Study to Evaluate Safety and Activity of TRL345 in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Safety and Activity of TRL345 in Healthy Volunteers (NCT05408091), a randomized phase 1 study. The primary outcome is Incidence of Abnormal Physical Exam Findings.

2. Clinical Question

The central question is about safety monitoring in healthy volunteers, not whether TRL345 treats a condition. The primary outcome counts participants with clinically significant abnormal physical-exam findings that were reviewed. The record reports zero participants with this outcome in each of the two TRL345 dose groups and in the placebo group.

The study description also identifies safety, tolerability, pharmacokinetics, and pharmacodynamics as aims. Listed secondary outcomes concern pharmacokinetic measures after a single infusion and anti-drug antibodies. Those aims provide context for why the study collected information beyond physical-exam findings, but results for the listed secondary measures are not reported in the registry record. The registry summary mentions serum samples for ex vivo studies of concentration-dependent antiviral activity, but those studies do not change the interpretation of the posted primary outcome.

The comparison is descriptive in the available results. No formal estimate of a difference between TRL345 and placebo, uncertainty interval, or statistical test is reported in the registry record. The observed counts therefore describe what was recorded in these groups; they do not establish the precision of a treatment comparison.

3. Trial Design

This was a completed Phase 1, randomized, quadruple-masked, sequential study of TRL345 in healthy volunteers. Its official title describes a double-blind, single ascending dose study, and the intervention is a single intravenous infusion. The registry lists two TRL345 dose levels: 1 mg/kg and 10 mg/kg. The arm descriptions state that participants were randomized 6:2 between TRL345 and placebo at each dose level. The posted results list 6 participants in each TRL345 dose arm and 4 in the placebo group.

The sequential model and ascending-dose description indicate that the dose levels were considered in sequence, rather than as a parallel comparison of several active doses within one undifferentiated group. The registry record does not report further detail about the operational rules governing progression between dose levels. It also does not report a statistical plan explaining how dose-level comparisons were intended to be made.

The listed enrollment is 16. The study began on 2023-09-14, reached primary completion on 2024-12-23, and is marked completed. The registry identifies Trellis Bioscience LLC as the sponsor. These registry entries describe the study record and its status; they do not add information about how participants were followed or how the analysis dataset was formed.

The primary outcome was incidence of abnormal physical-exam findings over 11 weeks. The record also lists pharmacokinetic measures, including Cmax, Cmin, clearance, volume of distribution at steady state, and half-life, as well as assessment of anti-drug antibodies. Although these outcomes clarify the study’s broader measurement goals, their numerical results are not reported in the registry record.

Randomization and masking are design features intended to support fair comparisons and reduce the influence of expectations on conduct or assessment. They do not by themselves guarantee that groups are comparable in every respect, nor do they make a small set of observed counts precise. The record does not report additional details about allocation concealment, masking procedures, or the analysis populations.

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:

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.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Abnormal Physical Exam Findings, measured over 11 weeks.

The primary endpoint is the incidence of clinically significant abnormal physical-exam findings reviewed during an 11-week timeframe. It is expressed as a count of participants, so the outcome concerns whether a participant had a finding meeting the study’s clinical-significance criterion, rather than the number or severity of individual findings. The registry record does not define further how clinical significance was determined or how findings were classified.

Physical examination is a clinical assessment that can detect changes in health status during a study. In an early-phase study of healthy volunteers, this type of safety measure can contribute to a broad account of tolerability alongside other safety monitoring. It is distinct from pharmacokinetic outcomes, which describe drug concentrations and their behavior over time, and from immunogenicity outcomes, which assess anti-drug antibodies.

The posted results report zero participants with the primary outcome in the 1 mg/kg group, zero in the 10 mg/kg group, and zero in the placebo group. These are observed counts, not estimates of the probability of an abnormal finding in a broader population. With no reported uncertainty intervals or formal comparison, the counts alone do not show how precisely the groups’ underlying risks have been estimated.

