Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NCT04145440), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The clinical question combines safety monitoring with a broader assessment of MOR202 in anti-PLA2R antibody positive membranous nephropathy. The registry describes newly diagnosed or relapsed participants in Cohort 1 and participants with refractory disease in Cohort 2. Both cohorts received the same study drug, with the same cycle schedule described in the record.

The study was open-label, non-randomized, and single-group. It therefore does not establish a randomized comparison between MOR202 and another treatment or a control. Differences in the participants’ disease status also mean the cohorts should not be treated as interchangeable comparison groups. The primary outcome focused on adverse events during treatment. Secondary outcomes included immunological response, anti-felzartamab antibodies, serum concentrations, and adverse events during follow-up. The registry record does not report a primary efficacy endpoint or a control-group estimate.

3. Trial Design

This was a Phase Ib/IIa, open-label, multicenter clinical trial of MOR202 in adults with anti-PLA2R antibody positive membranous nephropathy. The study began on 2019-10-15, had a primary completion date of 2022-01-19, and is listed as completed. Enrollment was 31 participants. The allocation was non-randomized, masking was absent, and the model was single-group.

The record describes two disease-status cohorts. Cohort 1 included newly diagnosed or relapsed participants; Cohort 2 included participants whose membranous nephropathy was refractory to immunosuppressive treatment. Both received MOR202 by intravenous infusion over 6 treatment cycles of 28-days each. Dosing occurred weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6. These are distinct clinical cohorts, not randomized treatment arms or control groups.

The primary endpoint was the number of participants with adverse events from Week 1 to Week 24. The Safety Analysis Set included participants who received at least one dose of study drug. The adverse-event record also gives separate counts for serious and other adverse events during the treatment period, Weeks 1-24, and follow-up period, Weeks 25-52. Secondary outcomes addressed immunological response, anti-felzartamab antibodies, serum concentrations, and adverse events during follow-up.

The registry record does not report the statistical analysis plan, a sample-size justification, or interim analyses. With no randomization or control group, the design is primarily informative about observed safety and response within the treated cohorts; it cannot isolate a causal treatment effect from other explanations for observed outcomes.

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 total of 65 participants were screened for this study. 31 participants were enrolled and received at least one dose of study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set included all participants who received at least one dose of study drug.

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 Full Analysis Set (FAS) included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over Week 1 to Week 24.

The primary endpoint was the number of participants with adverse events from Week 1 to Week 24. An adverse event was defined as any untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship was considered possible. This definition means the endpoint counts events among treated participants without requiring the event to be judged treatment-related.

The endpoint is used to describe safety during the specified treatment period. Counting participants, rather than counting every episode, expresses how many people experienced an adverse event; it does not by itself describe how many events each participant had, their duration, severity, or clinical consequences. The registry’s separate description of serious adverse events includes events meeting specified criteria, such as death, a life-threatening event, hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event requiring intervention to prevent such outcomes.

The primary analysis population was the Safety Analysis Set: participants who received at least one dose of study drug. The registry reports serious and other adverse-event counts by cohort and period, but it does not report a combined count of participants with any adverse event for the primary endpoint. Nor does the record provide an estimate comparing MOR202 with a control treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count tell the reader?

A count of participants with an event describes how many people in an analysis population experienced that event during a stated period. It differs from an event count: a participant may experience more than one event, while a participant count records that person within the relevant category. Counts are easiest to interpret alongside the number of participants at risk and a clear definition of the event and observation period. The registry gives those counts for serious and other adverse events, by cohort and period.

The primary endpoint is also a participant count. Its definition covers any untoward medical occurrence after receipt of study drug, regardless of possible causal relationship. That broad definition is useful for safety surveillance because it does not omit an event simply because investigators do not consider the study drug a possible cause. At the same time, it means the count alone cannot show whether the drug caused an event. Attribution, event severity, timing, and clinical context are separate considerations.

Why distinguish serious events from other events?

Seriousness is a classification based on consequences or medical importance, not a judgment about causation. The registry definition includes death, life-threatening events, hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, and certain important medical events requiring intervention to prevent listed outcomes. Other adverse events are presented separately from serious adverse events. A reader should therefore keep the event category distinct from any claim that treatment caused it.

The registry lists serious adverse-event terms with percentages, but does not report the denominator or additional context for those values. Without that context, the percentages should not be used to reconstruct participant counts or to compare event occurrence across groups. The record also does not describe whether a participant with more than one serious event could contribute to more than one listed term.

