A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (NCT03448692), a non-randomized phase 2 study. The primary outcome is Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13.

2. Clinical Question

3. Trial Design

This was a Phase 2 study of PF-06730512 in adults with FSGS. Its official title describes a 24-week, adaptive, open-label, sequential-cohort trial; the registry lists the allocation as non-randomized and the model as sequential. The record identifies 47 enrolled participants and lists the study status as terminated. The reason for termination is not reported in the registry record.

The intervention was given as multiple intravenous infusions. The registry describes three sequential cohorts, with the third marked optional. It does not specify in those cohort descriptions which dose corresponds to each cohort. Separate serious adverse-event information lists PF-06730512 1000 mg IV and PF-06730512 300 mg IV groups. Because allocation was non-randomized, comparisons between those groups should not be interpreted as though participants had been randomly assigned to otherwise equivalent arms.

There is an unresolved design-description inconsistency: the official title calls the study open label, while the registry’s masking entry says triple. The record does not explain how these descriptions fit together. It also does not report the protocol details needed to clarify masking by role or phase.

The recorded start date is 2018-10-15, and the primary completion date is 2023-02-14. The primary endpoint concerns percentage change from baseline in UPCR at Week 13, measured with 24-hour urine collection. Other listed outcomes include adverse events, laboratory and electrocardiogram abnormalities, vital signs, body weight, and UPCR at other time points. The registry identifies Pfizer as the sponsor.

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 47 participants were enrolled into the study. All participants received treatment.

Disposition Phase:Screening:up to 43Days

Lead in Period:8 Weeks (W)

Investigational Treatment Period:Upto24W

Reasons for not completing this period:

Follow up Period:9 Weeks

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) was defined as all enrolled participants who had received at least one dose of study treatment and had at least one post-baseline measurement of UPCR based on 24-hour urine collection. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

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: Safety Analysis Set (SAS) was defined as all enrolled participants who had received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13, measured over Baseline, Week 13.

The primary endpoint is percentage change from baseline in urinary protein to creatinine ratio (UPCR), based on a 24-hour urine collection at Week 13. UPCR compares the amount of protein in urine with the amount of creatinine and is expressed in mg/mmol. The endpoint description notes that a decrease in UPCR may be associated with improved renal and cardiovascular function; that association is the stated rationale for measuring the endpoint, not a result of this trial.

Using a ratio relates urinary protein to creatinine in the same collection. The specified 24-hour collection defines how the measurements for this endpoint were obtained. Percentage change expresses a follow-up measurement in relation to baseline, so interpretation depends on both the baseline and Week 13 values and on the analysis used to summarize them.

The registry identifies the endpoint statistic as a least-squares mean and its uncertainty measure as a 90% confidence interval. The estimate and interval are not reported in the registry record. Consequently, the size, direction, and precision of the primary endpoint result cannot be described from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint summary as a least-squares mean with a 90% confidence interval. The model and the exact calculation used for this endpoint are not reported in the registry record. The statistical ideas below are general explanations and should not be mistaken for a description of an unreported analysis plan.

What does a least-squares mean represent?

In general, a least-squares mean is a model-based average. It can estimate an average outcome while accounting for terms included in a statistical model, such as baseline values or other specified factors. Which terms are included matters because the resulting estimate is conditional on the model. Here, the registry names the statistic but does not report the model formula, covariates, transformation, or estimation details. It is therefore not possible to say what adjustments, if any, were used or to reproduce the estimate from the record.

The endpoint is percentage change in UPCR from baseline to Week 13. In general, a percentage-change outcome describes change relative to a starting value, but its interpretation can be affected by the distribution of baseline measurements and by how missing follow-up values are treated. The registry does not report the observed endpoint values, the model diagnostics, or a sensitivity analysis for this outcome.

How should a confidence interval be read?

In general, a confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval’s location conveys the range of values compatible with the analysis. A 90% confidence interval is the uncertainty measure named for this endpoint. Its endpoints are not reported in the registry record, so neither its width nor which values it includes can be assessed.

A confidence interval does not by itself establish clinical importance or prove that a treatment caused an outcome. Interpretation also depends on study design, the analysis population, measurement quality, missing-data handling, and the comparison being made. Those details are particularly important in a non-randomized sequential study, where changes over time or differences in participant characteristics may be entangled with cohort or dose.

