A Study to Evaluate the Safety and Efficacy of AVTX-002 for the Treatment of Poorly Controlled Non-Eosinophilic Asthma.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Efficacy of AVTX-002 for the Treatment of Poorly Controlled Non-Eosinophilic Asthma. (NCT05288504), a randomized phase 2 study. The primary outcome is The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events..

2. Clinical Question

The primary objective was to evaluate the efficacy of AVTX-002 compared with placebo in patients with poorly controlled non-eosinophilic asthma. The registry describes the main outcome as the percentage of participants who experienced any qualifying asthma-related event through Week 14. These events include increased reliever use, a substantial increase in inhaled corticosteroid dose, a sustained decrease in peak flow, an exacerbation requiring systemic corticosteroids, or an exacerbation leading to hospitalization or an emergency room visit.

The result therefore addresses a combined question about whether participants experienced at least one event from a clinically varied list. It does not separately answer how often each type of event occurred, how severe each event was, or whether a particular component accounted for the observed group counts. Those component-specific results are not reported in the registry record. The comparison is between randomized groups; it is not a comparison of each group with its own baseline alone.

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study of AVTX-002 in poorly controlled non-eosinophilic asthma. The registry lists enrollment of 91 participants and status as completed. The study began on 2022-02-24, and primary completion was recorded as 2023-05-11. The registry describes approximately 40 participants planned for each arm, while the primary outcome results use 45 participants in each group. The registry record does not explain that difference between the approximate arm descriptions and the posted outcome denominators.

Participants were assigned to AVTX-002 or placebo. The AVTX-002 arm description states a dose of 600 mg three times during the study. The placebo was normal saline, also described as given three times. Randomization helps make treatment groups comparable on average, while double masking is intended to limit the influence of knowledge of assignment on participant behavior, care, and outcome assessment. The registry does not report further operational details about how allocation or masking was implemented.

The parallel-group structure means each participant was assigned to one study arm rather than crossing between the treatments. The principal comparison concerns the proportion of participants with any qualifying asthma-related event through Week 14. The primary outcome specifies the Full Analysis Set, but the criteria used to define that population are not reported in the registry record. The registry lists 13 outcome measures, including the primary outcome and secondary outcomes such as lung function, asthma control, symptoms, and quality of life. A detailed analysis result is posted for three secondary outcomes. The registry record does not report the trial's original sample-size justification, detailed statistical analysis plan, or interim-analysis plan.

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

Analysis population for the primary outcome, as defined in the registry: Full 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: Randomized Analysis Set

6. Primary Endpoint

The registry lists the primary outcome as The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events., measured over Through Week 14.

The primary endpoint counts participants who experienced any of several specified asthma-related events through Week 14. The listed events include at least 6 additional short-acting beta-agonist reliever puffs compared with baseline in a 24-hour period on 2 consecutive days; an increase in inhaled corticosteroid dose at least 4 times the baseline dose; a decrease in peak flow of 30% or more compared with baseline on 2 consecutive days; an asthma exacerbation requiring systemic corticosteroids for at least 3 days; or an exacerbation leading to hospitalization or an emergency room visit.

The endpoint is a composite: a participant is counted if any qualifying event occurs. Such an endpoint can capture several ways in which asthma control may worsen and can be more informative than looking only at one event type. However, the components differ in nature and severity. A single combined count cannot show which component occurred, how many times it occurred, or whether the groups differed on any one component. Those component-level counts are not reported in the registry record.

The registry reports 12 participants with an event among 45 in the AVTX-002 group and 14 among 45 in the placebo group. The corresponding posted risk estimates are 0.267 and 0.311. This endpoint is used to compare the groups on the occurrence of at least one event, not to establish a mechanism or to describe every aspect of asthma control.

7. Results Posted in the Registry

• AVTX-002: 26.7% (12/45) versus 31.1% (14/45) on control; risk difference -4.4 percentage points (95% CI -23.1 to 14.3), risk ratio 0.86 (0.45–1.64); unadjusted two-proportion z-test p = 0.642.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]).

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AVTX-002: mean -0.15 versus -0.20 on control; difference 0.05 (95% CI -0.10 to 0.21), standardized effect d = 0.15; z-test p = 0.492.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AVTX-002 and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO).

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AVTX-002: mean 6.10 versus 3.80 on control; difference 2.30 (95% CI -7.29 to 11.89), standardized effect d = 0.10; z-test p = 0.638.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AVTX-002 and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ).