What can a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate by giving a range of values compatible with the data under the method’s assumptions. Wider intervals indicate less precision; narrower intervals indicate greater precision. An interval does not remove bias or turn a non-randomized comparison into a randomized one. The registry record does not list inferential analyses or confidence intervals for the adverse-event results, so no interval-based precision assessment is reported for these counts.

Why does the study design matter for interpretation?

Random allocation, when used, can support a fair comparison by balancing prognostic factors on average across treatment groups. This study was non-randomized and single-group, with two cohorts defined by disease status. There was no randomized control group, and the cohorts were not like-for-like controls. Therefore, differences in their event counts cannot be attributed to MOR202 or interpreted as a comparative treatment effect. Open-label conduct also means masking was absent; the record does not describe further measures to address possible effects of awareness on event reporting or assessment.

How should the planning illustrations be read?

General sample-size planning asks how many participants would be needed to detect a specified effect under chosen assumptions. The registry’s stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated method concerns a total number of events; for other outcomes, it concerns participants per arm. These are planning illustrations, not the trial’s observed enrollment target or observed power.

The assumptions do not change the trial’s actual design. This study was non-randomized and single-group, and the record cautions that its cohorts are not a like-for-like control comparison. Thus, hypothetical two-arm planning values should not be mistaken for evidence that the study was designed or conducted as a randomized comparison. The registry record does not report the trial’s own sample-size justification or statistical analysis plan.

Over-dispersion is a general statistical concern when variability in observed counts exceeds what a model assumes. If present and ignored, estimated uncertainty can be too small and statistical conclusions too confident. The registry record does not report an over-dispersion assessment or a model for these adverse-event counts. This matters because the posted results are descriptive counts, not a model-based comparative analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1 (Newly Diagnosed or Relapsed Participants", "Cohort 2 (Refractory Participants)")
n      <- c(18, 13)
events <- c(15, 12)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1 (Newly Diagnosed or Relapsed Participants  18  15  83.3  58.6  96.4  60.8  94.2  60.4  93.9
ARM  Cohort 2 (Refractory Participants)  13  12  92.3  64.0  99.8  66.7  98.6  66.1  98.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and identifies several secondary outcomes, including Best Immunological Response Rate, anti-felzartamab antibody testing and titers, serum concentrations after multiple intravenous administrations, and adverse events during follow-up. When a study assesses multiple outcomes, the chance of at least one apparently notable result can increase if each is tested independently. General methods for addressing this include prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy or analyses for the outcomes.

The registry lists no analyses. It does not report a statistical analysis plan, a missing-data method, imputation procedures, or rules for handling participants with incomplete follow-up. The counts are accompanied by participants at risk within each cohort and period, but the record does not explain whether all participants completed each observation period or how missing observations were handled. The amount and pattern of missing data are not reported in the registry record.

The stated primary population is the Safety Analysis Set, consisting of participants who received at least one dose of study drug. This is a treatment-exposed safety population, not necessarily the same as every person enrolled. The registry record does not provide further analysis-population definitions or participant-level accounting for inclusion in each outcome. It is therefore not possible from the registry entry to assess how incomplete data, exclusions, or outcome-specific populations may have affected the reported counts.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: foot fracture (7.7%), neutropenia (7.7%), type i hypersensitivity (7.7%), gout (7.7%), infusion related reaction (5.6%).

Serious adverse-event counts are reported separately from counts of other adverse events. During Weeks 1-24, Cohort 1 had 2 participants with serious adverse events among 18 at risk, and Cohort 2 had 3 among 13 at risk. During Weeks 25-52, each cohort had 1 participant with a serious adverse event: Cohort 1 had 18 at risk and Cohort 2 had 13 at risk. The registry lists zero deaths in each cohort-period entry.

These figures describe the entries in the registry; they do not establish that MOR202 caused the events. The adverse-event definition explicitly includes events without regard to the possibility of a causal relationship. Seriousness is based on the registry’s criteria, which include outcomes such as life-threatening events and hospitalization, as well as specified medical events. It is not synonymous with severity or drug attribution.

The record also names serious adverse-event terms with percentages, including Foot fracture, Neutropenia, Type I hypersensitivity, Gout, Infusion related reaction, and Cerebrovascular accident. The denominator for these percentages is not reported in the registry record. These term-specific values therefore should not be treated as direct cohort comparisons. The record’s counts are descriptive, and it does not report a randomized control group or inferential safety analysis.

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

The registry record describes a completed open-label study of MOR202 in adults with anti-PLA2R antibody positive membranous nephropathy. Its posted adverse-event data show serious and other event counts among participants in the newly diagnosed or relapsed cohort and the refractory cohort, during treatment and follow-up. The record also lists serious-event terms and percentages, and zero deaths in each cohort-period entry. These observations are relevant to describing what was recorded in the study population.