What does non-randomized, sequential allocation imply?

In general, random allocation helps balance measured and unmeasured participant characteristics across comparison groups. Non-randomized allocation does not provide that protection by design. Sequential cohorts can also differ because they enter at different stages of a study. These features do not make descriptive results unusable, but they limit how confidently an observed difference can be attributed to treatment or dose. The registry explicitly says the listed arms are not a like-for-like control comparison.

The record describes a 24-week adaptive, sequential-cohort trial, but it does not report the adaptation rules, decision criteria, or dose-selection process. These details cannot be inferred from the study title. Nor is an interim-analysis plan reported in the registry record.

What can the planning illustrations tell readers?

Planning illustrations are not observed trial outcomes and are not a measure of the trial’s observed power. The stated illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. The record says that time-to-event illustrations use total events, while other illustrations use participants per arm. These are planning assumptions, not a description of the trial’s actual allocation or an independent sample-size justification.

The observed effect required to anchor those illustrations is not reported in the registry record. The record also does not report the original sample-size justification. Thus, the illustrations should not be read as evidence that the study was designed to detect a particular clinically meaningful effect, or that it had a particular probability of detecting an effect.

Why does multiplicity matter?

In general, evaluating several outcomes or time points creates multiple opportunities to observe an apparently notable result by chance. Statistical plans may address this through a prespecified hierarchy, adjustment, or other strategy. The registry lists multiple outcome measures, including UPCR at several weeks, but it does not report a multiplicity strategy. With no posted endpoint analyses, it is not possible to assess how multiplicity was handled in practice or how it should affect interpretation of any result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary Week 13 UPCR endpoint and secondary measures covering adverse events, laboratory findings, body weight, blood pressure, pulse rate, body temperature, electrocardiogram findings, and UPCR at other specified weeks. Considering multiple outcomes and time points can raise multiplicity concerns. In general, a prespecified statistical strategy can control how multiple tests are interpreted, but that strategy is not reported in the registry record.

The registry reports zero analyses. The primary endpoint estimate and 90% confidence interval are not posted, and the record does not provide p-values or an outcome-level analysis for the listed measures. A hierarchy of endpoints, any adjustment for multiple comparisons, or the handling of any adaptive decisions is not reported in the registry record. It is not possible to determine whether such methods were absent from the study protocol or simply not described in this record.

The Full Analysis Set is defined as enrolled participants who received at least one dose and had at least one post-baseline UPCR measurement from a 24-hour urine collection. The number included in that analysis is not reported in the registry record. The handling of participants without a post-baseline measurement, those missing a Week 13 measurement, and other incomplete observations is also not reported. No imputation method, sensitivity analysis, or alternative analysis population is described.

These gaps limit assessment of both the estimand and the robustness of any endpoint result. The definition of the Full Analysis Set gives some information about eligibility for analysis, but it does not specify how available observations were modeled or how missing data affected the estimate. No conclusions about the direction or size of potential bias can be drawn from the registry information.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (4.3%), hypervolaemia (4.3%), acute kidney injury (4.3%), renal impairment (4.3%), disease progression (4.2%).

The registry lists serious adverse events for two PF-06730512 dose groups. In the 1000 mg IV group, 2 of 23 participants were affected; in the 300 mg IV group, 2 of 24 were affected. The separate counts for other adverse events are 11 of 23 and 12 of 24, respectively. No deaths are listed in either group. These are participant counts, not rates adjusted for time at risk.

The serious-event terms listed include Diarrhoea, Hypervolaemia, Acute kidney injury, and Renal impairment, each reported as 4.3%; Disease progression and COVID-19 are each reported as 4.2%. The record does not assign these terms to a particular dose group in the information, so group-specific attribution should not be inferred. The percentages and event counts may also refer to different summaries; the record does not explain their relationship.

These figures are descriptive. The non-randomized design and the lack of a like-for-like control group mean that they cannot establish whether an event was caused by treatment or support a direct comparative safety conclusion. The registry record does not report an inferential analysis of these counts.

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

The study was designed to evaluate PF-06730512 in adults with FSGS, with percentage change from baseline in UPCR at Week 13 as the primary endpoint. The registry record also describes safety, tolerability, and pharmacokinetics as study aims and lists multiple secondary outcomes. This describes the questions the study set out to examine; it is not evidence of a particular efficacy or safety result.