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AVTX-002: mean -0.22 versus -0.34 on control; difference 0.12 (95% CI -0.32 to 0.56), standardized effect d = 0.12; z-test p = 0.597.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AVTX-002 and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes span several kinds of measurement: lung function, airway inflammation, asthma control, exacerbation timing, symptom burden, quality of life, and patient-reported impressions. The registry lists these as additional outcomes alongside the primary composite event endpoint. Detailed results are posted for FEV1, FeNO, and ACQ; full numerical results for the other listed secondary outcomes are not reported in the registry record.

The available detailed estimates do not establish a clear, precise separation between AVTX-002 and placebo. The mean-difference intervals for the three outcomes include zero, and their unadjusted p-values are 0.492, 0.638, and 0.597, respectively. This overall pattern is consistent with uncertainty in the secondary comparisons rather than a decisive, uniform signal across the available measures. It does not demonstrate that all outcomes were identical or that every unreported outcome followed the same pattern.

Secondary outcomes can help describe whether the primary result aligns with other domains, but they have a different evidentiary role. The primary endpoint is the stated principal comparison; secondary outcomes often address supporting or exploratory questions. When multiple outcomes are examined, the chance of observing an apparently notable result by chance can increase. The registry labels the posted p-values unadjusted and does not report a multiplicity procedure. Consequently, isolated secondary findings would need cautious interpretation and should not be treated as independent confirmation without considering the full analysis plan and outcome family.

The registry reports 12 secondary outcomes, while detailed numerical comparisons are available for three. The reasons for which results are or are not posted are not reported in the registry record. The breadth of registered outcomes should therefore be kept distinct from the narrower set of outcomes with detailed statistics. Taken together, the available secondary summaries provide context for the primary comparison, but they do not overcome the primary estimate's uncertainty or answer questions about the unreported outcome results.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]).
• Time to Asthma Exacerbation.
• Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO).
• Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ).
• Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12).
• Change From Baseline to Week 14 in Asthma Symptom Diary Score.
• Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS).
• Change From Baseline to Week 14 in Patient Global Impression of Change/Severity.

9. Statistical Interpretation

10. Statistical Methods Explained

The trial is listed as randomized, double-blind, and parallel group. Randomization is a design method intended to balance measured and unmeasured characteristics between groups on average. Double masking reduces the opportunity for expectations about assigned treatment to influence behavior or assessment. These design features support a comparative interpretation, but they do not remove uncertainty from a small set of observed outcomes or substitute for a fully described analysis plan. The registry record does not report the allocation procedure, concealment details, or how masking was maintained.

What does the primary estimate represent?

The primary comparison is a risk difference: the event risk in the AVTX-002 group minus the event risk in the placebo group. The posted estimate is -0.044. A negative value indicates that the observed risk was lower in the AVTX-002 group; it does not by itself establish that the groups differ beyond sampling uncertainty. The registry also posts risk and odds ratio summaries, but the risk difference is the measure emphasized for interpreting the absolute separation between the two group risks.

The underlying outcome is binary at the participant level: each participant is classified according to whether at least one listed event occurred. The posted counts are 12 of 45 and 14 of 45. A binary summary is straightforward to interpret, but it compresses multiple events and event types into a single indicator. It does not retain how many qualifying events occurred per person or distinguish the components of the composite.

How should the confidence interval and p-value be read?

In general, a confidence interval describes the range of values reasonably compatible with the observed data and the statistical method used. The 95% confidence interval for the primary risk difference extends from -0.232 to 0.143. Because it spans values on either side of no difference, the data do not pin down the direction of the underlying group contrast with high precision. The interval does not assign a probability to the true difference, and its interpretation depends on the assumptions of the method used to construct it.

The unadjusted p-value is 0.642. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that null hypothesis and the test assumptions were true. It is not the probability that the treatment has no effect, and it is not a measure of clinical importance. The registry does not report the specific test, model, covariate adjustment, or confidence-interval procedure for the primary comparison. As a result, the posted summary can be described, but details of the inferential method cannot be independently reconstructed from the registry record.

What is meant by an unadjusted result?

An unadjusted result is presented without an adjustment for other variables or for the multiplicity created by testing multiple outcomes, unless otherwise specified. The record labels the reported p-values as unadjusted. That does not mean the randomized groups were not randomized; it concerns the analysis presentation. The registry record does not report whether additional covariate-adjusted analyses were conducted or whether the primary analysis used a different procedure.

