Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease (NCT04009668), a na phase 2 study. The primary outcome is Change in Urine MCP1/Cr Levels.

2. Clinical Question

This is a biomarker-focused proof-of-concept question, rather than a randomized comparison of adalimumab against another treatment or no treatment. The registry describes the study as investigating whether adalimumab changed urine biomarker levels, including MCP1 and TIMP1. The designated primary measure is change in urine MCP1/Cr, expressed in ng/mg, with results intended to be described using a median and inter-quartile range.

The record lists an enrollment of 7 and describes the trial as phase 2. It also lists secondary outcomes involving adverse events, estimated glomerular filtration rate, urine protein creatinine ratio, and a combined urine protein response criterion. However, the registry record does not report the numerical primary or secondary outcome analyses. Thus, the stated research question can be identified, but the posted record does not establish the direction or size of any observed change.

3. Trial Design

This is a phase 2, single-group study sponsored by the University of Michigan. Its status is completed. The record gives a start date of 2019-10-02 and a primary completion date of 2023-09-05. Enrollment is listed as 7. These are trial-level registry entries; the record does not give further participant flow information or explain whether all enrolled participants contributed data to each outcome.

The intervention was adalimumab, described as a TNF-blocking treatment. The regimen was subcutaneous administration every other week at study weeks 0, 2, 4, 6, and 8. Masking is listed as none. Allocation is listed as not applicable, consistent with the single-group model. No randomized control group or like-for-like comparator is reported, so changes over time cannot be separated from other influences using a concurrent control contrast.

The primary endpoint is change in urine MCP1/Cr at 10 weeks. The record specifies a median and inter-quartile range as the statistical summary and gives the unit as ng/mg. Secondary outcomes listed are incidence of adverse events, change in eGFR, change in UPCR, and the proportion meeting both a nadir UPCR below 1.5 g/g and at least a 40% reduction from baseline. The registry lists 6 outcome measures, but the posted record lists 0 analyses. Numerical outcome results and the analysis methods actually applied are not reported in the registry record.

The title identifies FSGS and treatment-resistant MCD as the clinical focus, while the condition list includes FSGS and MCD. Eligibility criteria, the numbers with each condition, baseline disease features, and details of concomitant care are not reported in the registry record. The design therefore supports a description of how the study was structured, but not a controlled estimate of a 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.

Before assignment: Following consent, participants provided a urine sample to measure urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tissue inhibitor of metalloprotease-1 (uTIMP-1), two indicators of intra-renal tumor necrosis factor (TNF) pathway activation. Participants with present TNF activation were advanced to screening. Upon confirmation of eligibility, participants proceeded to the treatment phase.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Urine MCP1/Cr Levels, measured over 10 Weeks.

The primary endpoint is change in urine MCP1/Cr levels at 10 weeks, measured in ng/mg. MCP1 is described in the registry as an established marker of intra-renal TNF pathway activation. The biomarker values were measured by enzyme-linked immunosorbent assay (ELISA) and standardized over serum creatinine. The registry states that a reduction in MCP1 reflects a reduction in TNF pathway activation in the kidney.

Using a urine biomarker gives the study a measurable biological outcome related to its TNF-focused rationale. Standardizing the measurement over serum creatinine is part of the stated measurement approach. The record specifies that the endpoint is summarized by a median and inter-quartile range, rather than a mean and standard deviation. In general, the median describes the middle of an ordered set of measurements, while the inter-quartile range describes the spread of the middle half. This can be useful when measurements are skewed or when a small study makes the influence of extreme observations important.

The endpoint is a biomarker outcome, not by itself a direct measure of how participants feel, function, or experience a clinical event. A change in the marker may be relevant to the proposed pathway, but it does not alone establish a corresponding change in kidney function or urine protein. Those clinical measures appear among the listed secondary outcomes. The actual baseline and follow-up MCP1/Cr values, the median change, and its inter-quartile range are not reported in the registry record, so the observed biomarker pattern and its precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry labels the study as a single-group model, with allocation not applicable and no masking. In general, a single-group study follows people receiving an intervention without a concurrent control arm. If measurements before and after treatment are available, their change can be described, but a before-and-after contrast is not equivalent to a randomized treatment comparison. Time trends, measurement variation, or other influences may contribute to observed change. The registry does not report a statistical analysis plan explaining how these issues were addressed.

Why report a median and inter-quartile range?

The primary endpoint is described using a median and inter-quartile range. In general, the median is the center of ordered observations: half of the values lie at or below it and half at or above it, subject to ties and the way the median is defined for a given dataset. The inter-quartile range spans the middle half of observations. These summaries are often useful when data are asymmetric or include unusually high or low values, because the median is less sensitive to extremes than the arithmetic mean. They do not, by themselves, show how precisely an estimated treatment effect is known. The registry does not give the observed median, inter-quartile range, or a confidence interval for this endpoint.

