Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (NCT04565249), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0.

2. Clinical Question

The trial’s stated focus was safety, tolerability, and pharmacokinetics, rather than a clinical effectiveness comparison. The primary outcome counted participants with treatment-related adverse events and laboratory abnormalities. The registry record describes collection from signing the informed consent form until the Day 28 study visit.

The posted outcome value is 0 for the PLN-74809 40 mg group and 0 for placebo. No participants are recorded at the 80 mg or 160 mg dose levels, so the posted results do not provide observations for those planned doses. The trial was terminated, and the registry record reports enrollment of 6.

This small set of posted observations can describe what was recorded among the participants who received study treatment or placebo. It does not establish whether the groups differ, nor does it characterize safety at dose levels without participants. A comparative statistical analysis is not reported in the registry record.

3. Trial Design

The registry describes a randomized, parallel-group, placebo-controlled phase 2 trial. The official title calls it a phase 2a, dose-ranging evaluation and describes it as double-blind; the masking field separately lists quadruple masking. The record does not explain how these masking descriptions relate to one another. It identifies PLN-74809 and placebo as the interventions.

Three PLN-74809 dose levels are listed: 40 mg, 80 mg, and 160 mg. The posted arm results record 5 participants at 40 mg and none at either of the higher dose levels. The placebo arm records 1 participant. The primary-outcome description likewise states that 5 participants received PLN-74809 and 1 received placebo. No further account of allocation among the planned arms is reported in the registry record.

The study concerns acute respiratory distress syndrome associated with at least severe COVID-19. It began on 2020-10-22, has a listed primary completion date of 2021-06-01, and is marked terminated. The recorded enrollment is 6. These are registry entries and do not, by themselves, explain why the study ended or whether the planned procedures were completed.

The listed primary outcome is a participant count for treatment-related adverse events and laboratory abnormalities assessed by CTCAE V5.0. The outcome collection period runs from informed consent through the Day 28 study visit. The record lists one outcome measure and no posted secondary outcomes. A detailed protocol, recruitment history, reasons for termination, and an explanation of the final arm composition 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: 5 Participant received PLN-74809 and 1 participant received Placebo

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: Study was discontinued before completion of enrollment of Dose 1.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0, measured over Adverse events were collected from the time the participant signed the Informed Consent Form until the Day 28 study visit.

The primary endpoint counts participants with treatment-related adverse events and laboratory abnormalities assessed by CTCAE V5.0. It is a count of participants meeting the endpoint, rather than a measure of event severity averaged across a group or a time-to-event measure. Its stated collection period begins when a participant signs the informed consent form and ends at the Day 28 study visit.

Safety outcomes of this kind are used to describe adverse experiences and laboratory findings during a study. Counting affected participants gives a direct, readable account of whether such events were recorded in the observed groups. The endpoint combines treatment-related adverse events and laboratory abnormalities, so the count does not distinguish between those components in the posted result.

The registry records 0 participants for the PLN-74809 40 mg group and 0 for placebo. It does not provide additional participants’ results at the 80 mg or 160 mg dose levels. The endpoint definition and the recorded values do not provide event-by-event clinical detail or an estimate of how frequently such events might occur in a larger population. The registry record does not report a more detailed endpoint definition, separate results for laboratory abnormalities and adverse events, or an inferential analysis of the group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: A randomized trial assigns participants to study groups by chance. Randomization is intended to reduce systematic differences in group assignment, but it does not guarantee that groups will be similar in a very small study. The registry lists this study as randomized and parallel-group. It does not report the allocation procedure or any stratification factors.

What does the endpoint count?

The primary outcome is binary at the participant level: each participant either meets the stated condition of having a treatment-related adverse event or laboratory abnormality, or does not. The posted result is expressed as a number of participants, not as a rate per unit of time. The registry records 0 in the 40 mg group and 0 in placebo. It provides no participant-level data and no separate count for the two components of the combined endpoint.

General: A binary outcome can be analyzed by comparing the proportions of participants with an event in each group. Such a comparison depends on both the event counts and the group sizes. With very sparse observations, estimates can be unstable, and standard large-sample approximations may not perform well. No comparison estimate or inferential analysis for this endpoint is reported in the registry record.

What can group size tell us?

The primary-outcome record gives 5 participants who received PLN-74809 and 1 who received placebo, while the arm-level results show that the treated observations are at 40 mg. The 80 mg and 160 mg arms have no recorded participants. These unequal and limited group sizes constrain the information available for comparing the observed groups. A zero event count in a small group does not show that the event is impossible or that its population probability is zero.

