Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG (NCT03304054), a randomized phase 3 study. The primary outcome is Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results.

2. Clinical Question

The registry lists enrollment of 93. That enrollment figure does not establish the number included in the primary analysis: the analysis population required both receipt of study medication and a post-treatment efficacy assessment. The number analyzed in each group is not reported in the registry record.

3. Trial Design

The registry describes a Phase 3, randomized, quadruple-masked, parallel-group study comparing amifampridine phosphate with placebo. Its official title identifies patients with MuSK antibody-positive myasthenia gravis as the principal focus and also describes a sample of patients with AChR antibody-positive myasthenia gravis. The condition listed is generalized myasthenia gravis. The record lists enrollment of 93.

The study started on 2018-04-18, had a primary completion date of 2020-01-31, and is marked completed. The registry identifies Catalyst Pharmaceuticals, Inc. as sponsor. It does not report the treatment allocation ratio, the randomization sequence method, or which specific parties were masked. The arm descriptions contain no additional details about the tablets or treatment procedures.

The primary outcome is an MG-ADL score, measured at the last day of the run-in period and at a post-treatment visit. The listed post-treatment assessment was on day 10, or at an earlier time point if a patient discontinued treatment early. The registry describes the primary analysis as based on a Full Analysis Set that included randomized patients who received at least one dose after randomization and had at least one post-treatment efficacy assessment. The number of patients meeting those criteria is not reported in the registry record.

These design details establish that the study was intended to make a randomized comparison involving active treatment and placebo. They do not, by themselves, establish the treatment effect. The outcome values, group-specific changes, and primary test result are not reported in the registry record. Further protocol details, including the study’s allocation procedures and the rationale for the enrollment target, are also not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A screening visit was conducted to ensure that each patient met inclusion/exclusion criteria. Those patients successfully completing screening had procedures/assessments conducted at the start of the Run-in period (Day 1, before starting study medication) and during run-in, until stable dose and frequency of amifampridine is established for at least 7 days, and at least a 2-point improvement in MG-ADL score was achieved from the start of Run-in to be eligible for randomization (Day 0).

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis of primary outcome data was based on the Full Analysis Set population, which included all randomized patients who received at least one dose of study medication (amifampridine or placebo post randomization) and had at least one post-treatment efficacy assessment. Patients who discontinued with no post-randomization data (no Day 0 and no Day 10 data) were excluded from all efficacy analyses but were included in the safety analyses.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The analysis of baseline characteristics included all patients in the Safety population, who are those patients who enrolled and received at least one dose of amifampridine. Patients who began the run-in period belong to the Safety population whether they were randomized to treatment or not.

6. Primary Endpoint

The registry lists the primary outcome as Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results, measured over Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time point at which a patient discontinued treatment early)..

The primary endpoint is change from baseline in the Myasthenia Gravis–Activities of Daily Living score, or MG-ADL. The baseline assessment was taken on the last day of the run-in period, identified as Day 0. The post-treatment assessment was planned for Day 10, although a result from an earlier time point could be used if a patient discontinued treatment early.

MG-ADL is a patient-reported measure of myasthenia gravis symptoms and functional performance in activities of daily living. It has eight items, each scored from 0 to 3. A score of 0 indicates no symptoms or impairment for an item; a score of 3 indicates the most severe symptoms or impaired performance. The total is the sum of item scores, with a minimum of 0 and a maximum of 24. Higher total scores therefore represent more symptoms or impairment on this scale.

General statistical context: repeated assessment of a patient-reported functional scale can describe whether reported symptoms and everyday function change during the treatment period. A change-from-baseline outcome focuses the comparison on movement from each patient’s starting score rather than only on the post-treatment score. The registry specifies the measure and assessment timing, but does not report the numerical change summaries or a numerical treatment comparison. The precise clinical importance of any observed change cannot be determined from the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as continuous and gives its descriptive parameter as the mean, with standard deviation as the measure of dispersion. It also names the Wilcoxon–Mann–Whitney rank-sum test for equality of change-from-baseline distributions. These parts of the analysis have different roles: means and standard deviations describe the observed values, while the rank-sum test evaluates a distributional comparison. Numerical summaries and test results are not reported in the registry record.

