A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS) (NCT02000440), a na phase 2 study. The primary outcome is Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points.

2. Clinical Question

This is a proof-of-mechanism question rather than a comparative-effectiveness question. The endpoint asks whether participants met a prespecified combination of proteinuria reduction and renal-function criteria at specified treatment visits. Because there is no control group, any observed change would describe the study participants over time; it would not by itself establish how much of that change was caused by losmapimod rather than by other influences. The registry record states that the study also assessed safety, tolerability, and pharmacokinetics, but detailed results for those domains are not reported in the registry record beyond the adverse-event counts discussed separately.

3. Trial Design

This was a Phase II, repeat-dose, proof-of-mechanism study of losmapimod for proteinuria in focal segmental glomerulosclerosis. The design is described as single-group, multicenter, and open-label. Enrollment was 17. The brief description says the study anticipated approximately 21 subjects, while the recorded enrollment is 17; reasons for the difference are not reported in the registry record.

All participants were assigned to the losmapimod group. The study did not use random allocation and had no concurrent comparison arm. Masking was none, meaning the study is listed as open-label. These features matter when interpreting changes from baseline: without a control group, the record cannot separate a treatment-associated change from natural fluctuation, measurement variability, changes in care, or other influences. Open-label conduct can also affect participant behavior and outcome assessment, although the registry description does not report whether any particular assessment was blinded.

The planned treatment phase was 24 weeks, with a 12-week follow-up for safety and relapse assessments. The primary endpoint was assessed at Week 2, Week 4, Week 8, Week 16, and Week 24. The population description calls the completed-treatment population participants who completed >=16 weeks of treatment or withdrew; participants who withdrew before Week 16 were considered nonresponders. The endpoint description also says that only participants available at the specified time points were analyzed. Further details about how these rules were applied in each analysis are not reported in the registry record.

The record lists 17 outcome measures and no analysis entries. It does not report a protocol-level statistical plan, a sample-size justification, interim analyses, or details of any model used to analyze outcomes. These absences limit assessment of how the study was planned and how the endpoint was handled beyond the definitions recorded for the outcome.

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 29 participants were screened and entered into the run-in phase, of which 17 participants received at least one dose of losmapimod.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Completed Treatment Population: comprised of participants who had completed \>=16 weeks of losmapimod treatment or who withdrew from the treatment. Participants who withdrew prior to Week 16 were considered as non-responders.

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: Losmapimod 7.5 mg BID / 15 mg BID

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points, measured over Week 2, Week 4, Week 8, Week 16 and Week 24.

The primary endpoint is a count of participants who met the registry’s definition of response at each specified visit. Response required both a >=50 percent reduction from baseline in 24-hour total protein and renal function at >=70 percent of baseline estimated glomerular filtration rate at the end of treatment, defined as >=16 weeks. It is therefore a composite responder definition: improvement in proteinuria alone does not satisfy the full definition unless the renal-function criterion is also met.

Proteinuria is described in the record as excess serum proteins in urine. Measuring change in urinary protein is relevant to the study’s stated aim of assessing reduction in proteinuria. Requiring a renal-function condition alongside the proteinuria threshold makes the responder definition more restrictive than a proteinuria-only measure. It attempts to describe participants who meet the proteinuria target while also meeting a specified renal-function condition.

A binary endpoint converts each participant’s status at a given assessment into whether the responder definition was met or not met. The count can be easy to interpret, but it does not show how far each participant’s proteinuria changed, how close nonresponders came to the threshold, or the pattern of change over time. The registry lists percent change in urinary protein/creatinine ratio and complete proteinuria remission among secondary outcomes, but their results are not reported in the registry record.

