Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA (NCT03712345), a randomized phase 2 study. The primary outcome is Number and Percentage of Participants With at Least One TEAE Per Treatment Group..

2. Clinical Question

The study asks whether adding either of two IFX-1 dose regimens to standard care is associated with a different safety profile from adding placebo for participants with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Its primary measure is the number and percentage of participants who experienced at least one treatment-emergent adverse event (TEAE) by Week 24. The record also lists clinical response and remission among secondary outcomes, but does not post inferential analyses for them.

3. Trial Design

This was a Phase II, randomized, double-blind, placebo-controlled, parallel-group study of IFX-1 added to standard care in GPA and MPA. The registry identifies the masking as triple, but does not specify which roles were masked. The three listed groups were IFX-1 high dose, IFX-1 low dose, and placebo. The study title and brief summary frame the investigation around safety and tolerability, with efficacy measures also listed among the outcomes.

The enrollment field is 20. The primary outcome results list 6 participants in the high-dose group, 7 in the low-dose group, and 6 in the placebo group. The record does not explain the relationship between the enrollment field and the group counts reported for this outcome. The study is marked terminated. Its recorded start date is 2018-10-15, and the primary completion date is 2020-09-10; the reason for termination is not reported in the registry record.

The primary outcome is assessed at Week 24 in the Safety Analysis Set. The record lists seven secondary outcomes, including clinical response, clinical remission defined as BVAS = 0, IFX-1 concentration, C5a plasma concentration, and IFX-1 blocking activity at two listed concentrations. These outcomes indicate that the study included clinical and laboratory measures, but the registry record does not post analyses for them. Details such as the randomization procedure, allocation ratio, treatment duration, and specific dose levels are not reported in the registry record.

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 Analysis Set

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

6. Primary Endpoint

The registry lists the primary outcome as Number and Percentage of Participants With at Least One TEAE Per Treatment Group., measured over Week 24.

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event by Week 24, separately for each treatment group. A TEAE is an adverse event that arises or is recorded as treatment-emergent during the study; the registry description does not give further operational criteria for classifying events. The measure is stated as both a number and a percentage, and its analysis population is the Safety Analysis Set.

Counting participants with at least one event gives a participant-level summary of whether any qualifying event occurred. This is useful for describing the breadth of adverse-event experience across groups, while not conveying the number of events per participant, their duration, or their severity. Serious adverse events are a separate safety category and should not be treated as interchangeable with all TEAEs.

The posted primary outcome values are counts: 6 in the IFX-1 high-dose group, 7 in the IFX-1 low-dose group, and 5 in the placebo group. The corresponding listed group sizes are 6, 7, and 6. Although the endpoint title refers to percentages, per-group percentages are not posted as primary outcome values in the registry record. No inferential comparison, confidence interval, or analysis estimate is available, so the counts describe the observed groups without establishing the precision of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome: whether each participant experienced at least one TEAE by Week 24. A binary outcome has two participant-level states for this purpose: the event was recorded, or it was not. The posted results give the number of participants with the event in each group. The endpoint description also refers to percentages, but per-group percentages are not posted as primary outcome values in the registry record.

What do the counts describe?

A count gives the number of participants meeting the endpoint definition. It is not the same as a count of all adverse-event occurrences, because one participant may experience more than one event while still contributing once to a measure of participants with at least one event. The registry defines the primary outcome in participant terms. It does not provide detail about how repeated events, event onset, or event attribution were handled beyond the stated TEAE definition.

The group sizes matter when interpreting counts: the posted primary results list 6 participants for IFX-1 high dose, 7 for IFX-1 low dose, and 6 for placebo. Small group counts make the observed data especially limited as a basis for precise comparisons. General statistical principle: estimates from limited samples tend to be less precise than estimates based on larger samples, and a small change in the observed data can have a noticeable effect on a proportion. No confidence intervals or other uncertainty estimates are reported for these results.

What would a confidence interval add?

General explanation: a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. For a difference between event proportions, it would indicate a range of values compatible with the observed data and the method’s assumptions. A narrow interval would indicate greater precision than a wide interval. The registry record reports no interval for the primary outcome, so the precision of any group contrast cannot be read from the posted counts alone.

Why does the absence of an inferential comparison matter?

The registry lists no analyses for the outcome results. In particular, it does not report a model, test statistic, p-value, confidence interval, or adjusted treatment estimate. A numerical contrast calculated from summary counts would be an unadjusted re-calculation, not a sponsor analysis. Because the record does not post an inferential analysis, no such contrast should be mistaken for a prespecified or adjusted result. General explanation: an inferential comparison uses a statistical model or test to quantify how compatible observed group differences are with a null hypothesis, given assumptions about the design and data. The result depends on the method and cannot be recovered fully from the counts alone when analysis details and participant-level data are absent.

