Phase 2a Evaluation of PLN-74809 on αvβ6 Receptor Occupancy Using PET Imaging in Participants With IPF/: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2a Evaluation of PLN-74809 on αvβ6 Receptor Occupancy Using PET Imaging in Participants With IPF/ (NCT04072315), a non-randomized phase 2 study. The primary outcome is Number of Participants With a Predicted Effect on αVβ6 PET ( Positron Emission Tomography) in Lungs After Administration of Drug..

2. Clinical Question

3. Trial Design

This completed phase 2a study evaluated PLN-74809 in participants with idiopathic pulmonary fibrosis using αVβ6 PET imaging. The registry record lists an enrollment of 9 and describes the study as non-randomized, unmasked, and crossover. Its recorded start date is 2020-02-13, and its primary completion date is 2022-06-27.

The listed dose levels are 60 mg, 80 mg, 120 mg, 240 mg, and 320 mg. The arm descriptions include single-dose-level groups as well as groups receiving combinations of dose levels, such as 80 mg and 240 mg. This crossover structure means that some listed group labels refer to more than one dose. The record does not give enough detail to reconstruct the order, timing, or conditions of each exposure, so those features should not be inferred.

The primary endpoint concerns predicted effects on lung αVβ6 PET after administration of study drug, with the timeframe stated as following one day of dosing. The registry describes measurement of PET tracer binding before and after drug administration and PK/PD modeling. It also lists safety and tolerability, measured by the number or percentage of adverse events, as a secondary outcome.

Because allocation was non-randomized, the listed dose groups are not a randomized comparison and should not be treated as interchangeable control and treatment arms. The registry record does not report a protocol-level statistical analysis plan or explain how the crossover observations were handled analytically.

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.

Only the first 6 of 8 groups are shown.

Overall Study

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With a Predicted Effect on αVβ6 PET ( Positron Emission Tomography) in Lungs After Administration of Drug., measured over Following 1 day of dosing.

The primary endpoint is the number of participants with a predicted effect on αVβ6 PET in the lungs after study drug administration. The timeframe is following one day of dosing. The endpoint description says PET tracer binding to the αvβ6 integrin receptor was quantified before and after administration of study drug, and that PK/PD modeling was used for the assessment.

PET imaging can provide a way to assess target engagement: in general, changes in tracer binding may be used to examine whether a drug is associated with changes at its intended biological target. PK/PD modeling, in general, relates drug exposure to measured pharmacodynamic effects. These methods help define what the endpoint is intended to represent, but they do not by themselves establish a clinical benefit.

The endpoint is expressed as a participant count, not as a continuous change in PET measurement in the registry description. The registry record does not report the count, the definition or threshold used to classify a participant as having a predicted effect, or a numerical estimate of change in tracer binding. Without those details, the magnitude and precision of the primary result cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint count?

The primary endpoint is described as the number of participants with a predicted effect on αVβ6 PET in the lungs. A count endpoint records how many participants satisfy a defined condition; it is distinct from a continuous measurement such as an average change in PET signal. The registry describes before-and-after tracer-binding assessment and PK/PD modeling, but does not report the criterion that turned those measurements into a participant-level predicted effect. It also does not report the resulting count. The endpoint's numerical result and the reproducibility of its classification therefore cannot be evaluated from the registry record.

What can a crossover design tell us?

General explanation: in a crossover study, a participant can receive more than one treatment or dose under different study conditions, allowing observations within the same participant to inform the comparison. That structure does not automatically make comparisons unbiased. Interpretation can depend on treatment sequence, timing, changes over time, and whether effects from an earlier exposure persist into a later period. These are general considerations, not claims about what occurred in this study. The registry records a crossover model but does not report the sequence or analysis details needed to judge these issues.

The allocation is also explicitly non-randomized and masking is recorded as none. In general, random allocation can help balance measured and unmeasured differences between groups, while masking can reduce some forms of expectation-related influence. Their absence means the listed groups should not be treated as a randomized, masked comparison. The registry itself cautions that the arms are not a like-for-like control comparison.

How should uncertainty be understood?