The registry record does not report further details about the timing or frequency of physical examinations within the 11-week timeframe, the handling of missing assessments, or the analysis population used for this outcome. Those details would help readers understand exactly how the endpoint was ascertained and which participants contributed to the reported counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The results are counts of participants with binary outcomes. For the primary endpoint, each participant either met the recorded criterion for a clinically significant abnormal physical-exam finding during the 11-week timeframe or did not. The same general distinction applies to whether a participant experienced a serious adverse event, another adverse event, or death. A participant count is not the same as a count of individual events: one participant may experience more than one event, but the record’s reported safety figures are participants affected.

What does a zero count tell the reader?

A zero count means that no participants in the listed group were recorded as having the specified outcome in the posted results. It does not mean the outcome is impossible, and it does not by itself estimate the outcome’s frequency with high precision. In general, an observed count is one realization from a process that could produce different results if the study were repeated. The uncertainty around a count matters, particularly when the group is small or the outcome is uncommon.

For the physical-exam endpoint, the posted counts are zero in each TRL345 dose group and zero in placebo. These matching observations do not demonstrate equivalence. Equivalence is a statistical claim that requires a defined margin and an analysis designed to assess whether the difference is sufficiently small. Neither an equivalence margin nor such an analysis is reported in the registry record.

Why is there no two-arm estimate?

A comparison of binary outcomes can be expressed through a difference in proportions, a ratio of proportions, or another prespecified measure. Each approach needs an appropriate analysis plan and enough information to estimate uncertainty. The registry record indicates that values for a two-arm comparison of this binary endpoint were missing or not estimable. It does not report a comparison estimate, confidence interval, or p-value. The observed counts can therefore be described, but a formal contrast between TRL345 and placebo cannot be interpreted from the posted results.

In general, a confidence interval gives a range of values compatible with the data under a statistical model and communicates the precision of an estimate. A narrow interval suggests greater precision than a wide interval, while an interval spanning values that would support different conclusions signals substantial uncertainty. No interval for a treatment comparison is reported, so the precision of any comparative effect cannot be assessed from the registry record.

How should the design inform interpretation?

Randomization is intended to make allocation less dependent on participant characteristics or investigator choice. Masking is intended to limit the influence of knowledge about assigned treatment on study conduct and outcome assessment. These design features can strengthen a comparison when the study includes a prespecified analysis and reports it. They do not replace the analysis, and they do not eliminate uncertainty due to the number of observations, missing measurements, or the way outcomes are defined.

The study is described as sequential and single ascending dose, with 1 mg/kg and 10 mg/kg dose levels. This structure is relevant because dose levels are not simply interchangeable groups: the study’s purpose and sequence inform how the findings should be read. The exact rules for moving between levels, any planned dose comparisons, and the statistical handling of the sequence are not reported in the registry record. No assumptions about those rules should be made from the label alone.

What can sample-size planning illustrate?

In general, a sample-size illustration estimates how many participants might be needed to detect a specified effect under stated assumptions. Such an illustration is not observed power and does not tell whether a completed study has established a result. The registry’s stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Those are planning conventions, not evidence that the trial was designed or analyzed under those assumptions. The registry record does not report the study’s own sample-size justification.

When an observed effect is uncertain or cannot be estimated, planning based on that effect can also be difficult to interpret. A planning illustration should therefore be treated as conditional on its assumptions, not as proof that the study had adequate power. The sample-size illustration is not an observed result and cannot substitute for a reported comparative estimate with its uncertainty.

What about dispersion and repeated outcomes?

For count data, statistical methods may need to account for over-dispersion, which occurs when the variability in counts is greater than a basic model expects. That issue is general and is not a reported feature of this primary endpoint: the primary outcome is recorded as participants with an event, rather than a count of repeated events per participant. If each participant can contribute only an affected or unaffected status, binary-outcome methods are more directly relevant. The record does not describe methods for repeated or correlated observations.

Overall, the available results support a descriptive reading of the recorded counts. The registry record does not report the detailed statistical analysis plan, uncertainty estimates, or a formal comparison for the primary binary outcome, so more extensive inferential claims cannot be assessed.

