AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV) (NCT02141672), a randomized phase 2 study. The primary outcome is Number of Subjects Achieving Complete Renal Remission at 24 Weeks.

2. Clinical Question

This is a question about a binary clinical outcome: each participant is classified as achieving or not achieving complete renal remission under the registry definition. The planned comparison involves two active regimens and a placebo group, but the record information does not give the remission counts, proportions, confidence intervals, or a primary comparison’s statistical test. The study therefore cannot be interpreted from these details as demonstrating a particular size or direction of difference.

The clinical question also depends on the operational definition of remission. Participants had to meet the stated protein/creatinine and kidney-function criteria, and specified rescue treatment or prednisone use counted as failure to achieve remission. Those rules make the outcome more specific than a general judgment of improvement. They also mean the result, if reported, would apply to this combined definition rather than to every possible definition of renal response.

3. Trial Design

The registry identifies AURA-LV as a randomized, phase 2, parallel-group study with quadruple masking. It lists an enrollment of 265 and names three groups: voclosporin low dose, voclosporin high dose, and placebo. The record does not describe which people or roles were included in the quadruple masking label, nor does it provide further details about the randomization procedure or allocation concealment.

The low-dose regimen is oral voclosporin at 23.7 mg BID. The high-dose regimen begins with oral voclosporin at 23.7 mg BID until week 2, then uses 39.5 mg BID. The placebo descriptions list 3 capsules BID for the low-dose schedule, and 3 capsules BID until week 2 followed by 5 capsules BID for the high-dose schedule. The record does not provide further details about how treatment adherence was assessed or how dose changes were handled.

The stated primary outcome is the number of participants achieving complete renal remission at week 24. The study summary describes the objective as assessing the efficacy of two doses compared with placebo in achieving complete remission after 24 weeks of therapy. Listed secondary outcomes cover complete remission at week 48, remission in the presence of low-dose steroids, time to complete remission, sustained early complete remission, partial remission, and remaining in complete remission.

The registry lists a start date of 2014-06, primary completion of 2016-07, and a completed status. These details identify the study’s broad design and timeline, but do not establish the exact analysis plan, follow-up completeness, or the results of any group comparison. Those details are not reported in the registry record summarized for this analysis.

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: Eligible subjects were randomized in a ratio of 1:1:1 to receive either voclosporin 23.7 mg BID or 39.5 mg BID, or matching placebo for 48 weeks. All subjects were also to receive 2 g/day MMF. In addition, all subjects were to receive 0.5 g/day IV methylprednisolone on Days 1 and 2 before changing to a reducing course of oral corticosteroid therapy on Day 3.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat

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 Subjects Achieving Complete Renal Remission at 24 Weeks, measured over week 24.

The primary endpoint counts participants achieving complete renal remission at week 24. The record defines remission using two requirements: a confirmed protein/creatinine ratio of ≤0.5 mg/mg, and either eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. It further classifies participants who received lupus nephritis rescue medication, or prednisone above the specified limits, during the stated period as not achieving complete remission.

This endpoint is used to represent a defined state of renal response rather than a single laboratory change. Combining proteinuria and kidney-function criteria requires participants to meet both parts of the definition, while the treatment-related failure rules make the classification sensitive to rescue treatment and specified steroid use. These rules matter when interpreting any reported count: the count reflects the full registry definition, not simply the number with a lower protein/creatinine ratio.

In general, a binary endpoint is straightforward to describe as a count or proportion in each group. It does not, by itself, show how close participants who did not meet the full definition came to remission, or how their individual measurements changed. The record identifies the primary population as intent to treat. It does not report the primary outcome counts or the numerical comparison, so the degree of remission in each group and the precision of any difference cannot be assessed from the information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-group trial. In general, randomization aims to make assigned groups comparable at the point of allocation, on average, with respect to both measured and unmeasured baseline characteristics. It does not guarantee that every group will look identical, especially in an individual trial. The record does not describe the sequence-generation method, allocation concealment, or any stratification factors, so those procedural features cannot be evaluated from the information.

The record labels masking as quadruple. Masking is generally intended to reduce the influence of treatment knowledge on care, participant reporting, outcome assessment, or analysis. The label alone does not identify which roles were masked or how masking was maintained. Those details are not reported in the registry record. The study is also described as parallel-group, meaning the listed regimens are assigned as separate groups rather than as a planned sequence of treatments within each participant.

The primary outcome is binary. Each participant either meets the complete-remission definition at week 24 or is classified as not achieving it. In general, binary outcomes can be analyzed using counts, proportions, risk differences, relative measures, or regression models. These methods answer related but not identical questions. A difference in proportions expresses an absolute contrast; a relative measure expresses one group’s outcome in relation to another. The registry information does not state which measure or model was used for the primary comparison, and it does not provide the numerical results needed to interpret one.