When many outcomes are examined, some results can appear notable by chance even when there is no underlying difference. Multiplicity methods can control how that chance accumulates across a defined family of tests. The registry does not report a multiplicity strategy. Therefore the secondary p-values, where posted, should not be treated as if each were the sole prespecified test.

Why do secondary outcome summaries use different measures?

The available detailed secondary measures are continuous changes from baseline to Week 14. For FEV1, FeNO, and ACQ, the registry reports group means, standard deviations, mean differences, confidence intervals, and unadjusted p-values. A mean difference compares the average change between groups, using AVTX-002 minus placebo. For these continuous outcomes, the posted mean differences are 0.054 liters for FEV1, 2.3 parts per billion for FeNO, and 0.12 score units for ACQ. Their intervals extend from -0.100 to 0.208, -7.29 to 11.89, and -0.324 to 0.564, respectively.

In general, a standard deviation describes variation among participant measurements, while a confidence interval for a mean difference describes uncertainty in the group contrast. These are not interchangeable: a standard deviation characterizes dispersion in observations, whereas the interval concerns uncertainty in the estimated difference. The registry lists 42 participants per arm for these secondary summaries. The reasons why these denominators differ from the primary outcome denominators are not reported in the registry record.

What can and cannot be inferred from planning illustrations?

The planning illustrations use the observed effect as a starting point and show hypothetical participant requirements for specified fractions of that effect. They are not the trial's original design justification. In general, power is the probability that a study will detect an effect of a specified size under chosen assumptions if that effect is real. A planning estimate depends on assumptions about the effect, variability or event rate, allocation, significance level, and analysis method. The registry record's listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The targeted effect is the stated fraction of the observed effect.

The registry does not report the original sample-size assumptions or justification, so the planning illustrations should not be read as the rationale for enrolling the trial participants. Nor do they establish the probability that this completed trial detected an effect. They are prospective-style calculations using the observed summaries, and are useful only as conditional illustrations. The original analysis plan, any interim analyses, and detailed missing-data procedures are not reported in the registry record.

11. Confidence Intervals and Precision

The primary estimate is a risk difference of -0.044, with a 95% confidence interval from -0.232 to 0.143. This range is wide enough to include a meaningful decrease as well as an increase in the event risk for AVTX-002 relative to placebo. The point estimate alone therefore gives an incomplete account: the confidence interval communicates that the data do not precisely determine the direction or size of the contrast.

In general, confidence intervals reflect both the amount of information in the data and the statistical assumptions used in their construction. The primary comparison is based on 45 participants in each group. With a binary composite outcome, the amount of information also depends on how many participants experience events. The registry record does not provide individual observations, details of missing outcomes, or the method used to calculate the interval, so precision cannot be assessed beyond the posted interval and denominators.

The secondary estimates are also uncertain. The FEV1 mean difference is 0.054 liters, with an interval from -0.100 to 0.208; the FeNO mean difference is 2.3 parts per billion, with an interval from -7.29 to 11.89; and the ACQ mean difference is 0.12 score units, with an interval from -0.324 to 0.564. Each interval includes zero, while the widths indicate that a range of group contrasts remains compatible with the data. These intervals are not evidence that the underlying effects are exactly zero. They indicate that the posted estimates do not sharply resolve the differences.

Precision should be distinguished from importance. A narrow interval can estimate an effect precisely without showing whether it matters to patients, and a wide interval can leave important possibilities unresolved. The registry record does not report thresholds for clinically important differences for these outcomes. Interpretation should therefore stay with the estimated contrasts, their uncertainty, and the limits of the available summaries.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for each of the listed binary and continuous outcomes; they are not total event counts. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculation targets the stated fraction of the observed effect. The trial's own original design assumptions and sample-size justification are not reported in the registry record.

For each assumed effect size, the 80% power column gives the illustrative number of participants per arm that would yield an 80% chance of detecting an effect of that size under the stated assumptions, if the assumed effect were the true effect. The 90% power column describes the corresponding planning target for a 90% chance. In general, a higher power target requires more participants, all else equal. The figures are planning illustrations, not observed power.

