This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Adrenocorticotropic Hormone in Membranous Nephropathy (NCT03025828), a na phase 4 study. The primary outcome is Change in Proteinuria.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03025828 |
| Phase | Phase 4 |
| Condition | Membranous Nephropathy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Icahn School of Medicine at Mount Sinai |
| Results posted | Yes |
2. Clinical Question
Population
Patients with membranous nephropathy were eligible for the study. The registry lists enrollment as 5. It does not provide further details about eligibility criteria or the characteristics of participants included in the primary outcome analysis.
Intervention
Participants received Acthar, also described as adrenocorticotropic hormone (ACTH). The registry describes subcutaneous administration at 80 units for the first week, followed by 80 units twice weekly.
Comparator
The study is listed as single-group, with allocation recorded as NA and masking as none. No concurrent control group or randomized comparison is described. The primary comparison is within the group, between baseline and 12 months.
Primary question
The primary outcome asks how proteinuria changed from baseline to 12 months of treatment, measured using the urine protein/creatinine ratio. The registry specifies the median and interquartile range as the summary measures, but does not report their values or a numerical change estimate.
This design addresses a before-and-after question: whether the recorded proteinuria measure differed at the specified follow-up from its baseline value among participants receiving Acthar. It does not directly estimate how outcomes would have differed under an alternative treatment or no treatment. Without a concurrent comparator, observed changes cannot by themselves separate a treatment-associated change from other explanations, including the course of the condition over time, changes in measurement, or other influences not described in the record.
3. Trial Design
The registry describes NCT03025828 as a completed Phase 4 study titled “Adrenocorticotropic Hormone in Membranous Nephropathy.” Its official title identifies changes in autoreactive memory B cells as a possible biomarker of response, while the brief summary describes evaluation of ACTH in relation to proteinuria and mechanisms of action. The listed condition is membranous nephropathy, and the sponsor is Icahn School of Medicine at Mount Sinai.
The design is recorded as single-group, with allocation listed as NA and masking listed as none. These entries mean the record does not describe random assignment to comparison groups or masking. The intervention is Acthar, administered subcutaneously at 80 units for the first week and then 80 units twice weekly. The record lists enrollment as 5. It does not provide a fuller account of participant flow, adherence, treatment interruptions, or the number contributing data to each outcome.
The study began on 2018-03-19, had primary completion on 2020-12-16, and is recorded as completed. These dates describe the registry timeline; they do not establish when each participant began or finished treatment. The primary outcome is change in proteinuria from baseline to 12 months, measured by urine protein/creatinine ratio and summarized with the median and interquartile range.
Secondary outcomes listed include remission status, serum albumin, estimated glomerular filtration rate, anti-PLA2R memory B cells, anti-PLA2R antibody levels, and a T-cell ratio. Their presence indicates a broader set of clinical and biomarker measurements, but the record does not describe the analysis plan for them. No randomized or like-for-like control comparison is reported, so the design supports descriptive within-group assessment rather than a controlled estimate of comparative treatment effect.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Acthar |
|---|---|
| STARTED | 5 |
| COMPLETED | 4 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Acthar |
|---|---|
| Lost to Follow-up | 1 |
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.
| Characteristic | Unit | Acthar |
|---|---|---|
| Participants analysed | 4 | |
| Age, Continuous | years | 53.75 (SD 8.098) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 4 |
| Race and Ethnicity Not Collected | Participants | — |
| Serum albumin | g/dL | 3 (SD 1.01) |
| Serum creatine | mg/dL | 0.965 (SD 0.118) |
| Negative for Anti-PLA2R Ab | Participants | 4 |
| Urine protein/creatinine ratio (P/C) | g/g | 6.173 (SD 3.545) |
| Number of Participants with previous treatment | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Proteinuria, measured over baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in proteinuria, assessed by urine protein/creatinine ratio at baseline and after 12 months of treatment. Proteinuria means protein loss in urine; the registry’s brief summary identifies this as the outcome of interest. The ratio relates urine protein to urine creatinine, a measurement commonly used in general clinical practice to help interpret urinary protein while accounting for variation in urine concentration. This general rationale does not establish how measurements were collected or handled in this study; those details are not reported in the registry record.