The number of responders at the listed visits is not reported in the registry record. Without those counts, the primary endpoint cannot be characterized in terms of the observed response frequency or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how observations are converted into estimates and how much uncertainty surrounds those estimates. In this record, the endpoint is a participant count based on a binary definition: each participant either satisfies the responder criteria at a specified assessment or does not. Counts are often presented alongside the number assessed, because a count without its denominator does not show the frequency within the group. The record’s endpoint description notes that the analyzed number could vary by visit, but the actual responder counts and visit-specific denominators are not reported in the registry record.

What does the responder definition capture?

The endpoint combines two conditions. The first is a reduction of >=50 percent in 24-hour total protein from baseline. The second is renal function at >=70 percent of baseline estimated glomerular filtration rate at the end of treatment, defined as >=16 weeks. A participant must satisfy both parts to count as a responder. This construction can be useful when an outcome is intended to capture improvement on one measure subject to a condition on another. It also means that a participant who meets the proteinuria criterion but not the renal-function criterion is not counted as a responder under this definition.

Binary classification simplifies interpretation but discards detail. Participants just below a threshold and participants far below it are both classified as nonresponders, even though their measured values may differ. Similarly, a participant meeting the threshold is counted as a responder without the count conveying the size of the change beyond that threshold. Continuous outcomes, such as change in urinary protein/creatinine ratio, can retain more information about magnitude, although they require their own choices about summaries and models. The record lists such measures among secondary outcomes, but results and analytic details are not reported in the registry record.

Why does the single-group design matter?

A single-group study can describe measured outcomes among people who received the intervention. It cannot directly estimate a contrast with a concurrent control group because no such group is included. In a randomized comparison, the treatment groups can provide a basis for estimating a between-group difference under the assumptions of the design and analysis. Here, any before-and-after pattern would remain vulnerable to influences that change over time, including natural variation and measurement variability. That is a general limitation of uncontrolled longitudinal comparisons, not a finding about what happened to participants in this study.

The study is open-label and has no masking. In general, knowledge of treatment assignment can influence behavior, reporting, or decisions about assessment. The registry record does not report whether particular measurements were independently assessed or whether procedures were used to limit such influences. The absence of masking should therefore be considered when evaluating subjective outcomes, while the record does not establish that bias occurred.

How should uncertainty be assessed?

A confidence interval is a range calculated from data and a statistical method to express uncertainty around an estimate. For a binary endpoint, an interval around a response proportion can communicate how imprecisely the observed group frequency is estimated. A point estimate alone does not show that uncertainty. The registry record does not report a primary endpoint estimate, confidence interval, or p-value, so there is no primary-outcome precision estimate to interpret. General concepts about confidence intervals cannot substitute for the missing study results.

For a count endpoint, the denominator is essential context. The population rules indicate that the number available for analysis could differ by visit. If the denominator changes, counts at different visits may not be directly comparable as though they came from an unchanged set of participants. The registry record does not give visit-specific denominators or a detailed account of the analysis population at each visit.

What do the listed planning assumptions mean?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says that the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm. These assumptions describe a planning calculation, not the actual single-group design of this trial. They do not make the study randomized or create a control arm. The number of participants required by any illustration is not an observed result, and sample-size planning is not observed power. Numerical planning values are not reported in the registry record.

The registry record lists no analysis entries. It does not report whether a specific regression model, adjustment method, or inferential procedure was used for the primary outcome. It also does not report a statistical analysis plan or a sample-size justification for the actual study. Those methods should not be inferred from the endpoint type or from general statistical practice.

Why can event rates vary more than a simple model expects?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It matters when a model assumes a particular level of variation, because underestimated variability can make uncertainty appear smaller than it is. This trial’s primary endpoint is a binary responder count, and the registry record does not report an analysis model or evidence that over-dispersion was assessed. Thus, over-dispersion is a general statistical concept rather than a reported feature of this analysis.