General: The width of a confidence interval reflects the precision of an estimate. Small samples and rare events commonly yield imprecise estimates, even when the observed count is zero. No confidence interval is reported for the primary endpoint. The registry record also does not report a sample-size justification, so the intended precision or power for the safety outcome cannot be assessed.

What analyses are reported?

The registry lists one outcome measure and no analyses. It does not report a statistical analysis plan, model specification, hypothesis test, adjustment method, or analysis population definition. The trial title identifies a pharmacokinetic objective, but a pharmacokinetic result is not included among the posted outcomes described in this record. A numerical statistical comparison should not be inferred from the arm counts alone.

General: In a randomized study, an analysis may compare groups as assigned or according to treatment received, depending on its prespecified purpose and definitions. The registry record does not identify which analysis population was intended or whether all randomized participants are represented in the posted outcome. The safety description reports participants who received PLN-74809 or placebo, but that alone does not establish a complete analysis-population rule.

What do the planning assumptions mean?

The registry information describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says that the effect to detect is a stated fraction of the observed effect. The record does not include calculated planning sample sizes in the registry record for interpretation. Such illustrations, when present, are planning scenarios, not observed power and not evidence that the trial was designed to achieve a particular precision.

General: Power is a design property under specified assumptions, not a measure of whether a completed study has demonstrated an effect. Sample-size planning can be especially sensitive when it uses an effect estimated from sparse data. Because the registry record does not report the trial’s own sample-size justification or a completed comparative analysis, the planning assumptions should not be treated as the study’s protocol or as an explanation of its final enrollment.

General: Over-dispersion matters when count data vary more than a statistical model expects; accounting for it can affect uncertainty estimates. This primary endpoint is a participant count for a binary outcome, and the registry does not report an over-dispersed count model or any other fitted model. No model-based conclusions are available from the posted results.

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("PLN-74809: Dose Level 1 (40 mg)", "Placebo")
n      <- c(5, 1)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  PLN-74809: Dose Level 1 (40 mg)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Placebo  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no posted secondary outcomes. It reports no analyses. A multiplicity strategy for handling more than one statistical test is not reported in the registry record. Because no inferential tests are posted, there is no reported adjustment or unadjusted testing framework to interpret.

The record does not describe missing-data methods, imputation, or sensitivity analyses. The absence of recorded participants in the 80 mg and 160 mg arms is an observed feature of the arm listing, not an outcome value and not evidence of zero events at those doses. The registry does not explain why those arms have no participants.

The primary outcome description identifies 5 participants receiving PLN-74809 and 1 receiving placebo. The arm results place the treated participants at 40 mg. The registry does not provide participant-level data, an explicit analysis-population definition, or a reconciliation of randomized participants with those represented in each outcome. It is therefore not possible to assess whether all randomized participants were included in the posted endpoint or how any unavailable observations were handled.

General: Missing-data methods matter when outcomes are unavailable because the way missing observations are handled can affect estimates and their uncertainty. A blank or absent arm result should not be treated as a zero-event result. The registry’s lack of detail on missingness and analysis populations limits evaluation of how complete or representative the posted outcome counts are.

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: respiratory rate increased (100.0%), intestinal dilatation (100.0%), abdominal compartment syndrome (100.0%), ventricular tachycardia (100.0%), cardiac arrest (100.0%).

The serious adverse-event entries report that 3 of 5 participants in the PLN-74809 40 mg group were affected and that 1 of 1 participant in the placebo group was affected. The registry lists 0 deaths in the 40 mg group and 1 in placebo. For other adverse events, it records 5 of 5 participants affected at 40 mg and 1 of 1 in the placebo group. These are observed counts within very small groups, not reliable estimates of how often events would occur in a broader population.

The record also lists serious-event terms with percentages: Respiratory rate increased, Intestinal Dilatation, Abdominal Compartment Syndrome, Ventricular Tachycardia, and Cardiac Arrest are each listed as 100.0%; Respiratory Failure is listed as 40.0%. The registry does not report the group-specific denominators or further detail needed to interpret these term percentages as group comparisons. They should not be assigned to a particular treatment group without that information.

Serious-event counts, other adverse-event counts, and the primary endpoint are different summaries. The primary endpoint specifically concerns treatment-related adverse events and laboratory abnormalities. The safety listings do not establish causality, and no comparative safety analysis is reported in the registry record.

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

The posted primary result is a count of 0 participants meeting the combined endpoint in the 40 mg PLN-74809 group and 0 in placebo. It describes what was recorded during the specified collection period among the participants represented in those arms. It does not provide evidence about the 80 mg or 160 mg groups, which have no participants listed.