The registry specifies the median as the summary measure and the interquartile range as its dispersion measure. In general, the median describes the center of ordered observations and is less affected by extreme values than the mean. The interquartile range describes the spread of the middle half of the observations. These summaries can be useful when data are skewed or include unusually high or low values, but they do not show the full distribution or uncertainty around a treatment effect.
The record defines the measurement times as baseline and 12 months, but does not give the numerical median, interquartile range, participant-level changes, or a formal effect estimate. It also does not report a confidence interval or statistical test for this endpoint. Consequently, the endpoint definition clarifies what was intended to be measured, but the registry record does not allow the magnitude or precision of the observed change to be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record describes a primary outcome but does not report its numerical result. It identifies change in proteinuria, measured by urine protein/creatinine ratio between baseline and 12 months, and specifies median and interquartile range as the summary measures. Without those values, the direction and magnitude of any observed change cannot be determined from the record. No confidence interval, p-value, or other numerical analysis of the primary outcome is reported.
The single-group structure also constrains interpretation. A baseline-to-follow-up comparison can describe how measurements changed over time among participants in the group. It cannot, on its own, establish what would have happened over the same period without Acthar or under another treatment. General statistical reasoning is that an uncontrolled before-and-after change can reflect several influences, including the condition’s natural course, participant circumstances, measurement variability, or co-interventions. The registry record does not describe these influences or provide a design that separates them from treatment exposure.
Enrollment is listed as 5, while the safety figures separately list 4 at risk. These are different registry entries and should not be treated as interchangeable analysis counts. The record does not explain the difference, identify the number with primary outcome data, or describe participant flow. It is therefore not possible to determine from the record whether the primary outcome summaries, if calculated, would include all enrolled participants or a subset.
The registry lists 7 outcome measures and 0 analyses. The secondary outcomes include clinical measures and immune-cell or antibody measures, but no numerical outcome estimates or analysis results are presented in the record. Their listing does not establish that each measure was collected successfully, analyzed, or associated with a particular finding.
Any planning illustration associated with an observed effect should be understood as a hypothetical design calculation, not as an outcome of this trial or as observed power. The described assumptions are 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. These assumptions do not match the registry’s single-group design, and no numerical planning values are reported in the record. The sponsor’s own analysis would take precedence if a discrepancy were identified, but no sponsor analysis is reported.
9. Statistical Methods Explained
The registry identifies a median and interquartile range for the primary outcome. In general, these are descriptive statistics. The median is the central value after observations are ordered, while the interquartile range describes the spread of the middle half. Unlike the mean and standard deviation, these summaries are less directly influenced by very extreme observations. They can be informative for a measure whose distribution is not symmetric. However, the record does not provide the actual summaries, so their use cannot reveal the observed value or change in this study.
The endpoint is framed as change between baseline and 12 months, but the registry does not specify the exact calculation used to derive an individual participant’s change or the group-level summary. For example, it does not state whether the primary summary was based on participant-level differences or on a comparison of the distributions at the two time points. Those approaches answer related but not identical descriptive questions. The record also does not state whether values were transformed, whether repeated measurements were modeled, or how values outside expected ranges were handled.
In general, a confidence interval communicates the range of effect values reasonably compatible with the data and the assumptions of the analysis. Its width reflects statistical precision: a wider interval indicates less precision than a narrower interval. A p-value, when used, describes how unusual the observed data or more extreme data would be under a specified null hypothesis and model. Neither statistic establishes clinical importance by itself. The registry record does not report a confidence interval, p-value, or inferential model for the primary outcome, so statistical uncertainty and compatibility with a no-change hypothesis cannot be evaluated from the posted record.
The design is single-group rather than randomized. In a randomized comparison, treatment groups can provide a basis for estimating a contrast between assigned strategies, subject to the quality of conduct and analysis. Here, the primary outcome is a within-group baseline-to-follow-up assessment. In general, repeated measurement can identify temporal change, but a time contrast without a control group does not isolate the effect of treatment from other time-varying influences. This is a design limitation, not a question of choosing a more sophisticated statistical test.