Rows using 100% of the observed effect use the observed estimate as the target. Rows using 75% or 50% of the observed effect target smaller differences. Smaller effects are harder to distinguish from random variation and require more participants, which is reflected by larger planning requirements in those rows. The illustration depends strongly on the observed estimate. In particular, an imprecise estimate from a small trial may not be a stable basis for planning a future study.

The displayed planning figures should not be interpreted as a recommendation for a future trial or as evidence about the adequacy of this trial's original enrollment. They do not incorporate assumptions that are not listed, such as a specific missing-data allowance or an analysis strategy not described in the registry record. The registry record does not report whether the trial's original planning used the same significance level, allocation assumptions, or effect target.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.311; treatment proportion p₁ = 0.267; average p̄ = 0.289.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6410 = 1.2563.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6402 = 0.5388.
4. n = (1.2563 + 0.5388)² / (-0.0444)² = 1,631.4, rounded up to 1,632 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.311111111111111                          # control proportion
p1 <- 0.266666666666667                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5288504)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,632 (80% power), 2,184 (90% power)
 75% of observed effect: n per arm = 2,934 (80% power), 3,928 (90% power)
 50% of observed effect: n per arm = 6,675 (80% power), 8,935 (90% power)
power.prop.test: 1631.4 
Simulated power at n = 1,632 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and 12 secondary outcomes. It reports detailed results for the primary outcome and three secondary outcomes, with unadjusted p-values for the available comparisons. Testing multiple outcomes creates a multiplicity concern: even if none of the underlying effects differs from zero, a collection of tests can produce apparently unusual results by chance. A prespecified strategy can address that concern by defining which tests are confirmatory and how error rates are controlled.

The registry record does not report whether such a strategy was used, how outcomes were prioritized beyond the designated primary outcome, or whether secondary tests were adjusted. The posted secondary p-values should therefore be read as unadjusted summaries and not as a family-wise conclusion. The record also does not report whether subgroup analyses or additional exploratory analyses were conducted.

Missing-data handling is another important element of a clinical-trial analysis. The primary outcome is reported for the Full Analysis Set, but the registry record does not give the set's detailed inclusion rules, the number of missing primary outcomes, the reasons for missingness, or the method used to handle missing observations. For the three detailed continuous secondary outcomes, 42 participants per arm are listed, but the registry does not explain the denominators or indicate how missing measurements were handled. These differences in available denominators cannot be attributed to a specific cause from the registry summaries alone.

The registry record also does not report the primary statistical model, covariates, sensitivity analyses, or whether analyses followed an intention-to-treat principle. The named Full Analysis Set should not be assumed to have any particular definition beyond its label. No interim-analysis plan is reported. Without these details, the posted estimates can be described, but the robustness of the results to analysis choices, missing data, and multiple testing cannot be fully evaluated.

15. 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 non-serious adverse event terms

The registry reports zero serious adverse events among 45 participants at risk in the AVTX-002 group and zero among 45 participants at risk in the placebo group. It also reports zero deaths in each group. These counts describe the serious-event and death summaries recorded for the trial; they do not establish that no adverse events of any kind occurred.

For other, non-serious adverse events, the registry reports 19 affected participants among 45 at risk in the AVTX-002 group and 21 among 45 at risk in the placebo group. These are participant counts, not counts of every event occurrence. The record does not provide the specific non-serious event terms in the information, nor does it report exposure-adjusted rates or detail about event severity, timing, or relatedness.

Safety figures should be interpreted with the study's size and follow-up in mind. A zero count for a serious outcome means no such event was recorded in the listed group during the reported observation; it does not rule out the possibility of uncommon events. The registry summaries alone do not support a broad conclusion about comparative safety beyond these recorded counts.

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

The posted primary result is a comparison of participants who experienced at least one of several asthma-related events through Week 14. The observed counts were 12 of 45 with AVTX-002 and 14 of 45 with placebo. The estimated risk difference favors a lower observed event risk in the AVTX-002 group, but the 95% confidence interval includes values in both directions. The result therefore describes a difference in the observed sample without precisely establishing the underlying group contrast.

It does not show that the groups are equivalent. Failure to obtain a small p-value is not a formal equivalence finding; equivalence requires a predefined margin and an analysis designed to assess it, neither of which is reported in the registry record. It also does not show that the observed point estimate is the true effect. Sampling uncertainty remains substantial, and the record does not include enough analysis detail to assess all modeling and missing-data assumptions.

