Study to Evaluate the Safety, Phage Kinetics, and Efficacy of Inhaled AP-PA02 in Subjects With Non-Cystic Fibrosis Bronchiectasis and Chronic Pulmonary Pseudomonas Aeruginosa Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, Phage Kinetics, and Efficacy of Inhaled AP-PA02 in Subjects With Non-Cystic Fibrosis Bronchiectasis and Chronic Pulmonary Pseudomonas Aeruginosa Infection (NCT05616221), a randomized phase 2 study. The primary outcome is P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation.

2. Clinical Question

3. Trial Design

This was a Phase 2, multi-center, randomized, parallel-group, placebo-controlled study sponsored by Armata Pharmaceuticals, Inc. The registry record lists triple masking, while the official title describes the study as double-blind. It reports enrollment of 48 and a completed status. The recorded start date is 2023-01-10, and the primary completion date is 2024-07-17.

The study evaluated inhaled AP-PA02, described as an anti-pseudomonal bacteriophage, against placebo, an inactive isotonic solution. The reported arms are organized into Cohort A and Cohort B, with each cohort listing lower-dose AP-PA02, higher-dose AP-PA02, and placebo. The posted primary outcome summaries contain results for the higher-dose and placebo groups in each cohort. No primary outcome values are posted for the lower-dose groups, whose listed outcome group sizes are 0.0.

The primary analysis population description adds important context. According to the Statistical Analysis Plan, participants enrolled before the first DSMB meeting who received the lower dose were not included in the primary analysis. It also reports that two participants were excluded due to major protocol deviations. The remaining reason text is incomplete in the registry record. The outcome summaries therefore should not be read as a simple account of every randomized participant.

The study assessed safety, phage kinetics, and efficacy, but the registry record does not report the full protocol or the original statistical design details. The number of planned enrollment is not separately described; the record reports enrollment of 48. The original sample-size justification, allocation ratio, and intended statistical analysis plan beyond the population description 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: According to the Statistical Analysis Plan, participants who enrolled before the first DSMB meeting received a lower dose of AP-PA02 (1.5×10¹¹ PFU) and were not included in the primary analysis. In addition, two participants were excluded due to major protocol deviations related to study drug compliance. After applying these prespecified criteria, 41 participants were included in the primary outcome analysis.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation, measured over Day 17.

The primary endpoint measures change from baseline in P. aeruginosa density in induced sputum. Density is expressed in colony forming units log10, and the registry describes the reported statistic as a mean with standard deviation. The measurement is specified for Day 17, one week after the end of treatment. A change score expresses how the measured value at follow-up differs from the participant’s baseline value; a negative group mean indicates a decrease in the measured density on the reported scale.

Sputum sampling provides a measure of the bacteria recovered from the respiratory specimen. The endpoint therefore focuses on a laboratory measure rather than a direct measure of symptoms, daily functioning, or another clinical outcome. It is relevant to a study evaluating an anti-pseudomonal phage therapeutic because it tracks the organism named in the study population and intervention rationale. That relevance does not make the sputum result a complete description of clinical benefit or harm.

The posted primary outcome is reported by cohort and treatment group. The formal comparison posted in the registry is for Cohort A: AP-PA02 at 3x10^11 PFU/Dose versus placebo. No confidence limits are given for the individual group means. Interpretation of the group contrast therefore relies on the posted comparison interval and its uncertainty, as well as on the limits of the recorded analysis population.

7. Results Posted in the Registry

• Cohort A: AP-PA02, 3x10^11 PFU/Dose: mean -0.50 versus -0.10 on control; difference -0.40 (95% CI -1.11 to 0.31), standardized effect d = -0.45; z-test p = 0.270.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome and summarizes each group using a mean and standard deviation. A mean describes the average observed change in the group. The standard deviation describes how dispersed individual values are around that average; a larger standard deviation means the observations vary more. For Cohort A, the posted mean changes are -0.5 for AP-PA02 and -0.1 for placebo, while their standard deviations are 0.72 and 1.11. These statistics summarize different features: the means describe the group-level changes, and the standard deviations describe the spread of participant-level changes.

What does the mean difference express?

The registry’s comparison reports a mean difference of -0.4 for Cohort A AP-PA02 versus placebo. It is the estimated difference between the reported group means, with the direction depending on which group is subtracted from the other. Here, the listed group means make the direction clear: -0.5 for AP-PA02 and -0.1 for placebo. A negative contrast therefore corresponds to a more negative average change in the AP-PA02 group. This arithmetic contrast is an estimate, not a declaration that the intervention caused the difference.