The results do not establish that MOR202 caused or prevented any event. The adverse-event definition includes occurrences regardless of possible causal relationship, and the record does not give a causal analysis. Nor do the counts demonstrate that the treatment is effective or ineffective. The primary outcome concerns adverse events, while secondary outcomes address immunological response and other measures; the registry record does not list analyses for these outcomes.

The study also does not supply a randomized comparison with another treatment or a control group. Its cohorts differ by disease status and should not be interpreted as equivalent comparison groups. The observed counts cannot separate the influence of treatment from participant characteristics, other factors, or chance. With no inferential analyses or confidence intervals reported in the registry record, the precision of comparative effects cannot be assessed.

Accordingly, the appropriate interpretation is descriptive and limited to the participants and periods recorded. The results do not support a causal treatment claim, a comparison with standard care, or conclusions about people beyond the study population. The registry record does not report the missing-data approach, sample-size justification, or statistical analysis plan, which further limits assessment of how the results were analyzed.

14. Why This Trial Matters Statistically

This study is statistically informative in part because it illustrates the distinction between a safety description and a comparative treatment-effect analysis. The registry records participant counts for serious and other adverse events across treatment and follow-up periods. Those data can describe what was observed in the treated cohorts, but a count alone does not estimate the difference that would have occurred under a control treatment.

The design makes that distinction important. The trial was non-randomized, open-label, and single-group, with cohorts defined by whether participants were newly diagnosed or relapsed, or had refractory disease. Although both cohorts received MOR202, their different clinical descriptions make them unsuitable as direct control groups for each other. A numerical contrast between cohort counts would not isolate a treatment effect.

The endpoint definition also matters. It counts participants with adverse events without requiring a causal link to study drug. This broad safety definition captures untoward occurrences but cannot by itself identify drug-attributable harm. Separately reported serious events provide a clinically important classification, while still requiring caution about causality and denominators.

Finally, the registry record lists no analyses and does not report key statistical planning details such as the sample-size justification or missing-data method. These omissions restrict evaluation of precision and analytic choices. The case therefore highlights why design, outcome definition, analysis population, follow-up, and reporting of uncertainty all matter when interpreting clinical-trial results.

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 non-randomized, single-group design is a central limitation for causal interpretation. There was no randomized control group, and Cohort 1 and Cohort 2 were defined by different disease-status descriptions. Their event counts should not be treated as estimates from interchangeable groups or as a direct comparison of treatment strategies. The open-label design also means masking was absent; the registry record does not describe procedures intended to reduce any effect of awareness on event reporting or assessment.

The primary endpoint is described as the number of participants with adverse events from Week 1 to Week 24, but the reported event entries distinguish serious from other adverse events. A combined count for participants with any adverse event under the primary endpoint is not reported in the registry record. The record does not provide confidence intervals, inferential analyses, or an analysis of causal attribution. The denominator and further context for the listed serious-event percentages are also not reported.

Important details about the statistical plan are not reported in the registry record, including sample-size justification, missing-data handling, interim analyses, and multiplicity procedures. The record identifies the Safety Analysis Set as participants who received at least one dose, but does not provide further analysis-population details or a full account of incomplete follow-up. These limitations constrain assessment of precision, potential bias, and the completeness of the outcome data.

The cohort and period counts describe the participants recorded, but do not account for differences in exposure or observation time beyond the stated treatment and follow-up windows. The registry does not report enough information to determine how such differences might affect comparisons. The findings should therefore be read as descriptive registry results rather than as a comparative estimate of treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) — NCT04145440.
• Registry record last updated 2025-02-24; status last verified 2025-02.
• Results first posted 2024-12-24.
• 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

NCT04145440 is listed as a completed Phase Ib/IIa, open-label, multicenter study of MOR202 in adults with anti-PLA2R antibody positive membranous nephropathy. Enrollment was 31. The study began on 2019-10-15 and its primary completion date was 2022-01-19. It was non-randomized, unmasked, and single-group.

The study included newly diagnosed or relapsed participants in Cohort 1 and participants with refractory disease in Cohort 2. Both cohorts received MOR202 by intravenous infusion over 6 treatment cycles of 28-days each. The primary endpoint was the number of participants with adverse events from Week 1 to Week 24, in the Safety Analysis Set of participants who received at least one dose.

The registry reports serious and other adverse-event counts during treatment and follow-up, along with selected serious-event terms and percentages. It lists no analyses. The registry record does not report a randomized control comparison, the statistical analysis plan, sample-size justification, or methods for missing data.