A confidence interval is a way to describe statistical uncertainty around an estimate. In general, a narrow interval indicates greater precision than a wide interval, while an interval spanning a range of plausible values may leave substantial uncertainty about the magnitude or direction of an effect. A confidence interval is not a guarantee that the true value lies within the reported limits. No primary-outcome confidence interval is reported in the registry information, so precision cannot be assessed.

For a binary outcome, the denominator matters as much as the count. A count alone does not show the event frequency unless the number of participants included in the analysis is also known. The registry identifies the primary population as intent to treat, but does not give the primary endpoint counts or analysis denominators in the information. The enrollment figure is not a substitute for the endpoint-specific denominator: participants may have different availability of outcome measurements, and the record does not describe missing-assessment handling.

The endpoint definition includes two clinical measurement criteria and rules concerning rescue medication and prednisone use. In general, such rules make the endpoint reproducible by specifying how a participant is classified. They also create a composite decision: failure on any required criterion can prevent classification as complete remission. Interpretation should therefore focus on the exact rule rather than treating remission as interchangeable with improvement in one measure. The record does not report component-level results that would show which criterion most often determined classification.

Time-to-event outcomes appear among the secondary outcomes, including time to complete remission and time to partial remission. In general, time-to-event methods account for both the timing of an event and the fact that some participants may not have an observed event by the end of follow-up. A hazard ratio or a survival curve can describe such data, but interpretation depends on assumptions and on how censoring is handled. The registry information lists these outcomes but does not report their analysis methods, estimates, censoring rules, or results.

The study has three treatment groups, and the outcome list contains multiple endpoints and time points. In general, testing several comparisons increases the chance of at least one apparently unusual result if each is judged separately without an adjustment or a prespecified testing hierarchy. The registry information does not report whether multiplicity was controlled, which comparisons were primary for testing, or whether any analyses were exploratory. Statistical significance for an isolated comparison, if reported elsewhere, would need to be interpreted in light of those choices.

Over-dispersion is a general issue for count outcomes when observed variability exceeds what a chosen simple probability model assumes. It can make standard errors too small if the model does not allow for the extra variability. The primary endpoint is described as a participant count for a binary remission outcome, not as a rate of recurrent events. The record does not report a model or evidence of over-dispersion; this general concept should not be read as a feature established for this trial.

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are not observed power and do not establish that the original trial was designed with those assumptions. The registry record does not report the trial’s own sample-size justification or design assumptions in the information. The illustrations are hypothetical calculations, not trial outcomes or evidence about the likelihood of a result.

Finally, statistical significance and clinical importance are distinct concepts. In general, a small estimated difference can be statistically detectable in a sufficiently precise study, while an estimate with substantial uncertainty may not rule out effects in more than one direction. The registry information does not provide an effect estimate or its uncertainty for the primary outcome, so neither statistical strength nor clinical magnitude can be evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome and a set of secondary outcomes spanning different time points and forms of response. It does not report a multiplicity adjustment, a hierarchical testing plan, or a distinction between confirmatory and exploratory secondary analyses in the information. When multiple outcomes or group comparisons are tested, the chance of a false-positive finding across the set can increase. In general, prespecifying a testing order or adjusting for multiple comparisons can help control that risk, but the method used in this study is not reported in the registry record.

The primary population is identified as intent to treat. The registry information does not state how missing week-24 remission assessments were handled, whether imputation was used, or how participants who discontinued assigned treatment were classified. It also does not provide the number with an observed endpoint in each group. These details matter because missing outcome data can affect both the analysis denominator and the interpretation of a group comparison.

The record does not report the statistical analysis plan, the exact model used for the primary endpoint, or whether any covariate adjustment was applied. It also does not report interim analyses or stopping rules. These are unknowns, not evidence that such procedures were or were not used. Without the plan and outcome data, readers cannot assess whether the analyses followed prespecified methods or how sensitive results might be to alternative assumptions about missing data and multiplicity.

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: pneumonia (5.6%), renal failure acute (4.5%), gastroenteritis (2.3%), sepsis (2.3%), posterior reversible encephalitis syndrome (2.3%).

The registry lists serious adverse events affecting 25 participants at risk of 89 in the low-dose group, 22 at risk of 88 in the high-dose group, and 14 at risk of 88 in the placebo group. It also lists deaths: 10 in the low-dose group, 2 in the high-dose group, and 1 in the placebo group. These are recorded counts, not estimates of treatment causation. The registry information does not report a comparative safety model, the timing of the events, or an assessment attributing events to study treatment.

Other adverse events are listed for 82 participants at risk of 89 in the low-dose group, 85 at risk of 88 in the high-dose group, and 75 at risk of 88 in the placebo group. Serious-event terms listed among the most frequent include pneumonia at 5.6%, acute renal failure at 4.5%, gastroenteritis at 2.3%, sepsis at 2.3%, posterior reversible encephalitis syndrome at 2.3%, and systemic lupus erythematosus at 2.3%.

In general, adverse-event counts should be read with their denominators and reporting definitions. They do not establish that a treatment caused an event, and different event counts do not by themselves establish a statistically reliable group difference. The registry information does not state the adverse-event observation period or provide adjusted comparisons.