The record describes randomized, triple-masked, parallel groups, but does not give the randomization procedure or the roles covered by masking. Random allocation is generally intended to reduce systematic differences between groups at baseline. Masking is generally intended to reduce the influence of treatment knowledge on care, reporting, or assessment. Those are general design purposes; the registry record does not establish whether they were fully achieved in this trial.

How should planning calculations be understood?

General explanation: sample-size planning uses assumptions about the outcome, the effect a study aims to detect, the significance level, and the desired power. A planning illustration based on an observed effect is not the study’s original design justification and is not observed power. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm; for time-to-event outcomes, it is total events. These assumptions do not substitute for a statistical plan, and the registry record does not report the trial’s original sample-size justification.

For this binary endpoint, general considerations include the number of participants in each group and the event proportion in each group. Over-dispersion is more directly relevant to count outcomes whose variability exceeds a model’s expected variance; it can make standard errors too small if ignored. It is not a reason to treat this participant-level binary endpoint as an event-rate analysis. No model or dispersion adjustment is reported for the primary endpoint.

The record gives a named Safety Analysis Set for the primary outcome, but does not describe its membership rules. It also does not report how missing data were handled, whether any sensitivity analyses were conducted, or whether interim analyses were planned. Those methodological details affect how results could be evaluated, and cannot be inferred from the design label or outcome counts.

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("IFX-1 High Dose", "IFX-1 Low Dose", "Placebo")
n      <- c(6, 7, 6)
events <- c(6, 7, 5)
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  IFX-1 High Dose  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  IFX-1 Low Dose  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Placebo  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety outcome and seven secondary outcomes. The secondary measures include clinical response, clinical remission, IFX-1 concentration, C5a plasma concentration, and blocking activity measures. When multiple outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately. General statistical practice may address this through prespecified outcome hierarchies or multiplicity adjustments, but the registry record does not report whether either approach was planned or used.

No analyses are listed for the posted outcomes. The record therefore does not show which secondary outcomes were analyzed, what statistical methods were used, or whether any multiplicity adjustment was applied. It also does not report interim analyses or stopping rules. No assumptions about those procedures can be drawn from the randomized, masked design.

The primary outcome specifies the Safety Analysis Set, but the membership criteria for that set are not reported in the registry record. The record does not state how missing primary endpoint data were handled, whether every participant in the listed groups had an observed Week 24 assessment, or whether participants were analyzed according to randomized assignment. The registry enrollment field and the group counts for the primary outcome are not explained in relation to one another.

These omissions matter because the population included in an analysis and the handling of unavailable outcomes can affect the estimate and its uncertainty. Without a reported missing-data approach, analysis population definition, or inferential results, the posted counts should be interpreted as descriptive registry results rather than as a complete statistical evaluation of the trial.

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: covid-19 pneumonia (16.7%), atrial fibrillation (16.7%), myocardial infarction (16.7%), anaemia (16.7%), asthenia (16.7%).

The registry lists serious adverse events for 2 participants in the IFX-1 high-dose group, 1 in the low-dose group, and 0 in the placebo group. The listed numbers at risk are 6, 7, and 6, respectively. It also lists other adverse events for 6, 7, and 5 participants in those groups. No deaths are recorded in the listed groups.

The serious-event terms listed are COVID-19 pneumonia, atrial fibrillation, myocardial infarction, anaemia, asthenia, and troponin increased. Each term is accompanied by a reported frequency of 16.7%. The registry record does not identify a treatment group for each term, so those frequencies should not be assigned to a particular arm. The terms are event labels, not comparative estimates.

These figures describe participants affected, not necessarily the total number of distinct event episodes. Serious adverse events are not equivalent to all adverse events, and neither category alone establishes that the study treatment caused the event. General explanation: safety comparisons are harder to interpret when groups are small because a limited number of participants can account for a substantial share of the observed experience. The registry record provides no inferential safety comparison or uncertainty interval, so the reported figures do not establish the precision of differences between groups.

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

The posted results answer a narrow descriptive question: how many participants in each listed group had at least one TEAE by Week 24. The counts are 6 for IFX-1 high dose, 7 for IFX-1 low dose, and 5 for placebo. Serious adverse events are reported for 2, 1, and 0 participants, respectively, and no deaths are listed. These data describe what is recorded for the groups; they do not, on their own, establish a causal relationship between an intervention and an adverse event.

