Aurinia Early Urinary Protein Reduction Predicts Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aurinia Early Urinary Protein Reduction Predicts Response (NCT02949973), a na phase 2 study. The primary outcome is Number of Participants With Reduction or Normalization of Urine Protein/Creatinine Ratio (UPCR).

2. Clinical Question

3. Trial Design

This was a Phase 2 exploratory study of voclosporin in participants with active lupus nephritis. The registry lists a single group, allocation as NA, and masking as none. The intervention was oral voclosporin 23.7 mg twice daily in combination with standard of care. Enrollment was 10 participants. The registry lists the study as completed, with a start date of 2015-06 and primary completion in 2016-12.

The study's stated purpose was to assess whether biomarkers measured at 8 weeks could predict clinical response over 24 and 48 weeks. The primary outcome was the number of participants with reduction or normalization of UPCR at 24 weeks, in the Safety Population. Complete remission at Week 24 and Week 48 are listed as secondary outcomes. The registry lists six outcome measures and six analyses, but does not describe the remaining measures or the analysis procedures in the information available for this account.

Because there was no separate control group, this design describes outcomes among participants receiving the intervention; it does not estimate a comparative treatment effect. The allocation and masking entries indicate that the record does not describe random assignment or masking. The registry record does not report a protocol rationale for these design choices, a sample-size justification, or details of how standard of care was administered.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population

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 Number of Participants With Reduction or Normalization of Urine Protein/Creatinine Ratio (UPCR), measured over 24 weeks.

The primary endpoint is a count: the number of participants in the Safety Population who had a reduction or normalization of urine protein/creatinine ratio (UPCR) at 24 weeks. UPCR is a urine-based measure used to quantify protein in relation to creatinine. A change in this measure can be used to describe an aspect of kidney involvement in lupus nephritis. The registry names the endpoint but does not state the threshold, operational definition, or rule used to classify a participant as having a reduction or normalization.

A participant count is a binary-outcome summary: each participant either meets the specified outcome definition or does not. Counts can communicate how many participants met an endpoint, but interpretation also depends on the population assessed and on the denominator. The registry record identifies the Safety Population but does not report the primary count, a denominator for the endpoint result, or an uncertainty interval. The stated timepoint is 24 weeks; the endpoint should therefore be read as a time-specific outcome, not as a complete description of the course of disease or of changes at other times.

The endpoint is clinically relevant to the study's focus on response, but the record does not provide enough detail to determine exactly how its classification was made. Complete remission at Week 24 and Week 48 is listed separately as a secondary outcome, and should not be treated as interchangeable with the primary UPCR outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant-count endpoint, a single-group design, and an exploratory predictive objective. It does not report the statistical methods used to evaluate the primary endpoint or biomarker prediction. The concepts below explain how such data are generally interpreted; they do not describe unreported procedures from this study.

What a participant count represents

For a binary endpoint, each participant is classified according to whether the outcome definition is met. The count is the number classified as meeting it. To interpret that count as a proportion, a denominator is also needed: typically the number of participants assessed for that endpoint. A count alone does not reveal the denominator if the endpoint analysis population differs from the number enrolled or if outcome data are missing. The registry identifies the Safety Population for the primary endpoint, but does not report the endpoint count or the number assessed for it.

Here, the outcome definition concerns reduction or normalization of UPCR at 24 weeks. Such classifications depend on the prespecified rule for what qualifies as a reduction or normalization, including any threshold and handling of measurements. Those details are not reported in the registry record. Without the rule, readers cannot independently determine which participant-level observations would meet the endpoint.

Prediction is different from comparison

Prediction asks whether information measured earlier helps distinguish or estimate later outcomes. In this study, the stated question concerns biomarkers measured at 8 weeks and clinical response over 24 and 48 weeks. A predictive analysis would need to define the biomarkers, the later response outcomes, and the method used to assess how well early measurements correspond to later response. The registry information does not report those details or the resulting estimates.

A predictive association within a treated group is not the same as a treatment effect. A control group is generally needed to compare outcomes under different treatment strategies and to separate treatment-related differences from other explanations. This record describes a single group, with allocation listed as NA, rather than a like-for-like controlled comparison. Any within-group relationship between an early biomarker and later outcome would therefore answer a different question from whether voclosporin changes outcomes relative to a comparator.

Uncertainty and precision

A point estimate is a single summary of the observed data, such as a count or proportion. A confidence interval is a range calculated by a statistical procedure to express the uncertainty associated with an estimate under its assumptions. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision. The registry record does not report a confidence interval for the primary outcome or predictive analyses, so their precision cannot be assessed from the available information.

In small studies, individual observations can have a noticeable influence on summaries and estimates. This makes it especially important to report the denominator, missing observations, outcome definitions, and uncertainty. The enrollment of 10 is reported, but the endpoint-specific numbers assessed and the handling of missing data are not. No p-value or biomarker performance estimate is reported in the registry information.