The comparison also lists a pooled standard deviation and a standardized effect-size statistic. These are ways to express the observed contrast in relation to variation in the outcome. They can aid comparisons across scales, but they do not remove uncertainty, confounding, or limits of the analysis population. The posted standardized statistic is -0.448; it should be understood as a standardized description of the observed contrast, rather than as a separate clinical outcome.

How should the p-value be understood?

The registry reports an unadjusted p-value of 0.27. In general, a p-value describes how compatible the observed data are with a specified null model, assuming that model and the analysis conditions hold. It is not the probability that the null model is true, the probability that the result arose by chance, or a measure of the size or importance of an effect. A value above a conventional threshold does not prove that there is no difference. The record does not state a significance threshold for the trial’s own primary analysis, so no claim about the original decision rule can be made.

“Unadjusted” means the reported p-value is not presented as corrected for multiple testing. The record does not report a multiplicity strategy. If several outcomes, comparisons, or analysis choices are examined, the chance of at least one apparently notable result can increase; adjustment methods are designed to address that issue. This is a general statistical consideration, not a statement that a particular adjustment was required or used in this study.

What does the confidence interval add?

A confidence interval expresses uncertainty around an estimated effect under the statistical method used. It gives a range of values compatible with the data and method at the stated confidence level. The registry comparison interval extends from -1.111 to 0.311. Because it spans zero, it includes no mean difference as well as negative and positive differences. Its breadth indicates that the point estimate alone does not give a precise account of the underlying contrast. The confidence level and the interval calculation method are not reported in the record, so the exact procedure should not be assumed.

Why do sample size and variation matter?

For a continuous outcome, precision depends in part on the size of the groups and the variability of measurements. Smaller groups and more dispersed observations generally make an estimate less precise. In Cohort A, the outcome group sizes are 18 and 12, and the standard deviations differ between groups. In Cohort B, the placebo group size is 3 and the standard deviations are 1.63 and 1.13. These are descriptive summaries, and the record does not report a formal model for handling differences in variance or cohort structure.

Over-dispersion is a general concern when observed variability is larger than the model assumes. For continuous outcomes, an inappropriate assumption about spread can make standard errors and confidence intervals too optimistic or too wide. The posted group standard deviations give a view of observed variation, but the registry does not describe a diagnostic assessment or an adjustment for over-dispersion. It would be inappropriate to infer that such checks were or were not performed.

What is not specified about the analysis?

The registry record does not report the confidence level, the full model specification, handling of missing endpoint data, or a detailed account of covariate adjustment. It also does not report the intended analysis populations beyond the exclusion description. The posted comparison is an unadjusted summary contrast with an unadjusted p-value; more detailed claims about the sponsor’s modeling or analysis plan are not justified by the record. These limitations matter because results can depend on choices about analysis population, missing values, adjustment, and how multiple outcomes are handled.

10. Confidence Intervals and Precision

The Cohort A mean difference is -0.4, with a reported confidence interval from -1.111 to 0.311. The interval includes zero, meaning that no mean difference lies within the range of values compatible with the posted estimate and interval procedure. It also includes negative and positive values. The direction of the point estimate favors a larger mean decrease in the AP-PA02 group, but the interval indicates uncertainty about the direction and magnitude of the underlying contrast.

The interval is wide relative to the point estimate. Its lower endpoint permits a larger negative difference than the estimate, while its positive endpoint permits a difference in the opposite direction. This is why the estimate should not be reduced to the point value alone. The unadjusted p-value of 0.27 is consistent with the interval’s inclusion of zero, although the record does not report the exact interval method or confidence level.

Precision is also limited by the sizes and variability of the outcome groups. The Cohort A comparison uses 18 participants in the AP-PA02 group and 12 in placebo, and the standard deviations are 0.72 and 1.11. The confidence interval reflects uncertainty in the contrast, not the range within which every participant’s change must fall. Participant-level changes may be more dispersed than the interval around the group mean difference suggests.

The registry reports no confidence limits for the individual group means, and it provides no formal comparison interval for Cohort B. The Cohort B means therefore remain descriptive. The record also does not report the confidence level, so the interval should be interpreted as posted without assuming an unstated level or method.

11. 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 sample-size figures are planning illustrations based on the observed Cohort A contrast, not the trial’s original design calculation. The listed counts are participants per arm, not a combined total and not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the number of participants per arm required, under those assumptions, for an 80% chance of detecting the chosen effect if that effect is the true one. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a property of a proposed design under assumed conditions; it is not the probability that the observed result is correct.