The posted information does not include the primary endpoint estimate or its 90% confidence interval. It therefore cannot establish the size, direction, or precision of the Week 13 UPCR change. A decrease in UPCR is described in the registry as potentially associated with improved renal and cardiovascular function, but no such change is reported as a result in the registry record.

The safety counts show that serious adverse events were recorded in both listed dose groups, and the registry lists no deaths in either group. These descriptive observations do not establish a treatment effect, a causal relationship, or a comparative safety advantage. The trial was non-randomized, and the record warns that its arms are not a like-for-like control comparison.

The information also does not establish why the trial was terminated, whether the termination followed a planned decision, or whether the study met its objectives. Those details are not reported in the registry record. No conclusion should be drawn about the reason for termination from status alone.

In short, the record supports a careful account of the study design, endpoint definition, and posted adverse-event counts. It does not provide the outcome data needed to judge efficacy, estimate the primary effect, or assess its statistical precision. The absence of a posted primary result is not itself evidence of benefit, lack of benefit, or harm.

13. Why This Trial Matters Statistically

This trial is statistically notable for the combination of a sequential, adaptive design and non-randomized allocation. Such designs can be useful for evaluating successive cohorts, but interpreting differences between cohorts requires particular care. Cohorts may differ in participant composition or study timing, and without random allocation those differences can complicate attribution of outcomes to dose.

The primary endpoint is a quantitative measure collected at baseline and Week 13, with a least-squares mean and 90% confidence interval specified as the summary. That structure could support an estimate of change and its uncertainty if the results and analysis details were available. In this registry record, the numerical estimate and interval are absent, so the key statistical evidence for the primary question cannot be evaluated.

The study also illustrates why an endpoint definition and an analysis plan are distinct. The record defines the analysis population in broad terms, but does not report the number analyzed, the model specification, or the missing-data approach. It lists 12 outcomes and zero analyses, while a multiplicity strategy is not reported. Those omissions prevent a full assessment of how statistical uncertainty and multiple outcomes were handled.

Finally, descriptive safety counts should not be confused with comparative evidence. The record gives serious and other adverse-event counts for two dose groups, but explicitly notes that they are not a like-for-like control comparison. Statistical interpretation depends not only on observed counts but also on allocation, follow-up, analysis choices, and completeness of reporting. The record makes the design context important, while leaving the primary efficacy result unavailable.

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.

Several trial-specific limitations constrain interpretation. Allocation is recorded as non-randomized, and the registry cautions that the listed arms are not a like-for-like control comparison. As a result, contrasts between the dose groups cannot be treated as randomized estimates of dose effects. The record does not describe an untreated or placebo comparison.

The official title describes an open-label study, whereas the masking entry reports triple masking. The registry record does not reconcile these statements. The cohort descriptions refer to dose 1, dose 2, and an optional dose 3, but do not map those labels to the 1000 mg IV and 300 mg IV groups in the safety information. That mapping is not reported in the registry record.

The study status is terminated, but the reason for termination is not reported. The primary endpoint estimate and confidence interval are also not reported, nor is the number of participants included in the defined Full Analysis Set. No analysis model, missing-data method, multiplicity approach, interim-analysis plan, or original sample-size justification is reported in the registry record.

These are limitations of what can be interpreted from the registry information. They do not establish that a particular procedure was not used; they mean that its use and consequences cannot be assessed from this record. In particular, neither the status label nor the safety counts resolve the missing primary efficacy result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) — NCT03448692.
• Registry record last updated 2024-04-18; status last verified 2024-04.
• Results first posted 2024-04-18.
• 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

NCT03448692 is a Pfizer-sponsored Phase 2 study of PF-06730512 in adults with FSGS. The registry describes 47 enrolled participants and a 24-week adaptive, open-label, sequential-cohort design with non-randomized allocation. The primary endpoint is percentage change from baseline in UPCR based on a 24-hour urine collection at Week 13, summarized as a least-squares mean with a 90% confidence interval.

The record lists the study as terminated, with a start date of 2018-10-15 and a primary completion date of 2023-02-14. It reports descriptive adverse-event counts for PF-06730512 1000 mg IV and PF-06730512 300 mg IV groups, but cautions that the arms are not a like-for-like control comparison. The primary endpoint result, analysis details, reason for termination, and several other key statistical details are not reported in the registry record.