Planning calculations versus study evidence

Sample-size calculations are planning tools: they describe how many participants might be needed under specified assumptions about an effect, variability, significance level, allocation, and analysis. They are not a measure of the evidence observed in a completed study. A planning illustration based on an observed effect would still depend on assumptions and would not establish that the study had adequate power or that an effect is real. The record does not report the trial's own sample-size justification or a statistical plan, and no study-specific planning estimate can be interpreted as an observed result.

General planning approaches often assume a particular outcome distribution and a particular allocation between groups. Those assumptions matter because departures from them can change the reliability of the calculation. In a single-group study, a calculation that assumes equal allocation between two arms does not describe the design actually listed in the registry. No arm-to-arm sample-size comparison should be inferred from this study's design.

Multiplicity and model choices

When a study evaluates several outcomes, biomarkers, timepoints, or statistical tests, the chance of at least one apparently notable result can increase if no adjustment or prioritization is used. Statistical methods may address this through prespecified primary hypotheses, adjustment procedures, or careful exploratory interpretation. The registry lists six outcome measures and six analyses, but does not report a multiplicity strategy or identify the full analysis set. It is therefore not possible to determine how multiple outcomes or tests were handled.

Model choice also depends on the question, outcome type, sample size, and data structure. For binary outcomes, methods can estimate counts, proportions, or associations; predictive work may use models that relate early measurements to later outcomes. The choice should be justified and reported, including how assumptions were checked. The record does not state which model or tests were used for the primary endpoint or biomarker analyses. Statistical methods cannot be reconstructed from the study title and outcome labels alone.

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("Voclosporin 23.7 mg Twice Daily (BID) in Combinati")
n      <- c(10)
events <- c(7)
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  Voclosporin 23.7 mg Twice Daily (BID) in Combinati  10  7  70.0  34.8  93.3  39.7  89.2  39.0  89.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses, including the primary UPCR outcome and complete remission outcomes at Week 24 and Week 48. It does not report whether outcomes or analyses were prioritized beyond identifying the primary endpoint, how many biomarker hypotheses were assessed, or whether any adjustment for multiple testing was used. Without those details, the possibility of multiplicity-related false-positive findings cannot be evaluated. This matters particularly for an exploratory predictive study, where several biomarkers, outcomes, or timepoints may be considered.

The primary outcome population is identified as the Safety Population. The record does not explain how that population was defined, whether all enrolled participants were included in each outcome analysis, or how participants with missing measurements were handled. The number with available UPCR data at 24 weeks is not reported in the registry record. Missingness can affect a count or proportion if participants without observed outcomes are excluded or classified according to an analysis rule; the rule used in this study is not reported.

It is also not reported whether the study used an intention-to-treat, per-protocol, or other efficacy analysis population. The safety figures list 10 participants at risk, but that does not establish the analysis population used for every clinical or biomarker outcome. The registry record does not describe interim analyses, a prespecified statistical analysis plan, or sensitivity analyses for missing data. These omissions limit assessment of whether the analyses followed prespecified procedures and how robust the reported findings would be to alternative assumptions.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute tonsilitis (10.0%), pneumonia (10.0%), anaemia (10.0%), pleural effusion (10.0%), pyrexia (10.0%).

The safety group is described as receiving voclosporin 23.7 mg twice daily in combination with standard of care. The registry reports 10 participants at risk for serious adverse events, with 3 affected, and reports 10 at risk and 10 affected in the other adverse-event category. It reports 0 deaths. These are participant counts in the registry's safety summary; they are not comparative estimates because no control group is described.

The listed serious-event terms are Acute Tonsilitis, Pneumonia, Anaemia, Pleural effusion, Pyrexia, and Systemic lupus erythematosus, each reported at 10.0%. Those term-level percentages should be kept distinct from the overall count of participants with serious adverse events. The registry information does not explain whether participants experienced more than one listed term, how event terms were coded, or the timing and duration of events.

Serious adverse events are not the same as all adverse events, and a term's appearance in the list does not establish its cause. The record does not provide a comparison that could attribute differences in event frequency to a treatment. These figures describe the safety entries for this group; they do not by themselves establish a causal relationship or permit comparison with another treatment strategy.

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

The study is an exploratory investigation of early biomarkers as possible predictors of later clinical response among participants with active lupus nephritis receiving voclosporin and standard of care. The registry provides the design, enrollment, outcome labels, and selected safety counts. It does not report the primary UPCR outcome count or the biomarker analyses needed to judge predictive performance. The central scientific question therefore cannot be answered quantitatively from the registry information.