Interpretation of the endpoint would require the observed counts, denominators, and uncertainty estimates, together with transparent handling of missing visits. Because those details are not reported in the registry record, the methods explanation can clarify what the endpoint and design imply, but cannot reconstruct an analysis or quantify its precision.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is assessed at Week 2, Week 4, Week 8, Week 16, and Week 24. The record also lists 17 outcome measures, including responder status, urinary protein/creatinine change, complete remission, adverse events, withdrawals due to toxicities, blood pressure, heart rate, and liver-function parameters. Examining multiple outcomes and time points creates a multiplicity issue: when many statistical questions are considered, the chance of at least one apparently unusual result can increase. In general, a prespecified strategy can define which outcome or time point is primary and whether adjustment is needed for other comparisons. A multiplicity strategy is not reported in the registry record.

The primary endpoint description says that only participants available at the specified time points were analyzed. The completed-treatment population is described as including participants who completed >=16 weeks of treatment or withdrew, with participants withdrawing before Week 16 considered nonresponders. These statements describe aspects of the analysis population and early withdrawal handling, but visit-specific participant counts and details of implementation are not reported in the registry record.

Missing observations can affect estimates when participants with unavailable measurements differ from those with measurements. In general, complete-case analysis uses observations that are available, while imputation uses a stated method to fill in missing values for analysis. Neither the missing-data pattern nor an imputation method is reported in the registry record. The nonresponder rule for withdrawal before Week 16 is a stated endpoint-population rule; it does not establish how every other missing value or missed visit was treated.

A protocol-level statistical analysis plan, details of interim analyses, and a sample-size justification are not reported in the registry record. Without those details and without outcome estimates, it is not possible to assess whether all planned analyses are represented or how multiplicity and missing observations affected the reported findings.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 17 participants at risk for serious adverse events and 0 participants affected. It lists 17 participants at risk for other adverse events and 16 participants affected. These are counts within the losmapimod group. The record does not provide a concurrent control group, so the counts cannot be used to estimate a comparative difference in event frequency.

A participant count does not describe the total number of event episodes, their timing, duration, severity, or clinical course. The registry record lists no serious adverse-event terms. It also does not report deaths. The categories should be read as the registry’s affected-participant counts, rather than as a complete account of every clinical detail for each event.

In general, an adverse event occurring during a study is not automatically established as caused by the treatment. Causal attribution requires clinical assessment and an appropriate design and analysis; the counts alone do not determine causality. The record also does not provide the detailed event descriptions needed to evaluate patterns or compare risks across treatment groups. The reported counts describe what was recorded in the treated group and should not be interpreted as proof of either safety or harm.

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

The registry record establishes that this was a single-group, open-label Phase II study of losmapimod in participants with idiopathic focal segmental glomerulosclerosis and substantive proteinuria. Its primary outcome was a count of participants meeting a combined proteinuria and renal-function definition at specified visits. That endpoint definition clarifies what the study intended to count, but the count itself is not reported in the registry record.

Without the primary outcome results, the record does not show how many participants met the responder definition, how often it was met at different visits, or how precisely any response frequency was estimated. The listed secondary outcomes also do not include numerical results in the available record. The safety counts that are reported are descriptive: 0 of 17 participants had a recorded serious adverse event, and 16 of 17 had a recorded other adverse event. These figures do not establish cause and do not support a comparison with another treatment.

The single-group design is important to what the study can establish. A change from baseline, if reported, would describe change during follow-up among participants receiving losmapimod. In the absence of a control group, it would not distinguish treatment effects from time trends, natural variability, measurement variability, or other influences. Open-label conduct also means treatment assignment was not masked, although the record does not establish that this affected any outcome.

The record’s proof-of-mechanism framing and endpoint definitions describe the questions the study set out to examine. They do not replace observed results. The registry record does not report the primary endpoint counts, confidence intervals, p-values, or a detailed statistical analysis plan. Consequently, it is not possible to quantify the size or precision of a proteinuria response, determine whether the response definition was met at particular visits, or draw a controlled causal conclusion from the record.