Over-dispersion is a general issue when outcomes are more variable than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too small and inferential conclusions too confident. For count or event outcomes, models may need to account for variability beyond the simplest assumptions. The registry record does not identify a model for the listed outcomes, report dispersion diagnostics, or indicate whether over-dispersion was assessed. It would therefore be inappropriate to infer that a particular correction was or was not used.
The record lists 0 analyses. This means it does not present a registry-recorded analysis result for the outcomes in this entry; it does not establish that no analysis was performed outside the registry. The record also does not report an analysis population, a protocol-defined primary analysis set, or methods for handling missing observations. Those details are important because the interpretation of a follow-up summary depends on who contributed data and how absent measurements were treated.
Planning sample sizes and power calculations are distinct from observed trial results. In general, a planning calculation asks how much information a future design might need under stated assumptions. It does not describe the precision actually achieved in a completed study and should not be called observed power. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a fraction of the observed effect. These are illustrations for a two-arm planning scenario, not the design recorded for this single-group trial. No numerical planning estimates or effect size are reported in the registry record.
Multiplicity is the general issue of drawing inferences across multiple outcomes, time points, subgroups, or tests. Conducting many tests can increase the chance of at least one apparently notable result by chance if no adjustment or prespecified hierarchy is used. The registry names several secondary outcomes, but does not report a multiplicity procedure, a hierarchy of hypotheses, or which outcomes were confirmatory. It also does not give enough analysis detail to determine which tests, if any, were performed. Any interpretation of multiple outcome findings would therefore require information beyond this registry entry.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and several secondary outcomes, but does not report how multiplicity was addressed. In general, multiplicity arises when researchers assess more than one outcome or conduct multiple tests; without a prespecified strategy, interpreting isolated statistically notable results can be difficult. Possible strategies in general include selecting one primary hypothesis, defining an ordered testing hierarchy, or adjusting inference across a family of tests. The record does not state whether any such approach was planned or applied.
Missing-data methods are not reported in the registry record. It does not describe whether participants missed visits, whether endpoint measurements were unavailable, how incomplete records were handled, or whether any imputation or sensitivity analysis was used. These details matter because a follow-up summary can represent a selected subset if outcome data are absent. No analysis population or participant flow for the primary endpoint is reported, so the relationship between enrollment and outcome data cannot be assessed.
The record does not identify an intention-to-treat, per-protocol, or other analysis population. It does not state how treatment adherence, discontinuation, or deviations from the administration schedule were incorporated into analysis. Nor does it report a statistical analysis plan or a prespecified approach to the secondary outcomes. The completed status and the presence of outcome definitions do not supply these missing methods. Consequently, the registry entry does not support an assessment of whether analyses followed a prespecified plan or how robust findings might be to alternative choices.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Acthar | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Acthar | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Acthar | 0 of 4 |
The safety entry lists 4 participants at risk in the Acthar group. It records 0 serious adverse events, 0 other adverse events, and 0 deaths. No top serious-event terms are listed. These are the registry’s recorded counts; they describe what is entered for this safety record and do not provide information about event types beyond the categories shown.
These figures should be read with the size of the safety denominator and the limits of registry reporting in mind. A recorded count of zero does not prove that an event is impossible or establish that no event occurred outside the scope of the reported data. The registry does not describe the safety collection period, event definitions, completeness of reporting, or how the 4 participants at risk relate to the enrollment entry of 5. No explanation for that difference is reported.
Counts alone do not estimate comparative safety because no concurrent control group is described. They also do not provide a detailed account of severity, timing, relationship to treatment, or exposure duration. The record supports a narrow description of the events recorded in this entry, not a broader conclusion about the safety profile of Acthar.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed study was designed to examine ACTH in membranous nephropathy, with proteinuria measured by urine protein/creatinine ratio at baseline and 12 months as the primary outcome. It also lists immunologic and other clinical measures as secondary outcomes. These design details help identify the scientific question and the intended measurement, but they do not establish what the study found.
The primary outcome’s numerical results are not reported in the registry record. There is no reported median, interquartile range, effect estimate, confidence interval, or statistical test result for the stated baseline-to-12-month comparison. As a result, the record does not show the direction, size, or precision of any observed change. A missing numerical result should not be interpreted as evidence of no change, and it should not be treated as evidence of a particular benefit or harm.
