value of 0.464. That is the trial’s own reported primary comparison and should remain distinct from a recalculation based on arm means and standard deviations.

The unadjusted recalculation gives a mean difference of 10.86, a 95% confidence interval from -12.13 to 33.85, and a p-value of 0.354. It is useful as a separate summary-statistics comparison, but it estimates a difference in means rather than the sponsor’s rank-based odds. The two analyses therefore are not competing versions of the same calculation.

The registry does not flag a discrepancy. The sponsor’s method takes precedence if a discrepancy is flagged; in this record, the distinction is instead that the analyses use different measures and methods. The recalculation should not replace the sponsor’s analysis or be described as a correction. Both results indicate considerable uncertainty, but the sponsor-reported result is the appropriate reference for what the trial’s own primary analysis found.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or a prespecified method for controlling the chance of false-positive findings across outcomes. This absence matters particularly when interpreting unadjusted p-values for secondary comparisons: each p-value is a result for its own comparison, and the record does not establish that the collection of tests was controlled as a family.

The primary endpoint population is described as the ITT Population with no missing observations at Baseline and Week 8. That definition identifies who contributed to the reported primary endpoint summary; it does not describe how missing observations were handled for other outcomes. The registry record does not report imputation methods, sensitivity analyses for missing data, or the amount and reasons for missing measurements across outcomes. Those methods should not be inferred from the phrase used to define the primary population.

The record reports an enrollment of 27, while the analyzed group sizes differ by outcome. That variation is consistent with outcome-specific analysis populations, but the registry does not provide a full accounting of participant flow or explain each difference in available observations. Group sizes in individual analyses should therefore be read as the numbers contributing to those reported outcomes, not as a complete account of enrollment, follow-up, or trial completion.

The registry does not report interim analyses, stopping rules, a full statistical analysis plan, or the original sample-size justification. The terminated status is recorded, but the reason for termination is not reported in the registry record. These omissions limit assessment of how analysis decisions were prespecified and how missing data, multiplicity, and trial conduct were handled. They do not establish that any particular procedure was or was not used outside the information recorded.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (12.0%), ventricular tachycardia (6.7%), rhinovirus infection (6.7%), urinary tract infection (6.7%), liver function test increased (6.7%).

Safety summaries are reported separately for the Main Portion and Extension Portion. In the Main Portion placebo group, serious adverse events affected 3 of 15 participants at risk; in the zilucoplan 0.3 mg/kg group, serious adverse events affected 0 of 12 participants at risk. The Extension Portion zilucoplan group reports 8 of 25 participants at risk with serious adverse events and 1 death. The Main Portion groups each report zero deaths.

These are descriptive counts for the stated periods and groups. The extension group is not directly comparable with either Main Portion group from these figures alone: the periods and group descriptions differ, and the registry record does not provide the information needed to standardize exposure or explain the extension population. A count of participants with an event is also not a measure of how long participants were observed.

The listed serious-event terms include COVID-19 at 12.0%, and Ventricular tachycardia, Rhinovirus infection, Urinary tract infection, Liver function test increased, and Hypoxia at 6.7% each. The denominator and counting convention for those term percentages are not reported in the registry record, so they should be read as listed rather than converted into participant counts. These summaries do not establish causality or permit a complete comparison of safety between treatment groups.

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

The posted primary result is an estimate with substantial uncertainty. The sponsor’s rank-based analysis reports a Wilcoxon-Mann-Whitney odds estimate of 0.55, with a 95% confidence interval from 0.19 to 1.57 and a p-value of 0.464. The unadjusted mean comparison also has an interval that crosses zero. These results do not precisely establish the size or direction of a comparative effect on the primary endpoint.

That interpretation is not the same as saying that the groups were equivalent or that there was no effect. A failure to obtain a narrowly informative estimate does not show that all clinically meaningful differences have been excluded. The registry does not report a clinical threshold for meaningful change in CK, so statistical estimates cannot be translated into a judgment about clinical importance from this record alone.