The endpoint combines distinct types of events. The overall participant count cannot say which component drove the result, whether components differed in importance, or whether participants experienced repeated events. Component-specific counts and repeated-event summaries are not reported in the registry record. Nor do the detailed secondary summaries provide a complete account of all registered outcomes: numerical results for several listed outcomes are not reported in the registry record.

The study is a Phase 2 trial in a defined population of poorly controlled non-eosinophilic asthma. Results from this trial alone do not establish what would occur in other populations, with other treatment regimens, or over other follow-up periods. The registry record also does not report a basis for generalizing the findings beyond the enrolled participants. The findings are best read as estimates from a randomized comparison with meaningful uncertainty, rather than as a final answer about all clinical or scientific questions concerning AVTX-002.

17. Why This Trial Matters Statistically

This trial illustrates how a randomized design and a clear primary outcome can still yield an uncertain estimate. The primary comparison gives an absolute risk difference and a confidence interval, allowing readers to see both the direction of the observed contrast and the range of values compatible with the data. The interval is essential: the point estimate alone would obscure how much uncertainty remains.

The composite endpoint also highlights a common statistical trade-off. Combining multiple event types can capture a broader picture of worsening asthma control, but it can conceal differences among components. A participant-level composite count is not a substitute for component-specific reporting. Readers need to know both what qualifies as an event and whether the total result reflects similar patterns across components.

The registry record offers a useful example of why analysis transparency matters. Detailed secondary results are available for only part of the registered outcome set, and the record does not report multiplicity control, missing-data procedures, the statistical model, or the original sample-size justification. Those gaps do not invalidate the posted numbers, but they limit how fully their reliability and context can be assessed.

Finally, sample-size illustrations based on observed effects show how planning requirements depend on the effect one hopes to detect. They are not a retrospective score of whether the completed trial had adequate power. Distinguishing planned design assumptions from post hoc planning illustrations helps prevent overstating what a trial's size can tell readers. Together, these statistical considerations support a cautious reading of the results and a clear separation between observed summaries, uncertainty, and questions the registry does not answer.

18. 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 comparison has limited precision, as reflected by the 95% confidence interval from -0.232 to 0.143. The interval includes a range of possible differences, so the point estimate should not be treated as a precise measure of the group contrast. The registry lists 91 participants enrolled, while the primary endpoint summaries list 45 participants per group; it does not explain the difference or report details on missing outcomes and exclusions.

The primary outcome is a composite of multiple event types with different definitions and potential severity. Although the registry describes the components, it does not report their separate counts. A single overall result therefore cannot identify which type of event contributed to the group comparison. The registry also does not report how event adjudication was conducted or whether adjudicators remained masked.

Only three secondary outcomes have detailed numerical comparisons in the record, even though 12 secondary outcomes are listed. The record does not report results for the remaining registered secondary outcomes, multiplicity handling, or whether any additional analyses were performed. Unadjusted secondary results are consequently limited as evidence across a broad outcome set.

Further limitations concern analysis transparency. The registry record does not report the primary test or model, covariate adjustment, missing-data methods, sensitivity analyses, the Full Analysis Set definition, interim analyses, or the original sample-size justification. It also does not give component-level safety details in the summaries. These omissions restrict independent assessment of robustness and the extent to which the posted comparisons answer the original trial questions.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Efficacy of AVTX-002 for the Treatment of Poorly Controlled Non-Eosinophilic Asthma. — NCT05288504.
• Registry record last updated 2024-09-05; status last verified 2024-08.
• Results first posted 2024-09-05.
• 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.

22. Record Summary

NCT05288504 is a completed randomized, double-blind, placebo-controlled, parallel-group Phase 2 study of AVTX-002 for poorly controlled non-eosinophilic asthma. Enrollment was 91. The recorded start date was 2022-02-24, and primary completion was 2023-05-11.

Through Week 14, the primary composite asthma-event outcome was reported for 45 participants per group: 12 in the AVTX-002 group and 14 in the placebo group. The risk difference was -0.044, with a 95% confidence interval from -0.232 to 0.143 and an unadjusted p-value of 0.642. Detailed secondary comparisons are posted for FEV1, FeNO, and ACQ; each reported interval includes zero.

The registry reports zero serious adverse events and zero deaths in each group, alongside 19 participants with other adverse events in the AVTX-002 group and 21 in the placebo group. Important analysis details, including missing-data procedures, multiplicity handling, and the trial's original sample-size justification, are not reported in the registry record.