For planning for 100% of the observed effect, the illustration lists 79 participants per arm for 80% power and 105 per arm for 90% power. For planning for 75% of the observed effect, the corresponding figures are 140 and 187 participants per arm. For planning for 50% of the observed effect, they are 314 and 420 participants per arm. The pattern reflects a general statistical principle: smaller effects are harder to distinguish from random variation and require more participants under otherwise unchanged assumptions.

The curve is a visual companion to these planning values and should be read with the same assumptions and interpretation. These counts are not observed power, and they do not establish what the trial’s original sample-size target or design rationale was. The original design assumptions and sample-size justification are not reported in the registry record.

12. 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.400; pooled standard deviation σ = 0.894.
2. n = 2 × (1.96 + 0.842)² × 0.894² / -0.400² = 78.4, rounded up to 79 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
delta <- -0.4                      # observed difference in means
sigma <- 0.893746128862745                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5616221)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 79 (80% power), 105 (90% power)
 75% of observed effect: n per arm = 140 (80% power), 187 (90% power)
 50% of observed effect: n per arm = 314 (80% power), 420 (90% power)
power.t.test: 79.3 
Simulated power at n = 79 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record reports two outcome measures overall and no posted secondary outcome results. It lists zero separate analysis records, while still providing primary outcome group summaries and a comparison. The record does not describe a complete prespecified analysis plan, a hierarchy of outcomes, or a multiplicity adjustment. The reported p-value is explicitly unadjusted. It is therefore not possible to determine from the registry record whether the posted comparison was the only planned test, one of several planned tests, or selected from a broader set of analyses.

Multiplicity matters when several statistical tests are performed. As a general principle, testing multiple outcomes or treatment contrasts without adjustment can increase the chance of a false-positive finding. Different adjustment strategies may control that risk in different ways, but no strategy should be attributed to this study without documentation. The absence of a reported strategy is a reporting limitation; it does not establish that no strategy existed outside the registry record.

Missing-data handling is not reported in the registry record. The record does not state how participants without a Day 17 sputum measurement were treated, whether any values were imputed, or how missingness was assessed. Such decisions can affect the analysis population and the estimated group contrast. The reported outcome group sizes alone do not explain the flow from enrollment or randomization to the primary analysis.

The primary outcome population description does provide two exclusions: participants enrolled before the first DSMB meeting who received the lower dose were not included in the primary analysis, and two participants were excluded because of major protocol deviations. The remainder of the description is incomplete. The record does not identify the primary analysis as intention-to-treat, per-protocol, or another named population, and it does not explain all exclusions or deviations. Consequently, the reported contrast should be interpreted as applying to the registry’s reported analysis groups, rather than assumed to represent a particular standard analysis population.

14. 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: urinary tract infection (25.0%), bronchiectasis (22.2%), hypoxia (11.1%), infective exacerbation of bronchiectasis (5.3%).

The registry reports serious adverse events as the number of participants affected and the number at risk in each arm. In Cohort A, the serious-event counts were 1 of 4 for the lower-dose AP-PA02 group, 1 of 19 for the higher-dose group, and 0 of 12 for placebo. In Cohort B, the counts were 0 of 1 for lower-dose AP-PA02, 3 of 9 for higher-dose AP-PA02, and 0 of 3 for placebo. The registry reports zero deaths in every listed group.

These are descriptive safety counts, not a powered comparison of risks. The groups are small, and the number at risk differs across arms and cohorts. A count of affected participants is not necessarily the same as the count of all event episodes. The registry lists urinary tract infection, Bronchiectasis, Hypoxia, and Infective exacerbation of bronchiectasis among the top serious-event terms, with percentages of 25.0%, 22.2%, 11.1%, and 5.3%, respectively. The record does not explain the denominator for those term percentages, so they should not be treated as arm-specific rates.

Other adverse events are also reported, but these should be distinguished from serious adverse events. The serious-event figures alone do not provide a complete account of event severity, timing, relatedness, or clinical course.

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

The posted primary result is an estimate of the mean difference in change from baseline in sputum P. aeruginosa density at Day 17 for Cohort A AP-PA02 at 3x10^11 PFU/Dose compared with placebo. The point estimate is -0.4, with a confidence interval that includes zero and an unadjusted p-value of 0.27. The observed group means point toward a larger decrease in the AP-PA02 group, but the uncertainty interval allows for no difference and for a difference in the opposite direction. The result is therefore uncertain.

The result does not establish that AP-PA02 does or does not have an effect. A confidence interval containing zero is not proof of equivalence, and the p-value is not a probability that the treatment is ineffective. Conversely, a negative point estimate is not proof that the observed contrast is caused by the intervention. The sizes and variability of the analysis groups, incomplete reporting of analysis details, and absence of participant-level data limit what can be concluded from this registry record.