General explanation: an estimate describes the observed result, while a confidence interval expresses the range of values compatible with the data under the method's assumptions. A narrower interval indicates greater precision than a wider interval, but neither an estimate nor an interval alone establishes clinical importance. The registry record does not report a numerical primary estimate or confidence interval. It also lists 0 analyses, so no inferential analysis is available in the record to interpret alongside the endpoint.

General explanation: a p-value, when reported, evaluates how compatible data are with a specified statistical model and null hypothesis. It is not the probability that a treatment works, nor a measure of effect size. No p-value or hypothesis-test result for the primary endpoint is reported in the registry record. The record also does not report a prespecified hypothesis or the statistical model used to test the primary endpoint.

What do the planning assumptions mean?

The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe detecting a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed using those assumptions. The registry record does not report the trial's own sample-size justification, and the planning illustrations should not be read as observed power or as a substitute for an uncertainty interval around a result.

General explanation: over-dispersion occurs when the variability in count data exceeds what a simple count model expects. It can affect standard errors and uncertainty estimates if not handled appropriately. The primary endpoint is a participant count, but the registry record does not report a model for that count or any assessment of over-dispersion. No claim can therefore be made about whether it was relevant or how it was addressed.

What is available for safety?

The adverse-event entries are counts within the recorded groups: participants at risk, participants with serious adverse events, participants with other adverse events, and deaths. These counts are descriptive. General explanation: event counts from small groups can be unstable, and a zero recorded event does not establish that the underlying risk is zero. Because the registry groups include both single-dose and combined-dose labels, and the record gives no randomized comparison, the counts should not be combined into a treatment contrast or interpreted as comparative rates.

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("60 mg", "120 mg and 240 mg", "320 mg", "240 mg and 320 mg", "320 mg and 120 mg", "80 mg and 240 mg")
n      <- c(1, 1, 1, 2, 1, 1)
events <- c(1, 1, 0, 2, 1, 1)
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  60 mg  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  120 mg and 240 mg  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  320 mg  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  240 mg and 320 mg  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  320 mg and 120 mg  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  80 mg and 240 mg  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan for the primary and secondary outcomes, or for any dose-related comparisons. It does not state whether an outcome hierarchy, adjustment method, or other strategy was used to address the possibility of multiple statistical tests. Without that information and without reported inferential analyses, the family of hypotheses and the interpretation of statistical significance cannot be assessed.

Missing-data handling is not reported in the registry record. The record does not describe how missing PET measurements, incomplete dosing, or unavailable adverse-event information were handled. It also does not report analysis populations, such as which participants or observations were included in the primary endpoint analysis. The enrollment of 9 is recorded, but the record does not provide participant flow or an accounting of the observations contributing to each outcome.

The registry lists 0 analyses. This means no analysis results are posted in the record; it does not establish what analyses may have been conducted outside the registry. Interim analyses are not reported in the registry record. Nor is a prespecified statistical analysis plan reported. These omissions make it impossible to assess the planned handling of multiplicity, missingness, or analysis populations from the registry record alone.

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 non-serious adverse event terms

The serious adverse-event entries are zero for every listed group. The group entries report one participant at risk for 60 mg, 120 mg and 240 mg, 320 mg, 320 mg and 120 mg, 80 mg and 240 mg, and 80 mg and 120 mg; the 240 mg and 320 mg group reports two participants at risk. No serious adverse events are listed in any of these groups, and no deaths are listed.

For other adverse events, the record lists one event in the 320 mg group and one in the 80 mg and 240 mg group. The other listed groups report zero. These are counts, not comparative rates. The groups are small, and some labels combine dose levels, so their entries should not be added together or interpreted as independent randomized arms. The registry record does not give event descriptions beyond stating that there are no top serious terms.

A zero count means no event was recorded in that group in the posted results; it does not establish absence of risk. The safety entries should be read as descriptive observations, not as proof of safety or as evidence that one dose is safer than another.

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

The registry record describes an imaging study of target engagement: it assessed PET tracer binding to αvβ6 in the lungs before and after PLN-74809 administration and used PK/PD modeling. The primary question was expressed as a participant count with a predicted PET effect following one day of dosing. This gives readers context about the biological measurement the study was designed to examine.