What does a mean and standard deviation describe?

General statistical context: the mean is a measure of the center of a set of values. The standard deviation describes how dispersed individual values are around that center. Together they can help characterize a continuous outcome, but they do not show the shape of the full distribution. Two groups can have similar means while differing in other distributional features, and a mean alone does not indicate how much individual patients’ scores vary.

For MG-ADL, the registry specifies that the change from baseline was assessed. A change score represents movement between the baseline assessment and the post-treatment assessment. The registry permits the post-treatment result to come from an earlier visit when treatment was discontinued early. That timing rule is relevant when interpreting any change summary because the follow-up interval may differ across patients. The record does not provide the actual timing distribution or explain how the earlier assessments were incorporated beyond describing them as eligible post-treatment results.

What does the rank-sum test assess?

General statistical context: the Wilcoxon–Mann–Whitney rank-sum test places observations from the groups into a combined ordering and assesses whether values in one group tend to rank differently from values in the other. It can be useful when the analysis concerns distributions and does not depend on treating the mean as the sole feature of interest. It should not automatically be interpreted as a test of medians; that interpretation requires additional assumptions about the distributions being compared.

The registry wording specifies a test of equality of change-from-baseline distributions. This means the stated test concerns the change scores, rather than simply comparing the baseline scores or post-treatment scores alone. However, the description ends before fully naming the diagnostic groups in the comparison. It also does not fully clarify how that comparison corresponds to randomized treatment assignment. The precise estimand—the particular group contrast and outcome quantity the analysis aims to estimate—is therefore not completely clear from the available wording.

Why can distributional shape matter?

General statistical context: continuous clinical scores can be unevenly distributed, can include many similar values, or can have extreme observations. A rank-based procedure uses ordering rather than relying directly on the numerical distance between every pair of values. This can make it less dependent on some assumptions about the shape of the data, but it does not make an analysis assumption-free. Independence of observations and a clearly defined comparison remain important. Interpretation can also be affected when groups have differently shaped distributions.

The registry does not report diagnostic checks, model assumptions, handling of ties, or a detailed statistical analysis plan. These details are not reported in the registry record and should not be filled in by inference from the test name.

How should uncertainty be assessed?

General statistical context: a confidence interval gives a range of values compatible with the observed data under a specified estimation procedure and its assumptions. Its width conveys precision: wider intervals indicate more uncertainty about the effect size. A p-value and a confidence interval answer related but different questions. A small p-value alone would not indicate whether a difference is large enough to matter clinically, while a confidence interval helps show which effect sizes remain plausible.

No primary confidence interval, test statistic, p-value, or numerical effect estimate is reported in the registry record. Thus, neither statistical significance nor precision can be assessed from the primary outcome details alone. The descriptive label “mean” and “standard deviation” does not supply the missing values.

What do the planning assumptions mean?

General statistical context: the record describes a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also says that the target effect is expressed as a stated fraction of the observed effect. Such figures are illustrations of sample sizes under those assumptions; they are not observed treatment effects and are not observed power. The record does not provide a trial-specific design justification or indicate that those assumptions were the original protocol’s planning basis. No planning sample-size values should be interpreted as evidence about the study’s outcome.

For continuous outcomes, a planning calculation can be sensitive to the chosen effect size and assumptions about variability. General statistical context: over-dispersion means that variation is greater than a model expects; if present and not accounted for, uncertainty estimates from that model may be too small. The registry does not report whether over-dispersion was assessed or relevant to this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses. The primary outcome is MG-ADL change, and the listed secondary outcome concerns QMG total scores by time point and myasthenia gravis type, with rank-sum test results. The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for controlling the chance of false-positive findings across multiple tests. These details are not reported in the registry record. Without them, the relationship between any individual test result and an overall confirmatory claim cannot be assessed; in any case, numerical results are not reported for the primary comparison.