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

The registry record describes a randomized comparison of two voclosporin regimens with placebo in active lupus nephritis, and it specifies complete renal remission at week 24 as the primary outcome. This establishes what the trial set out to examine and how remission was defined. It does not, in the information, supply the primary outcome results needed to judge whether the groups differed or how large any difference was.

A study design is not itself a finding. Randomization and masking describe methods intended to support fair comparison and reduce bias; they do not guarantee an unbiased or precise estimate. The record’s enrollment and treatment descriptions do not reveal the actual remission outcome in each group. Nor can the listed secondary outcomes be treated as evidence of a particular result when their numerical findings are not reported in the registry information.

Even when an effect estimate is available, it needs to be read together with its uncertainty, analysis population, endpoint definition, and missing-data handling. In general, a confidence interval helps show which effect sizes remain compatible with the observed data under the model, while a point estimate alone can create a misleading impression of certainty. For this trial’s primary comparison, the registry entries provide no estimate or interval to assess.

The serious adverse-event data are descriptive counts. They do not show that an event was caused by a study drug, and they do not provide a complete comparison of potential benefits and harms. The record information also does not provide the timing, attribution, or adjusted analyses needed for a fuller safety interpretation.

Accordingly, the available registry information supports a description of the design, outcome criteria, and recorded safety counts, but not a conclusion about efficacy or a definitive comparative safety judgment. Any interpretation should remain bounded by the reported data and the specific remission definition rather than extending to other outcomes or populations.

13. Why This Trial Matters Statistically

This trial is statistically notable for posing a three-group question with two active regimens and a placebo comparator, while using a defined binary primary outcome at a specified follow-up time. That structure requires clarity about which treatment contrasts are central, how the remission outcome is classified, and how the multiple secondary questions are handled. The registry record names these elements but does not report the detailed analysis plan or primary numerical results in the information.

The endpoint illustrates how a clinical outcome can combine laboratory criteria, kidney-function criteria, and treatment-use rules. Such a definition can improve consistency by making classification explicit. At the same time, it means that a single remission count conceals the different pathways by which participants may or may not meet the criteria. Component-level results, if available, could help explain the outcome; they are not reported in the registry information.

The study also highlights a central distinction in trial interpretation: design features and results answer different questions. Randomization, parallel groups, and masking describe how the comparison was organized. They do not reveal the magnitude or precision of an outcome contrast. A complete statistical interpretation needs group results, a clearly identified comparison, and uncertainty measures, none of which are reported for the primary endpoint in the information.

Finally, the record’s multiple secondary outcomes and three treatment groups make multiplicity and analysis-population details relevant. Knowing how outcomes were prioritized and how missing observations were handled would help readers judge the strength and scope of any reported findings. Those details are not reported in the registry information, so the main statistical lesson is the importance of separating what the design specifies from what the results establish.

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 of the registry information is that it does not report numerical results for the primary endpoint. Without group-specific remission counts, denominators, effect estimates, confidence intervals, or a test result, the primary comparison’s direction, magnitude, and precision cannot be evaluated. The outcome definition is detailed, but a definition is not an observed result.

The record identifies intent to treat as the primary population but does not explain missing outcome handling, analysis denominators, treatment discontinuations, or protocol deviations. The randomization and masking labels are present, but implementation details are not reported in the information. The exact statistical model, covariate adjustment, and prespecified comparison structure are likewise not reported.

Multiple time points and secondary outcomes are listed, yet the record information does not describe multiplicity control or distinguish confirmatory from exploratory analyses. The sample-size assumptions concern planning illustrations based on an observed effect; they do not supply the original trial’s design justification or observed power. No sample-size rationale for the trial is reported in the registry record.

The safety data are limited to recorded counts and selected serious-event terms. The registry information does not provide event timing, causal attribution, comparative inference, or the observation period. These limitations constrain interpretation of both efficacy and safety and should not be replaced by assumptions about unreported methods or results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV) — NCT02141672.
• Registry record last updated 2021-05-18; status last verified 2021-04.
• Results first posted 2021-05-18.
• 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

AURA-LV (NCT02141672) is listed as a completed, randomized, phase 2, quadruple-masked, parallel-group study sponsored by Aurinia Pharmaceuticals Inc. The registry gives an enrollment of 265, a start date of 2014-06, and primary completion of 2016-07.

The study compared oral voclosporin at 23.7 mg BID, a regimen that increased from 23.7 mg BID to 39.5 mg BID after week 2, and placebo. The primary outcome was the number of participants achieving complete renal remission at week 24, in an intent-to-treat population. The remission definition combines protein/creatinine and eGFR criteria with rules for rescue medication and specified prednisone use.

The registry information does not report numerical primary-outcome results, the primary comparison estimate, or its uncertainty. It lists secondary outcomes and serious adverse-event counts, but does not provide the analysis details needed for a full comparative interpretation.