The result does not establish that the two groups have the same underlying risk. With 5 participants in the 40 mg arm and 1 in placebo, a small number of observations cannot characterize uncommon events precisely. The absence of a recorded event in these groups is not proof that such events cannot occur. No uncertainty interval or statistical comparison is reported in the registry record.

The separate adverse-event listings include serious events, other events, and deaths. Those figures are relevant safety descriptions, but they are not interchangeable with the primary endpoint’s count of treatment-related adverse events and laboratory abnormalities. The registry does not report enough detail to interpret the listed serious-event term percentages by group, and the counts do not establish that treatment caused an event.

The study was terminated. The registry record does not report why, whether the planned enrollment was reached, or whether termination affected outcome collection. It also does not report a detailed protocol, a statistical analysis plan, or posted pharmacokinetic results. These gaps limit what can be concluded about the intended analyses and the full study objectives.

Overall, the record permits a narrow description of the posted counts and the uneven representation of planned dose groups. It does not support a claim that PLN-74809 is safe or unsafe, or that it changes clinical outcomes. It does not establish effectiveness. Such conclusions would require evidence and analyses beyond the registry results; this account is limited to the recorded trial information.

14. Why This Trial Matters Statistically

This trial is statistically notable because its planned dose-ranging design is represented in the posted results by participants at only one PLN-74809 dose level. The registry lists 40 mg, 80 mg, and 160 mg, but records participants only at 40 mg. The placebo group has 1 participant. As a result, the posted data cannot provide a dose-response comparison across the listed levels.

The primary outcome is a safety count, and the recorded count is 0 in both groups with participants. That simple result illustrates an important interpretive point: identical observed counts do not demonstrate identical underlying risks. Small group sizes leave substantial uncertainty, and the registry reports no interval estimate or formal comparison to quantify it.

The safety record also shows why outcome definitions must be kept distinct. The primary outcome combines treatment-related adverse events and laboratory abnormalities, while the registry separately reports serious adverse events, other adverse events, and deaths. Reading one count as if it represented all the others would blur different classifications and questions.

The trial’s termination and lack of posted analyses add context to the limits of interpretation. The registry does not state why the study ended, how the observed arm composition came about, or what statistical plan was used. The record is useful for understanding what outcomes and groups were listed, but it does not answer broader questions about treatment effects or the precision of safety estimates.

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.

Several limitations are specific to the posted record. Enrollment is listed as 6, with 5 participants receiving PLN-74809 and 1 receiving placebo. The arm results show participants only at the 40 mg dose level; neither the 80 mg nor the 160 mg group has participants recorded. This sharply limits the scope of any interpretation across the planned dose range.

The trial is marked terminated, but the reason for termination and its consequences for enrollment or outcome collection are not reported in the registry record. The listed start and primary completion dates do not explain whether all planned follow-up was completed. The primary endpoint’s collection period runs through the Day 28 study visit, but the record does not report follow-up completeness for individual participants.

The registry provides a primary endpoint count but no comparative analysis, uncertainty interval, or analysis population definition. It does not report the statistical analysis plan, a sample-size justification, missing-data procedures, or sensitivity analyses. It also does not provide separate primary results for adverse events and laboratory abnormalities.

The safety entries list serious adverse events, other adverse events, deaths, and serious-event terms, but the registry does not give enough detail to link all listed terms and percentages to treatment groups and denominators. These entries therefore cannot support a detailed group-level assessment of specific event patterns. No pharmacokinetic results are included among the posted outcomes described in the record, despite that objective appearing in the trial title.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 — NCT04565249.
• Registry record last updated 2022-11-17; status last verified 2020-09.
• Results first posted 2022-11-17.
• 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

NCT04565249 is a randomized, parallel-group, placebo-controlled phase 2 trial evaluating PLN-74809 in acute respiratory distress syndrome associated with at least severe COVID-19. The official title describes a phase 2a dose-ranging study; the registry lists quadruple masking, while the title describes double-blinding.

The primary outcome counts participants with treatment-related adverse events and laboratory abnormalities assessed by CTCAE V5.0, collected from informed consent through the Day 28 study visit. The posted count is 0 in the PLN-74809 40 mg group and 0 in placebo. The record lists no participants in the planned 80 mg and 160 mg groups.

The registry reports serious adverse events affecting 3 of 5 participants at 40 mg and 1 of 1 participant receiving placebo, other adverse events affecting 5 of 5 and 1 of 1, and 0 deaths at 40 mg and 1 in placebo. No statistical analyses are reported. The study is marked terminated; the reason is not reported in the registry record.