The registry describes the primary analysis population as randomized patients who received at least one dose of study medication after randomization and had at least one post-treatment efficacy assessment. The description begins to state an additional condition for patients who discontinued, but the wording is incomplete. The full analysis-population definition, the number analyzed in each group, and reasons for exclusion are not reported in the registry record.

Missing outcome data matter because the primary endpoint requires a baseline and post-treatment assessment. The registry allows an earlier post-treatment assessment for patients who discontinued treatment early. It does not report how missing baseline or post-treatment scores were handled, whether any imputation was used, or whether sensitivity analyses examined alternative assumptions about missing outcomes. The extent and pattern of missingness are also not reported in the registry record.

General statistical context: restricting an analysis to patients with a post-treatment assessment can affect interpretation if the availability of that assessment is related to symptoms, treatment response, or tolerability. This does not establish that such a bias occurred in this study. It identifies why the analysis-population rule and missing-data handling are important to understand. The incomplete population wording and absence of missing-data details limit assessment of how the analyzed patients represent the randomized groups.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myasthenia gravis (1.2%), myasthenia gravis crisis (1.2%).

The registry lists serious adverse event figures for the amifampridine phosphate and placebo groups. The numbers described as at risk are 86 for amifampridine phosphate and 36 for placebo. The corresponding numbers affected by serious adverse events are 2 and 0. The registry lists 0 deaths in both groups. It also lists other adverse event figures of 80 for amifampridine phosphate and 7 for placebo.

The serious adverse event terms shown include “Myasthenia gravis” at 1.2% and “Myasthenia gravis crisis” at 1.2%. These are registry-listed percentages, not new calculations. The record does not provide enough detail in these figures to establish the duration of exposure or explain how adverse-event terms were coded. The numbers at risk differ between the two groups, and the registry does not provide an explanation for that difference.

The line labeled Overall repeats the amifampridine phosphate figures rather than presenting values that combine the two listed groups. It should not be read as a pooled total. Serious events, other adverse events, and deaths are distinct summaries, and the figures should not be combined into a single measure. The registry does not provide comparative statistical tests or uncertainty intervals for these safety figures. They describe reported counts and listed percentages; they do not establish a causal relationship or quantify a comparative safety effect.

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

The registry record establishes that a randomized, placebo-controlled, parallel-group study of amifampridine phosphate was conducted in the context of generalized myasthenia gravis, with MuSK antibody-positive disease as its focus and a sample of AChR antibody-positive patients also named in the official title. It specifies an MG-ADL change outcome, its assessment schedule, and a rank-sum test for comparing change distributions. Those details describe the intended measurement and analysis, not the observed result.

The record does not report the numerical primary outcome comparison. Without group-specific changes, an effect estimate, or a test result, it is not possible to characterize the direction or size of the primary finding. Without an uncertainty interval, its precision cannot be judged. The outcome description is also incomplete at the point where it identifies the diagnostic groups being compared, so the precise contrast is not fully clear from the registry wording.

General statistical context: even when a trial is randomized, interpretation depends on knowing what comparison was analyzed, who was included, how missing outcomes were handled, and how uncertainty was quantified. Randomization supports a fair comparison when preserved through conduct and analysis, but the label “randomized” alone does not resolve questions about exclusions, incomplete follow-up, or outcome reporting. The record does not contain enough details to evaluate those issues fully.

The safety entries report events in the two named treatment groups, including serious adverse event figures and deaths. They are descriptive counts, with group-specific numbers at risk that differ. These figures do not supply a complete comparison of risks over a common exposure period, and no comparative uncertainty estimates are reported. They should not be treated as evidence of a particular causal effect.