In general, clinical interpretation of an intervention depends on observed outcomes, uncertainty, safety information, and the design’s capacity to distinguish treatment effects from other explanations. Here, the design and available reporting support a description of study conduct and the stated endpoint criteria, with limited descriptive safety counts. They do not support a complete quantitative assessment of efficacy or comparative safety.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a specific responder definition with repeated assessments in a single-group study. The endpoint requires both a substantial reduction in 24-hour total protein and a renal-function condition. That joint definition illustrates how clinical outcomes can use more than one criterion to classify response. It also emphasizes why the exact endpoint matters: counts refer to participants satisfying the full definition, not simply participants whose proteinuria changed.

Assessment at Week 2, Week 4, Week 8, Week 16, and Week 24 could describe whether the endpoint was met at different stages of treatment. Repeated measurement can offer information about timing, but it also raises questions about changing denominators, missing visits, and multiplicity. The record gives some population rules, including treatment of withdrawals before Week 16, but does not report visit-specific counts, an explicit missing-data method, or a multiplicity strategy.

The design also demonstrates a central distinction between observing change and estimating a comparative treatment effect. A single-group study can document outcomes among treated participants, but without a concurrent control group it cannot provide a controlled contrast. That distinction remains important even when an endpoint has a clear threshold or assessments occur at several visits.

Finally, the registry record illustrates the difference between an endpoint being specified and its results being reported. The responder criteria and assessment times are described, but the primary outcome counts and uncertainty estimates are not reported in the registry record. The available safety counts are also descriptive rather than comparative. Interpreting a trial statistically therefore requires attention not only to the design and definitions, but also to whether the observed estimates and their precision are available.

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 for interpreting this trial is that the primary endpoint results are not reported in the registry record. The responder counts at the listed visits, visit-specific denominators, and estimates of uncertainty are unavailable. As a result, the record does not support a quantitative description of the primary outcome.

The study had one open-label treatment group and no concurrent control. This limits causal interpretation of any change from baseline and prevents a direct comparison with another treatment. The record does not describe blinded assessment procedures. It also does not report whether participants received other relevant care during the study, so no such details should be assumed.

The endpoint rules include a completed-treatment population and classify participants withdrawing before Week 16 as nonresponders. The endpoint description also states that only participants available at a specified time point were analyzed. The record does not provide enough detail to determine how these rules interacted at each visit, how missed assessments were handled, or whether any other missing-data method was applied.

The record lists multiple outcomes and primary assessment times, but a multiplicity approach is not reported. A statistical analysis plan, sample-size justification, interim analysis details, and methods used to estimate effects are also not reported in the registry record. The enrollment was 17, while the study description anticipated approximately 21 subjects; the reason for the difference is not reported.

Safety reporting is limited to affected-participant counts. Serious adverse-event terms and death counts are not reported in the registry record, and there is no control group for comparative safety interpretation. These limitations do not establish that an unreported event occurred or that a specific bias affected results; they define what can and cannot be concluded from the available record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS) — NCT02000440.
• Registry record last updated 2017-06-12; status last verified 2017-03.
• Results first posted 2017-06-12.
• 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

NCT02000440 is a completed Phase II, single-group, multicenter, open-label study of losmapimod in idiopathic focal segmental glomerulosclerosis. The registry records enrollment of 17 participants. The planned treatment phase was 24 weeks, followed by a 12-week follow-up for safety and relapse assessments.

The primary endpoint counted participants meeting both a >=50 percent reduction in 24-hour total protein from baseline and renal function at >=70 percent of baseline estimated glomerular filtration rate at the end of treatment, defined as >=16 weeks. Assessments were listed for Week 2, Week 4, Week 8, Week 16, and Week 24. Primary endpoint results are not reported in the registry record.

The adverse-event record reports 0 serious adverse events among 17 participants at risk and other adverse events in 16 of 17 participants at risk. There was no control group. Statistical analysis details, primary outcome estimates, and uncertainty measures are not reported in the registry record.