PR3-AAV Resilient Remission or PRRR: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PR3-AAV Resilient Remission or PRRR (NCT05376319), a randomized phase 2 study. The primary outcome is Number of Patients to Achieve Both Complete Remission and Seronegativity for ANCA..

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, double-blind, parallel-group study with an active comparator. It compared obinutuzumab with rituximab in participants with PR3-associated ANCA vasculitis and a clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis. The sponsor was Mayo Clinic. The registry lists an enrollment of 6.

The study started on 2023-06-30, and the primary completion date is listed as 2024-05-07. Its status is terminated. The registry explains that the study was terminated because of lack of funding and that data were not collected or analyzed for some participants for that reason. These circumstances matter when interpreting the reported outcome: the small number assessed and the missing outcome information limit what can be learned from the comparison.

Participants were assigned to an intravenous obinutuzumab arm or an intravenous rituximab arm. Each arm description specifies two doses of the assigned drug. The registry does not report the dose amounts, infusion timing, allocation ratio, sequence generation method, or details about how double blinding was maintained. It also does not report further information about eligibility criteria or the statistical analysis plan.

The primary outcome was a count of participants who achieved both complete remission and a negative PR3-ANCA test at 6 months. Secondary outcomes concerned sustained complete remission at 6 months, 12 months, and 18 months. The registry lists four outcome measures, but no analyses are posted. The reported primary counts are 0 in the obinutuzumab arm and 0 in the rituximab arm, with one participant in each arm reaching the 6-month assessment. Those counts should be read alongside the stated lack of outcome data for other participants, not as a complete account of outcomes for everyone enrolled.

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: Terminated study due lack of funding. Data was not collected nor analyzed due to lack of funding. Only one subject in each arm reached 6 months. Data was not collected nor analyzed for 1 subject in the Intravenous dose of obinutuzumab and 3 subjects in the Intravenous dose of rituximab.

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 Patients to Achieve Both Complete Remission and Seronegativity for ANCA., measured over 6 months.

The primary endpoint is a participant count for a combined clinical and laboratory outcome at 6 months. A participant had to meet both parts: complete remission and ANCA seronegativity. The registry defines complete remission as a BVAS/WG score of 0 without glucocorticoids beyond the prescribed prednisone taper. Seronegativity is defined as a negative test for antibodies directed against serine proteinase 3, meaning a negative PR3-ANCA assay.

Using both components makes the endpoint more specific than counting either clinical remission or a negative assay alone. It asks whether the clinical disease activity measure and the antibody test were both consistent with the defined outcome at the assessment time. This kind of combined endpoint can be useful when a trial aims to assess more than one aspect of disease status. However, the interpretation depends on the exact definitions, timing, and completeness of the assessments.

The registry reports a count of 0 in each arm. Only one subject in each arm reached the 6-month assessment, and the record says outcome data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm. The registry does not report endpoint values for those participants. The small number assessed and the missing outcome information therefore make the count an incomplete basis for judging the comparative result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: a participant either met both endpoint criteria at the 6-month assessment or did not. The reported result is a count of participants with the event, rather than a continuous measurement such as a laboratory value. The registry lists 0 participants with the combined outcome in each arm. It does not report a dispersion measure for this endpoint, which is not generally used to describe a simple event count.

What does a treatment comparison estimate?

In general, a comparative analysis of a binary outcome can estimate how often an event occurs in each treatment group and quantify the contrast between those groups. Depending on the statistical plan, that contrast may be expressed using a difference, ratio, or another measure. Each estimate should be accompanied by an assessment of uncertainty, commonly a confidence interval. The registry record does not report a comparative estimate, a confidence interval, or a p-value for this outcome. No new treatment contrast can be reliably recovered from the posted information alone.

Here, both posted counts are zero, and the arm summaries each list one participant. With so few observations, the data offer little information about the range of event frequencies that could occur in a larger study. In general, sparse binary outcomes can make standard approximations unreliable. Exact or otherwise suitable methods may be considered when event counts are small, but the registry does not report which method, if any, was used. It also lists no analyses.

Why does the number assessed matter?

The observed count must be interpreted with its assessment population. The registry says only one subject in each arm reached 6 months. It also states that outcome data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm. The record does not give endpoint classifications for those participants. An analysis restricted to assessed participants and an analysis that includes all randomized participants under a specified missing-data rule can answer different questions. The analysis population and missing-data method are not reported in the registry record.