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("Dose Level 1 - 1 mg/kg", "Dose Level 2 - 10 mg/kg", "Placebo")
n      <- c(6, 6, 4)
events <- c(0, 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  Dose Level 1 - 1 mg/kg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Dose Level 2 - 10 mg/kg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Placebo  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures and identifies 6 secondary outcomes as posted. The primary outcome is physical-exam findings; listed secondary outcomes include pharmacokinetic measures and anti-drug antibodies. When a study assesses multiple outcomes, the chance of obtaining at least one apparently unusual result can increase if each is tested separately. Statistical plans can address this multiplicity through prespecification, adjustment, or a hierarchy of outcomes. The registry record does not report whether any such strategy was planned or used.

No analyses are reported for the outcomes in the record used for this interpretation. In particular, the registry does not give comparative estimates or statistical tests for the primary outcome. Numerical results for the listed pharmacokinetic and immunogenicity outcomes are also not reported in the registry record. Without those results, readers cannot assess their estimates, precision, or relationship to the primary safety findings.

The record does not report how missing outcome data were handled, whether any participants had incomplete assessments, or which analysis populations were used. It also does not specify whether results were analyzed according to randomized assignment, treatment received, or another population definition. These distinctions matter because the included participants and the handling of unavailable measurements can affect the interpretation of outcome counts.

The registry record also does not report a detailed statistical analysis plan, a multiplicity procedure, or an interim-analysis plan. Their absence from the registry record should not be taken to mean that no such procedures existed; their status is not reported. Given the lack of reported comparisons and analysis details, the outcome counts are best read descriptively, without treating them as confirmatory tests.

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 figures are participant counts. The registry lists 6 participants at risk in the 1 mg/kg group, 6 in the 10 mg/kg group, and 4 in placebo. It reports zero participants affected by a serious adverse event in each group. Deaths are also reported as zero in each group.

The record separately lists other adverse events affecting 2 participants in the 1 mg/kg group, 2 in the 10 mg/kg group, and 1 in placebo. These counts are not the primary physical-exam endpoint and should not be treated as interchangeable with serious adverse events. The registry record does not provide the terms for these other events, their severity, timing, or an assessment of whether they were related to study treatment.

Zero serious events and zero deaths describe what was observed in the listed groups, not a guarantee that such outcomes could not occur. The number of observations limits how much can be learned about uncommon events, and no uncertainty intervals are reported. The safety figures therefore provide a descriptive account of the posted experience, rather than a precise estimate of comparative risk or proof of absence of risk.

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

The main result is a set of observed counts: zero participants with clinically significant abnormal physical-exam findings in each group during the 11-week timeframe. The safety record also reports zero serious adverse events and zero deaths in each group, with other adverse events affecting 2 participants in the 1 mg/kg group, 2 in the 10 mg/kg group, and 1 in placebo. These figures describe the posted observations for this study.

They do not establish that TRL345 has no safety risks, that the dose groups and placebo are equivalent, or that one dose is safer than another. Those conclusions require evidence beyond matching or small counts, including a suitable comparative analysis and information about uncertainty. No such formal comparison is reported for the primary binary endpoint. The record also does not report event descriptions or treatment-relatedness for the other adverse events.

The trial was conducted in healthy volunteers and is identified as a Phase 1 single ascending dose study. Its results therefore address the outcomes and participants recorded in this early-phase study; they do not directly answer questions about use in transplant patients. The registry summary says the study was intended to support dose selection and the design and conduct of a clinical study in transplant patients, but it does not report that study’s results.

The posted outcome information does not give numerical results for the listed pharmacokinetic measures or anti-drug antibodies. As a result, the record cannot be used to describe the observed concentration profile, clearance, half-life, or immunogenicity findings. The mention of ex vivo antiviral-activity studies in the study summary is background about the intended use of serum samples, not a reported efficacy result in the outcome counts.