Accordingly, the record supports a description of the trial design, endpoint, named statistical test, and certain safety summaries. It does not support a conclusion about the size, precision, or statistical significance of the primary outcome comparison. No clinical recommendation or claim about treatment benefit follows from the information reported in this registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its stated primary outcome is a patient-reported functional score, while the named primary analysis is a rank-based comparison of change distributions. Keeping the endpoint and the test’s target in view helps avoid treating a rank-sum result as if it were automatically a comparison of mean changes. The registry reports means and standard deviations as descriptive summaries, but does not include their numerical values or the test result.

The official title identifies MuSK antibody-positive myasthenia gravis and a sample of AChR antibody-positive patients. The primary outcome title also organizes results by myasthenia gravis type. That structure makes the precise contrast particularly important: an interpretation depends on whether the comparison is between randomized treatment groups, disease types, or a combination of both. The available primary-outcome wording does not fully identify the groups at the end of its description.

The assessment schedule is another relevant statistical detail. Baseline is the last day of the run-in period, while post-treatment assessment is planned for Day 10 or may occur earlier after early treatment discontinuation. This creates a need to understand how different assessment timing and missing data were handled. Those details are not reported in the registry record.

Finally, the reported analysis population requires treatment exposure and a post-treatment assessment, but the complete population definition is not available. The number analyzed and the handling of missing outcomes are also absent. These are not minor interpretive details: they help define what population the outcome comparison represents and how robust it may be. The registry’s design information is useful, but the missing numerical outcome results and analysis details prevent a full statistical appraisal of the primary finding.

14. Limitations

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

The main limitation is that the registry record does not report numerical primary outcome results. It contains no group-specific MG-ADL changes, effect estimate, test statistic, p-value, or confidence interval. As a result, neither the direction nor the magnitude and precision of the primary comparison can be evaluated from the record.

The primary outcome description is incomplete at the point where it identifies the subjects whose change distributions are compared. Although the study title names active treatment and placebo and identifies different myasthenia gravis types, the record wording does not fully resolve whether the stated primary test is a treatment contrast, a disease-type contrast, or another comparison. That ambiguity limits interpretation of the estimand.

The registry describes the analysis population as randomized patients who received at least one dose and had at least one post-treatment assessment, but the rest of the population description is incomplete. Group-specific analysis counts and reasons for exclusion are not reported in the registry record. The method for handling missing outcome data and any sensitivity analyses are also not reported. Earlier post-treatment results could be used after early discontinuation, but the effect of varying assessment times cannot be assessed.

Other details that would aid appraisal are not reported in the registry record, including the allocation ratio, randomization procedure, masking roles, treatment regimen, and a trial-specific statistical analysis plan. The arm descriptions contain no further treatment details. The planning illustration is not a substitute for the trial’s design justification or observed results.

The safety entries have unequal numbers at risk between the named groups, and the overall row repeats the amifampridine phosphate values. The registry does not explain these features in the listed figures. They warrant careful reading rather than unreported assumptions about denominators, exposure, or pooled totals.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG — NCT03304054.
• Registry record last updated 2024-03-12; status last verified 2021-07.
• Results first posted 2021-08-13.
• 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.

18. Record Summary

The registry lists NCT03304054 as a completed Phase 3 randomized, quadruple-masked, parallel-group study of amifampridine phosphate and placebo in generalized myasthenia gravis. The official title focuses on MuSK antibody-positive disease and includes a sample of AChR antibody-positive patients. Enrollment is listed as 93. The study started on 2018-04-18 and its primary completion date is 2020-01-31.

The primary outcome is change in MG-ADL score from the run-in baseline to a post-treatment visit, planned for Day 10 or an earlier time point after early discontinuation. The registry names a Wilcoxon–Mann–Whitney rank-sum test. It also lists QMG as a secondary outcome. The numerical primary outcome comparison and full analysis details are not reported in the registry record.

The record includes serious adverse event and other adverse event figures, along with zero deaths listed in each group. These are descriptive entries and do not replace the missing primary efficacy results. The precise primary contrast, missing-data methods, multiplicity plan, and trial-specific design justification are not reported in the registry record.