In general, missing outcomes can reduce precision and can introduce bias if the chance of being missing is related to the outcome or differs between treatment groups. The record attributes the missing data to lack of funding, but it does not establish what the unobserved outcomes would have been. No imputation method, sensitivity analysis, or other approach to missing outcomes is reported. It is therefore not possible to determine how the missing information would affect a treatment estimate.

What can a confidence interval contribute?

In general, a confidence interval presents a range of values compatible with an estimate under a stated statistical model and method. It helps distinguish a precise estimate from one that remains uncertain. It does not guarantee that the true effect lies within the interval, and it does not correct for missing data or bias. No confidence interval is posted for the primary comparison. With the sparse observed counts and missing outcome information, the record provides no quantified precision for a treatment contrast.

How should the planning assumptions be read?

The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence about the study’s actual design or its observed power. Sample-size illustrations are used to explore how much information a future study might need under specified assumptions; they do not show the probability that this terminated study detected an effect.

The registry record does not report numerical planning estimates or the particular fraction of the observed effect used for each illustration. It also does not report a prospective sample-size justification for this trial. The posted planning assumptions should therefore not be confused with a documented protocol calculation or with analyses of the trial’s results.

Why does over-dispersion matter?

In general, over-dispersion arises when observed variability exceeds what a chosen statistical model expects. It is important for some count outcomes, where treating the data as less variable than they are can make uncertainty appear too small. The primary endpoint is reported as a participant count for a binary outcome, with no dispersion measure. The registry does not report a model for over-dispersion or an analysis that addresses it. There is no basis in the record for claiming that over-dispersion was tested or found.

The secondary outcomes are counts of participants achieving sustained complete remission at 6 months, 12 months, and 18 months. The registry lists these outcomes but reports no analyses. The record also does not specify the statistical procedures planned for those measures, how repeated assessments were to be handled, or whether adjustment for multiple comparisons was planned. Without those details and without posted analyses, the secondary outcomes cannot be used to infer a treatment effect.

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("Intravenous Dose of Obinutuzumab", "Intravenous Dose of Rituximab")
n      <- c(1, 1)
events <- c(0, 0)
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  Intravenous Dose of Obinutuzumab  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Intravenous Dose of Rituximab  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: the number of patients achieving sustained complete remission at 6 months, 12 months, and 18 months. It also lists four outcome measures overall and no analyses. The record does not report whether a single secondary outcome was designated as most important, whether a testing sequence was planned, or whether any adjustment for multiple comparisons was intended. Those details are not reported in the registry record.

In general, examining multiple outcomes or assessment times creates more opportunities for a chance finding. A prespecified multiplicity strategy can control how strongly statistical evidence is interpreted across several comparisons. Without a reported strategy or posted analyses, no multiplicity-adjusted conclusion can be drawn from the listed secondary outcomes. They should be treated as outcomes named in the record, not as corroborating evidence for the primary comparison.

Missing primary outcome information is a central limitation. The registry states that only one subject in each arm reached the 6-month assessment and that data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm because of lack of funding. It does not report the outcomes for those participants or describe an approach for handling missing results. The analysis population, including whether any intention-to-treat or per-protocol population was used, is not reported in the registry record.

In general, an analysis population definition identifies which participants contribute to a particular estimate and under what rules. A missing-data strategy explains how unavailable outcomes are addressed and what assumptions are made. Neither is reported for this study. No sensitivity analyses are posted to show how conclusions might change under alternative assumptions about missing outcomes. As a result, the reported counts are descriptive of the participants summarized in the arm results and do not resolve outcomes for everyone enrolled.

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: sepsis (50.0%).

The registry reports serious adverse events for two groups. In the obinutuzumab group, 1 of 2 participants at risk was affected by a serious adverse event; in the rituximab group, 0 of 4 participants at risk were affected. For other adverse events, it reports 2 of 2 participants at risk affected in the obinutuzumab group and 4 of 4 in the rituximab group. Deaths are reported as 0 in both groups. These are small group counts and should be read as descriptive figures, not as stable estimates of comparative safety.

The serious adverse event term listed most prominently is sepsis, at 50.0%. The registry does not specify in the record whether this percentage uses participants, events, or another denominator, so it should not be converted into an event count or attributed to a particular arm. The small safety groups, the terminated status, and the limited outcome information constrain interpretation. The registry record does not report a formal statistical comparison of adverse events. The figures do not establish that one treatment has a safer profile than the other.

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

The result means that the registry reports no participants in either arm meeting the combined primary endpoint among those represented in the primary arm summaries. Each arm summary lists one participant, and the record says only one subject in each arm reached the 6-month assessment. The record also states that outcome data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm because of lack of funding.