The record does not include an inferential comparison, confidence interval, or p-value for the primary endpoint. Consequently, it does not quantify how precisely the groups differ or how compatible the observed results are with no difference. The arm counts should not be treated as proof that the regimens have equivalent safety, nor as proof that one regimen has a higher or lower risk. Such claims would require an analysis and appropriate uncertainty estimates that are not reported.

The record also does not post analyses for its secondary clinical and laboratory outcomes. The listed outcomes identify what was measured, but their names are not results. No conclusion about clinical response, remission, or pharmacologic activity can be drawn from the list alone.

General explanation: a trial’s randomized and masked design can support a fairer treatment comparison when implemented as intended, but those design features do not eliminate uncertainty, especially when the available group counts are limited. The record does not provide enough information to assess the success of masking, the handling of missing data, or the analysis population rules. The study is marked terminated, but the reason for termination is not reported in the registry record. The most defensible reading is therefore that the registry records a small set of descriptive safety counts, while leaving comparative precision and broader outcome interpretation unresolved.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between recording outcomes and evaluating a treatment contrast. It has a randomized, triple-masked, parallel-group structure and a clearly stated participant-level safety endpoint. Those design features define the intended comparison among two IFX-1 regimens added to standard care and placebo added to standard care. Yet the posted primary results are counts without inferential analysis, so the structure of a comparison does not itself provide an estimate of its precision.

The small group counts make transparent reporting of uncertainty particularly important. Counts can summarize what happened in each group, but they cannot show how stable a difference might be across other samples. A confidence interval and a clearly described analysis would help readers assess the range of uncertainty; neither is reported in the registry record. The outcome’s stated percentage component also underscores the value of presenting denominators and methods alongside counts.

The record also illustrates why a list of outcomes is not equivalent to evidence about those outcomes. Clinical response, remission, and laboratory measures are named, but no analyses are posted. With several outcomes, a documented analysis plan and clear handling of multiplicity would help distinguish primary questions from exploratory ones. Those details are not reported in the registry record.

Finally, the record identifies a Safety Analysis Set but does not explain its membership or missing-data handling. Such information is relevant to the meaning of any observed proportion. The trial therefore offers a useful statistical lesson: design labels and endpoint definitions establish the framework, while transparent analysis methods, denominators, and uncertainty estimates are needed to interpret comparisons. The available record supports a careful description of safety counts, not a precise comparative conclusion.

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 outcome results are presented as counts, although the endpoint description includes both numbers and percentages. No per-group percentage values or inferential comparisons are posted. The record gives no confidence intervals or p-values, preventing an assessment of the precision of treatment contrasts.

The group sizes listed for the primary outcome are 6, 7, and 6, while the registry enrollment field is 20. The registry record does not explain the relationship between these figures. It also does not report participant flow, the number with missing Week 24 outcomes, or how missing observations were handled. The membership rules for the Safety Analysis Set are not given.

The study is marked terminated, but the reason is not reported in the registry record. Randomization details, the allocation ratio, actual dose levels, treatment schedules, and the roles covered by triple masking are not reported. The record also does not provide an original sample-size justification, a statistical analysis plan, interim analysis information, or a multiplicity strategy.

Seven secondary outcomes are listed, but analyses are not posted for them. The serious adverse-event terms are reported with frequencies but are not mapped to treatment groups. The posted summaries do not give event timing, duration, severity beyond the serious category, or participant-level detail. These limitations leave the results as a restricted descriptive account of selected safety outcomes rather than a complete evaluation of comparative safety or secondary outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA — NCT03712345.
• Registry record last updated 2022-05-26; status last verified 2022-05.
• Results first posted 2022-05-26.
• 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 randomized, triple-masked, parallel-group Phase II study of IFX-1 added to standard care for GPA and MPA, with placebo as the comparator. The study is marked terminated. Enrollment is listed as 20, with a recorded start date of 2018-10-15 and primary completion date of 2020-09-10.

The primary outcome is the number and percentage of participants with at least one TEAE by Week 24 in the Safety Analysis Set. Posted counts are 6 for IFX-1 high dose, 7 for IFX-1 low dose, and 5 for placebo. Serious adverse events are listed for 2, 1, and 0 participants, respectively; no deaths are recorded in the listed groups.

No inferential analyses are posted. The record does not report the reason for termination, original sample-size justification, missing-data handling, or the statistical plan. Secondary clinical and laboratory outcomes are listed without posted analyses.