The record does not report the numerical primary endpoint result, the effect size, or an uncertainty estimate. It therefore does not establish how many participants had a predicted effect or how precisely any effect was estimated. The absence of a posted analysis also prevents assessment of statistical evidence for the primary outcome. No conclusion about the magnitude of the PET response can be drawn from the registry record alone.

Target engagement is a measurement of a biological response at or near a proposed target. In general, such a measurement is not itself a measure of how participants feel, function, or experience a clinical outcome. The registry record does not provide a clinical efficacy result that would connect the imaging endpoint to a patient-level benefit. The statistical description should remain limited to the imaging endpoint and the safety counts actually reported.

The safety entries list no serious adverse events and no deaths in the recorded groups, with one other adverse event in each of two groups. These small descriptive counts cannot establish comparative risk. The non-randomized crossover design and lack of a like-for-like control comparison further limit any between-group interpretation. These results should not be read as evidence that a treatment works or does not work; the registry record lacks the primary numerical outcome and analysis needed for that assessment.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary outcome links an imaging measurement with a participant-level prediction. The endpoint description refers to PET tracer binding before and after study drug administration, with PK/PD modeling used to assess a predicted effect on lung αVβ6. That approach asks a target-engagement question rather than directly reporting a clinical outcome.

The crossover model can be useful for collecting repeated observations within participants, but interpretation depends on design and analysis details such as exposure sequence and timing. Those details are not reported in the registry record. The non-randomized allocation and absence of masking also matter: the listed groups are not randomized control and treatment arms, and the record cautions against treating them as a like-for-like comparison.

The gap between the stated endpoint and the posted results is important. The record describes what was measured but does not report the participant count, a numerical PET estimate, or an uncertainty interval. Without those, readers cannot assess the size or precision of the observed response. The safety information is also descriptive, with very small at-risk counts in each listed group.

For biostatistical interpretation, the record is a reminder that an endpoint definition and a completed study status do not replace outcome estimates, analysis methods, and uncertainty measures. Transparent reporting of those elements is necessary to evaluate what the data show and how strongly they support a 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 principal limitation for interpretation is that the numerical primary endpoint result is not reported in the registry record. The record does not give the number of participants with a predicted PET effect, a continuous PET estimate, or an uncertainty measure. It also does not state the criterion used to classify a participant as having a predicted effect. The primary outcome's magnitude and precision therefore cannot be evaluated.

The design is non-randomized, unmasked, and crossover. The registry cautions that the arms are not a like-for-like control comparison. The record does not report treatment order, period details, or how repeated observations were analyzed, limiting assessment of crossover-specific issues. The listed groups include both individual dose levels and combinations, which also complicates simple group comparisons.

The registry record lists 0 analyses and does not report an analysis plan, sample-size justification, multiplicity approach, missing-data method, or analysis populations. It does not report interim analyses. These omissions mean the intended statistical procedures and the handling of incomplete data cannot be evaluated from the record.

The safety counts are based on groups with one or two participants at risk. They are descriptive and too limited in the registry record to support comparative rate estimates. The record does not provide event details for the other adverse events, and no top serious terms are listed. These limitations concern what can be concluded from the posted record; they do not establish what may have been measured or analyzed outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2a Evaluation of PLN-74809 on αvβ6 Receptor Occupancy Using PET Imaging in Participants With IPF/ — NCT04072315.
• Registry record last updated 2023-12-12; status last verified 2023-11.
• Results first posted 2023-12-12.
• 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 record identifies a completed phase 2a, non-randomized, unmasked crossover study of PLN-74809 in participants with idiopathic pulmonary fibrosis, with enrollment of 9. It describes dose levels of 60 mg, 80 mg, 120 mg, 240 mg, and 320 mg and use of a knottin tracer for αVβ6 PET imaging.

The primary endpoint was the number of participants with a predicted effect on lung PET after one day of dosing. Its description refers to before-and-after tracer-binding quantification and PK/PD modeling. The numerical primary result and inferential analyses are not reported in the registry record. The record lists safety and tolerability as a secondary outcome.

No serious adverse events or deaths are listed in the recorded groups. One other adverse event is listed in the 320 mg group and one in the 80 mg and 240 mg group. These counts are descriptive and do not provide a randomized safety comparison.