The endpoint measures a laboratory quantity in induced sputum, not symptoms, quality of life, lung function, or another clinical outcome. A change in sputum density should not be treated as interchangeable with a change in how a participant feels or functions. The registry describes the broader study aims as including safety, phage kinetics, and efficacy, but the posted primary comparison does not answer every question about those aims.

The Cohort B summaries are descriptive and have no posted formal contrast. They do not resolve the uncertainty in the Cohort A comparison. The registry also reports no secondary outcome results and does not provide a full analysis plan, missing-data approach, or complete description of the analysis population. These limits make it important to distinguish what the registry shows—the recorded group summaries and comparison—from broader claims about clinical effect or safety.

16. Why This Trial Matters Statistically

This trial raises several statistical issues that are common in early clinical studies. The primary endpoint is a continuous change score, so the group means provide a concise contrast, while the standard deviations show that individual observations vary around those means. Reading the estimate alongside its confidence interval prevents the point estimate from being mistaken for a precise or definitive result. In this study, the interval includes zero and extends in both directions.

The analysis population also matters. The registry says that lower-dose participants enrolled before the first DSMB meeting were not included in the primary analysis and that two participants were excluded for major protocol deviations. Those exclusions distinguish the primary analysis summaries from a simple all-enrolled comparison. Without a complete participant flow or named analysis population, readers cannot fully assess how the reported groups relate to the randomized study population.

Separating cohorts and dose groups is important as well. Cohort A has a posted formal comparison, whereas Cohort B has descriptive group means and no reported comparison. Treating those summaries as one pooled result would require an analysis that is not reported. Likewise, the absence of posted secondary outcomes and a multiplicity plan limits interpretation of the unadjusted p-value.

Finally, planning illustrations based on an observed effect can help readers understand how assumptions about effect size and power influence proposed group sizes. They do not reveal the trial’s original design rationale, and they are not a substitute for interpreting the actual estimate and its uncertainty. The registry supports a careful statistical reading of a small, cohort-specific comparison; it does not support broad conclusions beyond the recorded endpoint and analysis.

17. 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 registry record leaves several trial-specific details unavailable. It does not report the complete protocol, the original sample-size justification, the planned significance threshold, the confidence level used for the interval, or the full statistical model. The planning illustration uses its own stated assumptions and should not be mistaken for the trial’s design calculation.

The primary analysis population description is incomplete at its final phrase. It identifies the exclusion of lower-dose participants enrolled before the first DSMB meeting and two participants excluded because of major protocol deviations, but it does not give a complete account of participant flow or all reasons for exclusion. The record does not specify whether the analysis was intention-to-treat, per-protocol, or another defined population.

Missing endpoint data handling is not reported. The registry does not explain how absent sputum measurements were treated, whether analyses were adjusted for baseline values or other factors, or how the cohort structure was incorporated. The primary comparison is limited to Cohort A at the higher dose versus placebo; Cohort B has small descriptive groups and no posted formal comparison. No lower-dose primary outcome values are posted.

The registry reports no secondary outcome results and no multiplicity strategy. It also does not provide confidence intervals for individual group means, a formal Cohort B contrast, or participant-level data. These limitations restrict independent assessment of model assumptions, robustness, subgroup patterns, and the relationship between the reported analysis groups and all enrolled participants.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, Phage Kinetics, and Efficacy of Inhaled AP-PA02 in Subjects With Non-Cystic Fibrosis Bronchiectasis and Chronic Pulmonary Pseudomonas Aeruginosa Infection — NCT05616221.
• Registry record last updated 2026-01-05; status last verified 2025-11.
• Results first posted 2026-01-05.
• 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.

21. Record Summary

The record describes a completed Phase 2, multi-center, randomized, parallel-group, placebo-controlled study of inhaled AP-PA02 in subjects with non-cystic fibrosis bronchiectasis and chronic pulmonary Pseudomonas aeruginosa infection. It reports enrollment of 48, triple masking, and a primary outcome measuring change from baseline in sputum P. aeruginosa density at Day 17.

The posted formal primary comparison is for Cohort A AP-PA02 at 3x10^11 PFU/Dose versus placebo. The mean difference is -0.4, with a confidence interval that includes zero and an unadjusted p-value of 0.27. Cohort B results are descriptive. The registry also reports serious adverse-event counts and zero deaths in each listed group.

The record does not report the original sample-size justification, full analysis plan, missing-data method, or a multiplicity strategy. The posted result should be read as an uncertain, cohort-specific estimate of a sputum-measure difference, with limitations in the reported analysis details.