The secondary measures cover several domains, but their results are also limited by uncertainty and the absence of a reported multiplicity strategy. They should not be combined informally into a single claim. The safety summaries describe events in the listed study portions, but do not by themselves demonstrate that an event was caused by study treatment or provide a complete comparative safety assessment.

The trial is Phase 2 and terminated. The record does not state why it was terminated, so that status cannot be used to infer a particular efficacy or safety conclusion. Taken together, the registry results describe a small study with imprecise estimates and incomplete reporting of some design and analysis details. They are informative as a record of the measurements and analyses reported, but they do not settle the treatment’s clinical effect.

18. Why This Trial Matters Statistically

This trial illustrates why an estimate, its uncertainty, and the analysis method all matter. The sponsor’s primary result is a rank-based odds estimate, while a summary-statistics recalculation gives a mean difference. Those quantities answer related but distinct questions. Reporting them separately prevents a recalculated mean comparison from being mistaken for the trial’s own primary analysis.

The confidence intervals also show why a p-value alone is not enough. The primary interval spans a wide range on the sponsor’s odds scale, and the recalculated mean interval extends across zero. A reader can see that the data do not locate the comparative effect precisely, even without treating a thresholded p-value as a complete summary.

The secondary outcomes and safety summaries demonstrate additional interpretation challenges. Different outcomes have different scales and analysis populations, and the record does not report a multiplicity strategy or full missing-data methods. The terminated status adds context, while the absence of a reported reason cautions against attaching an explanation to it. These are practical statistical issues in reading trial records: distinguish the planned primary question from exploratory outcomes, separate sponsor analyses from recalculations, and avoid claiming more precision than the intervals support.

Finally, the sample-size illustrations are planning tools based on observed effects, not evidence of the original design’s adequacy. Their value is to show how assumptions about the target effect and power affect planning, while keeping those hypothetical calculations separate from the observed trial findings.

19. Limitations

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

The primary outcome analysis is based on the ITT Population with no missing observations at Baseline and Week 8, and the reported group sizes are limited. The registry does not give a participant-flow account explaining how those analysis groups relate to enrollment or why outcome-specific group sizes differ. It also does not report participant-level measurements, which limits assessment of outliers, distributions, or sensitivity to individual observations.

The sponsor’s primary analysis is reported as a Van Elteren test, but the registry does not specify the stratification factors or provide a full statistical analysis plan. The summary-statistics recalculation is unadjusted and uses a different effect measure, so it cannot reproduce all aspects of the sponsor analysis. The model details for reported secondary analyses are also incomplete in the registry record.

The record does not report the original sample-size justification, a multiplicity plan, interim analyses, missing-data methods across outcomes, or the reason for termination. The clinical threshold for interpreting the primary CK change is not reported either. These gaps limit conclusions about design intent, analysis choices, clinical importance, and the context of trial completion.

The safety information separates the Main Portion from the Extension Portion, and the available group summaries do not supply exposure-adjusted comparisons or full detail on event timing and attribution. Term-specific percentages are listed without a reported denominator definition. Therefore, the safety summaries are descriptive and should not be treated as a complete causal comparison between groups or periods.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy — NCT04025632.
• Registry record last updated 2022-07-27; status last verified 2022-07.
• Results first posted 2022-05-16.
• 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.

23. Record Summary

NCT04025632 is a terminated Phase 2, randomized, double-blind, placebo-controlled study of zilucoplan in immune-mediated necrotizing myopathy. Participants were assigned to daily subcutaneous zilucoplan 0.3 mg/kg or matching placebo for an 8-week main portion. The registry reports an enrollment of 27.

The primary endpoint was percentage change from baseline to Week 8 in serum CK. The sponsor reported a 2-sided Van Elteren test with Wilcoxon-Mann-Whitney odds of 0.55, a 95% confidence interval from 0.19 to 1.57, and a p-value of 0.464. An unadjusted mean-difference recalculation is 10.86, with a 95% confidence interval from -12.13 to 33.85. The two results use different methods and effect measures.

Secondary outcomes and safety summaries add context but do not remove uncertainty in the primary result. The original sample-size justification, multiplicity strategy, detailed missing-data methods, and reason for termination are not reported in the registry record.