This is not evidence that the treatments have identical effects. The zero counts do not establish that the endpoint is unattainable, nor do they show that either treatment is ineffective. They are observations from a very limited assessment, with additional outcome information unavailable. The registry does not report an effect estimate, confidence interval, p-value, or analysis that could quantify how much the groups might differ.

In general, a randomized, double-blind comparison is designed to reduce some sources of bias when comparing treatments. Those design features cannot compensate for having very little outcome information or for missing assessments. Randomization and blinding are reported, but details about the procedures are not reported in the registry record. The terminated status and stated lack of funding help explain the incomplete evidence; they do not allow the missing results to be inferred.

The secondary outcomes are sustained complete remission at 6 months, 12 months, and 18 months. They are listed without posted analyses, so they do not provide additional results for interpreting treatment differences. Similarly, the safety counts are descriptive and based on small groups. They do not support a broad conclusion about comparative safety.

The appropriate statistical reading is therefore narrow: the posted primary counts are 0 in each arm, while the comparative effect and its precision remain undetermined in the registry record. The result cannot establish equivalence, superiority, or absence of benefit. It records a limited set of observed outcomes from a study that ended before the registry reports complete outcome collection and analysis.

14. Why This Trial Matters Statistically

This study matters statistically because its record illustrates the difference between a planned comparison and the evidence that ultimately becomes available. It was designed as a randomized, double-blind, active-comparator study, but it was terminated for lack of funding. The registry reports a very limited primary outcome assessment and says that data were not collected or analyzed for other participants. The design alone cannot supply information that was not observed.

The endpoint also combines a clinical remission definition with a laboratory criterion. Such a combined measure can represent multiple aspects of disease status, but its interpretation relies on clearly defined criteria and complete assessment at the specified time. The record supplies the definitions and reports counts, yet the small number assessed leaves little information about the comparative result. No inferential analyses or precision estimates are posted.

For biostatisticians and clinical researchers, the record underscores why event counts, assessment denominators, missing outcomes, and analysis populations need to be read together. A zero in each arm is not equivalent to a demonstrated absence of difference. Nor does an identical observed count mean the treatment effects are identical. Without adequate outcome information and a reported analysis, the uncertainty cannot be resolved statistically.

The registry also lists secondary outcomes at multiple follow-up times without analyses or a reported multiplicity strategy. This makes it especially important to distinguish outcomes named in a record from results that can support a conclusion. The study offers a useful example of how termination and incomplete data limit the questions that a randomized design can answer, even when the endpoint and treatment comparison are specified.

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 main limitation is the very small number of participants represented in the primary outcome summaries. The registry lists an enrollment of 6, but only one subject in each arm reached the 6-month assessment. Outcome data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm because of lack of funding. The record does not provide endpoint classifications for those participants.

The study was terminated, and no analyses are posted. There is no reported comparative effect estimate, confidence interval, p-value, or description of the inferential method. The registry does not report the analysis population, how missing outcomes were handled, or sensitivity analyses addressing missing data. It is therefore not possible to assess how the unavailable outcomes might influence a comparison.

Although the study is described as randomized and double-blind, the registry record does not report the allocation ratio, randomization procedure, concealment method, or details of how blinding was maintained. Dose amounts and infusion timing are not reported. The record also does not report a prospective sample-size justification or a statistical analysis plan.

The secondary outcomes are listed but have no posted analyses. Multiplicity handling is not reported. Safety information is also limited: the groups at risk are small, the serious adverse event counts are descriptive, and the denominator for the listed sepsis percentage is not specified in the record. These limitations restrict both the comparative efficacy interpretation and the conclusions that can be drawn from the safety figures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PR3-AAV Resilient Remission or PRRR — NCT05376319.
• Registry record last updated 2026-05-06; status last verified 2026-04.
• Results first posted 2024-07-31.
• 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

The registry describes a phase 2 randomized, double-blind, parallel-group study comparing two intravenous doses of obinutuzumab with two intravenous doses of rituximab in PR3-associated ANCA vasculitis. The listed enrollment is 6. The study was sponsored by Mayo Clinic, started on 2023-06-30, and has a primary completion date of 2024-05-07. Its status is terminated because of lack of funding.

The primary endpoint counted participants achieving both complete remission and ANCA seronegativity at 6 months. The registry reports 0 in each arm, with one participant listed in each arm summary. It says only one subject in each arm reached 6 months and that data were not collected or analyzed for one subject in the obinutuzumab arm and three subjects in the rituximab arm. No analyses are posted. The record lists sustained complete remission outcomes at 6 months, 12 months, and 18 months, but does not report their results. The available information is descriptive and does not establish a comparative treatment effect.