The appropriate statistical reading is consequently narrow: the registry records no primary physical-exam events, serious adverse events, or deaths in the listed groups, while recording other adverse events in each group. The counts do not determine the underlying risk with precision and do not establish a treatment effect. The registry record lacks the comparative estimates, uncertainty measures, and fuller outcome results needed for broader conclusions.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between observing no events and establishing that an outcome is absent or equivalent across groups. A zero count is a real result for the participants and follow-up recorded, but it is not a precise estimate of what would occur in a larger or different population. That distinction is especially important when reading safety outcomes from a Phase 1 study with limited group sizes.

The registry lists randomized, quadruple-masked allocation and a sequential ascending-dose design. Those features matter because they describe how the study sought to structure comparisons and limit bias. At the same time, design labels do not replace reporting of estimates, uncertainty, and analysis methods. Here, the available primary result is descriptive: each group has a zero count, and a formal two-arm binary comparison is not reported.

The study also shows why a registry’s planned aims and posted numerical results must be kept separate. Pharmacokinetic and immunogenicity outcomes are listed, and the study summary describes ex vivo activity work as part of the rationale. But numerical results for those listed secondary outcomes are not reported in the registry record. Their presence in the study description cannot be treated as evidence of a particular pharmacologic or antiviral result.

Finally, interpretation depends on the population and outcome definition. The primary endpoint concerns clinically significant physical-exam findings in healthy volunteers over 11 weeks. It is not itself a measure of treatment benefit in patients, and the record does not support conclusions about patient outcomes. Recognizing these boundaries helps keep a descriptive safety record from being mistaken for a definitive comparative assessment.

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 posted primary findings are counts from groups listed as 6 participants at each TRL345 dose and 4 participants in placebo. These group sizes limit the information available about uncommon outcomes and the precision of comparisons. The absence of a reported confidence interval makes that uncertainty harder to quantify from the registry record.

The endpoint description says clinically significant abnormal physical-exam findings were reviewed, but does not report the criteria used to judge clinical significance, the frequency of examinations, or the process for adjudication. These details could affect how the endpoint was identified and interpreted. Handling of missing physical-exam assessments and the analysis population are also not reported in the registry record.

The record does not report a formal comparison for the primary binary outcome; it notes that values were missing or not estimable for a two-arm comparison. No p-value or between-group uncertainty estimate is available. It also does not report a statistical analysis plan or a multiplicity strategy, despite listing multiple outcome measures.

Results for the listed pharmacokinetic outcomes and anti-drug-antibody assessment are not reported in the registry record. The other adverse-event counts lack event terms, severity details, timing, and attribution. Thus, the posted counts cannot characterize the nature of those events or establish whether they were related to TRL345.

Finally, the study enrolled healthy volunteers and used a single ascending-dose design. Its results are specific to the recorded study context and do not directly describe outcomes in transplant patients. The record’s summary states that the study was intended to support later evaluation in transplant patients, but those later outcomes are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate Safety and Activity of TRL345 in Healthy Volunteers — NCT05408091.
• Registry record last updated 2026-06-25; status last verified 2026-05.
• Results first posted 2026-05-27.
• 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

NCT05408091 is a completed, randomized, quadruple-masked Phase 1 study of TRL345 in healthy volunteers. The registry lists a sequential, single ascending dose design, with intravenous infusions at 1 mg/kg and 10 mg/kg and placebo as comparator. The reported enrollment is 16, with study dates from 2023-09-14 to primary completion on 2024-12-23.

The primary outcome was incidence of clinically significant abnormal physical-exam findings over 11 weeks. The posted count is zero in each TRL345 group and zero in placebo. The adverse-event record reports zero serious adverse events and zero deaths in each group, with other adverse events affecting 2 participants at 1 mg/kg, 2 at 10 mg/kg, and 1 in placebo.

No formal two-arm comparison is reported for the primary binary outcome. Numerical results for the listed pharmacokinetic and immunogenicity outcomes, missing-data handling, analysis populations, and multiplicity procedures are not reported in the registry record. The available results therefore support a descriptive account of the recorded counts, not a precise comparative conclusion.