What does MCP1/Cr represent?

The record describes MCP1 as a marker of intra-renal TNF pathway activation, measured by ELISA and standardized over serum creatinine. Its interpretation is therefore linked to a biological pathway. As a general statistical distinction, a biomarker is an intermediate measurement, not automatically a validated substitute for a clinical outcome. A change in a biomarker can be consistent with a change in the pathway it represents, but cannot alone establish changes in kidney function, proteinuria, or other patient outcomes. Those measures are listed separately as secondary outcomes. Their numerical analyses are not reported in the registry record.

What can a single-group change estimate establish?

In general, a within-group change describes how measurements differ across the observation period for the people measured. It does not provide the counterfactual outcome—what would have happened to the same people over that period without the intervention. A control group can help estimate that contrast when design and analysis are appropriate. No such group is reported for this study. The record also does not report whether the primary analysis used paired observations, how missing measurements were handled, or which participants were included in each analysis.

The enrollment is listed as 7, but that figure does not establish the number contributing to every endpoint. In general, attrition or missing measurements can make an endpoint’s analysis population smaller than enrollment, and the consequences depend on why observations are missing and how the analysis handles them. Participant flow, endpoint-specific denominators, and missing-data methods are not reported in the registry record.

How should planning calculations be read?

Any sample-size figures associated with planning for a fraction of an observed effect are illustrations, not observed evidence and not the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations depend on the assumed effect and the model. They do not describe the power achieved by this completed single-group study. The planning assumptions do not match the study’s listed single-group design, so the figures should not be interpreted as a prospective sample-size rationale for this trial. The registry does not report a sample-size justification or its own statistical plan.

Why do uncertainty and model assumptions matter?

In general, an estimate is more informative when accompanied by an uncertainty interval. A confidence interval gives a range of values compatible with the data and the interval’s assumptions; it is not a guarantee that the true value lies within that particular interval. In small studies, intervals can be wide, and conclusions may be sensitive to individual observations. The registry record does not report an interval for the primary endpoint.

The primary endpoint is summarized with a median and inter-quartile range, but no inferential test or model is listed. It would be inappropriate to infer a particular test from the summary format. The analysis population, handling of repeated measurements, adjustment for baseline values, covariate selection, and treatment of multiple endpoints are not reported in the registry record. General methods choices should be judged against the design and data structure, rather than assumed from the endpoint label alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures, including the primary urine MCP1/Cr endpoint and secondary safety and clinical outcomes. It lists 0 analyses. The numerical outcome findings, the number of outcomes tested, and any distinction between confirmatory and exploratory analyses are not reported in the registry record.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. Testing many hypotheses can increase the chance that at least one result appears notable by chance. Common approaches include designating a primary outcome in advance, adjusting inference across a defined family of tests, or clearly treating additional analyses as exploratory. The registry identifies a primary endpoint, but it does not report whether or how multiplicity was addressed for the listed outcomes or any additional analyses.

Missing-data handling and analysis populations are also not reported. The enrollment is listed as 7, but the record does not state how many participants contributed to each endpoint, whether any measurements were unavailable, how missing observations were handled, or whether analyses used all enrolled participants or a subset. These details matter because estimates can depend on which observations are included and why others are absent.

Interim analyses, stopping rules, and the prespecified statistical analysis plan are not reported in the registry record. No assumptions about these procedures can be made from the completed status or the listed endpoints. Without outcome-level results and analysis details, multiplicity, missingness, and analysis-population choices cannot be evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: influenza (14.3%), edema (14.3%), anasarca and aki (14.3%).

The registry’s adverse-event entry lists 7 at risk for serious adverse events and 1 affected. It lists 7 at risk for other adverse events and 5 affected. Deaths are listed as 0. The registry also identifies Influenza, Edema, and Anasarca and AKI among the top serious terms, with 14.3% beside each term.

These figures describe what is recorded, not whether an event was caused by adalimumab. An adverse event occurring during a study is not automatically an adverse reaction attributable to the intervention. The posted record does not give the event-level timing, duration, severity details beyond the serious-event category, or attribution assessment. It also does not make clear from these summary figures whether people could contribute to more than one listed term. The terms should not be added together to infer a count of affected participants.

The serious-event and other-event summaries should be read as separate registry entries. The percentages attached to the serious terms do not establish comparative risk because there is no control group reported. The record’s adverse-event figures are limited summaries and do not provide a complete comparative safety analysis.