The study does not provide a randomized treatment comparison. A single-group result, even if an outcome count were reported, would describe what happened among participants in that group. It would not show what would have happened to comparable participants under a different treatment or no study intervention. The record's design does not support a controlled estimate of a treatment difference.

Nor does the study aim itself establish that an early biomarker is useful for prediction. Evidence for prediction would require reported biomarker values and later outcomes, a clearly stated analysis, and information on uncertainty and performance. Those results and methods are not reported in the registry record. The primary endpoint definition also lacks the threshold or classification rule needed to fully interpret the outcome.

The safety entries are descriptive. The record reports 3 participants with serious adverse events, 10 participants affected in the other adverse-event category, and 0 deaths, with the listed serious-event terms each reported at 10.0%. In the absence of a comparator, these figures cannot establish whether event frequencies differ from those under another approach or establish causation.

In general, statistical interpretation depends on the prespecified question, outcome definition, analysis population, missing-data approach, and uncertainty estimates. Several of these details are not reported in the registry record. Accordingly, the information supports a limited account of the study's purpose and recorded safety data, not a conclusion about clinical benefit, predictive accuracy, or comparative safety.

14. Why This Trial Matters Statistically

This study is statistically notable because its stated goal is prediction rather than only description of a clinical outcome. Measuring biomarkers at 8 weeks and assessing response over 24 and 48 weeks raises questions about whether early measurements contain information about later outcomes. Answering that question requires clear outcome definitions and analyses that relate each early measurement to a later result. The registry describes the aim, but does not report the biomarker-specific findings or methods needed to assess it.

The single-group design also illustrates an important distinction in clinical research. A within-group pattern may be relevant to prognosis or prediction, but it does not estimate a treatment contrast. Without a control group, observed outcomes cannot be separated from changes that might occur for other reasons, including the course of disease or concurrent standard of care. The design is therefore important context for interpreting any outcome counts.

The small enrollment of 10 also makes transparent reporting of denominators and uncertainty especially important. In general, estimates from small groups can be sensitive to the outcomes of individual participants. Reporting endpoint counts, confidence intervals, missing observations, and analysis rules helps readers understand both the magnitude and precision of findings. The registry does not report the primary outcome count or uncertainty estimate.

Finally, this record illustrates why exploratory studies should be distinguished from confirmatory evidence. Multiple outcomes and analyses may be informative for generating hypotheses, but the interpretation depends on how hypotheses were selected and whether multiplicity was addressed. Those procedures are not reported in the registry record. The study's stated purpose is scientifically focused, while the available results information is too limited to assess the predictive question statistically.

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 primary limitation for interpreting efficacy-related results is that the registry record does not report the primary UPCR outcome count. It also does not report the complete-remission counts listed for Week 24 and Week 48. Without these results, the clinical outcomes cannot be quantified or compared across the listed timepoints.

The study is single group, with allocation listed as NA and masking listed as none. No separate comparator group is described. This limits interpretation to outcomes observed in the study group and prevents a like-for-like comparison. The record does not explain why this design was selected or report a protocol justification.

The stated predictive objective cannot be evaluated from the available information because the biomarker-specific measurements, response definitions, statistical procedures, and resulting estimates are not reported in the registry record. The primary endpoint also lacks a reported operational definition, including the threshold used for reduction or normalization of UPCR. The registry identifies the Safety Population but does not describe endpoint-specific denominators or the handling of missing observations.

Enrollment was 10 participants. Such a small group limits the amount of information available for estimating outcome frequencies and evaluating biomarker relationships. No confidence intervals for the primary endpoint or predictive analyses are reported. The record lists six outcome measures and six analyses but does not describe multiplicity procedures, interim analyses, the statistical analysis plan, or the sample-size justification.

The safety summary is also limited: it does not give event timing, duration, participant-level overlap among serious-event terms, or a control-group comparison. The registry reports selected counts and terms, but those entries alone cannot establish causation or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Aurinia Early Urinary Protein Reduction Predicts Response — NCT02949973.
• Registry record last updated 2021-03-19; status last verified 2021-03.
• Results first posted 2021-03-19.
• 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

NCT02949973 is a completed Phase 2 exploratory, single-group study of oral voclosporin 23.7 mg twice daily in combination with standard of care for active lupus nephritis. Enrollment was 10. The study's stated aim was to assess whether biomarkers measured at 8 weeks predicted clinical response over 24 and 48 weeks.

The primary outcome was the number of participants with reduction or normalization of UPCR at 24 weeks in the Safety Population. Complete remission at Week 24 and Week 48 was listed as a secondary outcome. The primary outcome count and biomarker-specific results are not reported in the registry record.

The registry reports 3 participants with serious adverse events, 10 affected in the other adverse-event category, and 0 deaths. Six serious-event terms are listed at 10.0% each. No control group is described, and the record does not report the statistical plan, missing-data procedures, or multiplicity approach.