Even if a within-group change were reported, this design would not by itself establish that Acthar caused the change. There is no randomized comparator in the registry description, and no masking is listed. General statistical interpretation distinguishes a temporal association in one group from a comparative treatment effect. The latter requires a suitable comparison and analysis, along with sufficient information about participants and outcome data.
The safety entry records zero serious adverse events, zero other adverse events, and zero deaths among 4 at risk. Those registry counts are descriptive and do not prove absence of risk. The limited safety information and lack of a comparator prevent broader comparative conclusions. Overall, the record is useful for understanding the study’s question, design, and outcome definitions, but its reported results are insufficient to assess the magnitude or precision of clinical or biomarker findings.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it separates the clarity of a research question from the strength of evidence available to answer it. The registry specifies a population, intervention, primary measure, and follow-up time. Those elements make the intended within-group question understandable. Yet the absence of numerical primary outcome results means that the magnitude and precision of any observed change cannot be evaluated from the registry record.
The single-group design highlights the distinction between observing change and estimating a treatment effect. Baseline and follow-up measurements can describe a trajectory in the treated group. Without a concurrent comparator, the analysis cannot show how that trajectory differs from what would have occurred under another strategy. This distinction is important whenever before-and-after data are discussed, particularly when a result might otherwise be interpreted causally.
The record also illustrates why reporting denominators and analysis populations matters. Enrollment is listed as 5, whereas the safety entry lists 4 at risk. The record does not explain the relationship between these entries or provide the number contributing primary outcome data. Without participant flow and missing-data information, a reader cannot judge how representative an outcome summary would be of everyone enrolled.
Finally, a list of outcomes is not the same as a report of findings or a statistical analysis plan. Multiplicity methods, missing-data methods, inferential results, and analysis populations are not reported. These omissions limit reproducibility and the ability to assess uncertainty. The statistical lesson is not that the study had no value, but that design details and outcome definitions cannot substitute for transparent numerical results and analysis reporting.
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.
Important limitations specific to this study are apparent from the registry record. It describes a single-group study with allocation recorded as NA and no masking. There is no concurrent control group, so a baseline-to-12-month change cannot provide a controlled estimate of comparative treatment effect. The record does not report randomization, and the design should not be interpreted as a randomized comparison.
The registry lists enrollment as 5, while the safety record lists 4 at risk. It does not explain this difference, report participant flow, or state how many participants contributed data to the primary outcome. Missing-data handling, adherence, discontinuation, and analysis populations are not reported. These omissions make it difficult to assess completeness and the population represented by any outcome summary.
The record defines the primary outcome and its descriptive summaries but gives no numerical results, confidence interval, or statistical test. It lists 7 outcome measures and 0 analyses, without a reported multiplicity strategy or a statistical analysis plan. The relationship between the study’s biomarker focus and any measured response is therefore not assessable from numerical findings in this record.
The safety entry reports counts but does not describe event definitions, timing, collection procedures, or treatment attribution. The registry timeline and completed status do not fill these gaps. These limitations concern what can be concluded from the registry entry; they do not establish that unreported procedures or analyses were absent outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Adrenocorticotropic Hormone in Membranous Nephropathy — NCT03025828.
- Registry record last updated 2022-08-15; status last verified 2022-07.
- Results first posted 2022-08-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT03025828 is a completed Phase 4, single-group study of Acthar in membranous nephropathy, sponsored by Icahn School of Medicine at Mount Sinai. The registry lists enrollment as 5, allocation as NA, and masking as none. Acthar was described as subcutaneous administration at 80 units for the first week, followed by 80 units twice weekly.
The primary outcome was change in proteinuria, measured by urine protein/creatinine ratio at baseline and 12 months, with median and interquartile range specified. Secondary outcomes include remission, kidney-function and albumin measures, and immune-cell and antibody measures. Numerical primary and secondary outcome results, analysis methods, missing-data procedures, and multiplicity methods are not reported in the registry record. The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths among 4 at risk.