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

The registry record establishes that this completed phase 2 study investigated adalimumab in FSGS and treatment-resistant MCD, with urine MCP1/Cr change at 10 weeks designated as the primary endpoint. It also specifies the biomarker measurement approach and lists clinical and safety outcomes. These details clarify the intended scientific question and what the study was structured to monitor.

What the posted record does not establish is the observed result. It contains no numerical primary endpoint analysis, so it cannot show whether MCP1/Cr changed, how large any change was, or how variable the measurements were. The numerical analyses for eGFR, UPCR, the combined proteinuria response, and adverse events are likewise not reported beyond the listed safety summary. The record therefore does not support a conclusion about the magnitude or precision of a biomarker or clinical outcome change.

Even with results, the single-group design would limit causal interpretation. In general, a change among treated participants cannot by itself distinguish an intervention effect from other changes over time. The absence of a reported comparator also means the study cannot provide a randomized estimate of how outcomes differ between adalimumab and an alternative. This is a design limitation, not evidence that the treatment did or did not affect outcomes.

The biomarker’s relationship to TNF pathway activation gives it a mechanistic role, but biomarker movement is not equivalent to a demonstrated clinical benefit. Interpretation would require the actual results, their uncertainty, the analysis population, missing-data information, and clinically relevant outcome findings. Those details are not reported in the registry record. Accordingly, the record supports a description of the study’s aim and design, but not a claim that adalimumab did or did not improve kidney outcomes.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it connects a mechanistic hypothesis to a measurable urine biomarker. The stated rationale links MCP1 with intra-renal TNF pathway activation, and the primary endpoint uses MCP1/Cr at 10 weeks to assess whether the marker changed during adalimumab treatment. That makes the study a proof-of-concept investigation of biological response, rather than a comparative efficacy trial.

The single-group structure also makes clear why design determines what an estimate can mean. A within-group pattern could be useful for generating a hypothesis, but it would not isolate a treatment effect in the way a valid concurrent comparison can. This distinction is essential when considering small early-phase studies, where the aim may be exploratory and uncertainty may be substantial. The registry lists enrollment as 7, but does not report the endpoint results needed to assess the biomarker pattern or its precision.

Statistically, the case also illustrates the importance of transparent outcome reporting. The record identifies 6 outcome measures and 0 analyses. Without numerical results, participant counts for each endpoint, uncertainty estimates, and methods for missing data or multiple outcomes, readers cannot judge the strength or robustness of the evidence. The study’s biological rationale and planned measures can inform future research questions, but they cannot substitute for posted outcome analyses.

The trial therefore matters as an example of the boundary between a research question and an answer supported by results. A defined biomarker, a stated timeframe, and a completed study status do not reveal the outcome in the absence of the analysis itself. Clear reporting of estimates and their uncertainty would be necessary for readers to assess what signal, if any, the study observed.

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 trial-specific limitation is the absence of numerical outcome analyses in the registry record. Although the primary endpoint and several secondary outcomes are defined, their observed results are not reported. This prevents assessment of the direction, magnitude, and precision of changes in MCP1/Cr, eGFR, or UPCR, and prevents evaluation of the combined UPCR response outcome.

The study is listed as single-group, with no masking and no like-for-like control comparison. Any change over time would therefore be difficult to attribute uniquely to the intervention. The record does not report a protocol or statistical analysis plan, a sample-size justification, or details of interim analyses. These omissions leave key design and analysis decisions unclear.

Enrollment is listed as 7, but endpoint-specific analysis counts, participant flow, and missing-data handling are not reported. The record also does not report baseline participant characteristics, the distribution of FSGS and MCD among enrolled participants, or whether results differed by condition. Such information would be important for understanding who contributed to the findings and how broadly they might apply.

The primary outcome is a biomarker rather than a direct clinical endpoint. Although the registry links MCP1 to TNF pathway activation, the record does not establish how a change in this marker relates to clinical outcomes in this study. Finally, safety summaries lack the event-level details needed to assess timing, attribution, and possible overlap among terms. These limitations concern what can be learned from the registry record; they should not be interpreted as evidence for or against a treatment effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease — NCT04009668.
• Registry record last updated 2024-10-30; status last verified 2024-10.
• Results first posted 2024-10-30.
• 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

NCT04009668 is a completed phase 2, single-group study sponsored by the University of Michigan. It lists an enrollment of 7, no masking, and no randomized comparator. Adalimumab was administered subcutaneously every other week at study weeks 0, 2, 4, 6, and 8.

The primary endpoint was change in urine MCP1/Cr at 10 weeks, reported in ng/mg and intended to be summarized using a median and inter-quartile range. Listed secondary outcomes include adverse events, eGFR change, UPCR change, and a combined UPCR response criterion. The registry lists 6 outcome measures and 0 analyses. Numerical outcome results and the statistical analysis plan are not reported in the registry record.