A Study to Determine the Safety of AV-1, an Antibody Being Developed for Treatment of Dengue, in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Determine the Safety of AV-1, an Antibody Being Developed for Treatment of Dengue, in Healthy Volunteers (NCT04273217), a randomized phase 1 study. The primary outcome is Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase 1a, randomized, triple-masked, sequential study with placebo control. The official title describes a double-blind study, while the registry’s masking classification is triple. The registry record does not identify which study roles were masked. It describes a single ascending dose study of AV-1 in healthy male and female adult subjects; the listed AV-1 doses were 30 mg, 90 mg, 250 mg, 500 mg, and 1000 mg.

Each AV-1 group received a single intravenous infusion at its listed dose on Day 1. Infusion duration was 1 hour. The placebo group received a matched single infusion on Day 1. The registry labels the study model as sequential, but the detailed rules for moving between dose levels, dose-escalation decisions, or stopping the study are not reported in the registry record.

The registry reports enrollment of 42, a start date of 2020-02-04, primary completion on 2021-07-08, and a completed status. The primary safety follow-up window was baseline up to Day 120 (± 5 days). The stated safety population included participants who received any amount of investigational product.

In addition to the laboratory-abnormality endpoint, the record lists pharmacokinetic outcomes for AV-1, including serum concentration exposure measures, maximum observed concentration, time to maximum concentration, apparent terminal half-life, clearance, and volume of distribution. The registry record does not report the detailed randomization procedure, allocation ratio, or dose-escalation criteria.

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.

Before assignment: On the first day of dosing in all cohorts, the first group in each cohort comprised 2 sentinel participants: 1 was randomly assigned to receive AV-1 and the other was randomly assigned to receive placebo. After the Investigator reviewed the safety data from the 72-hour post-dose period for the sentinel participants, the remainder of the cohort (5 participants randomly assigned to AV-1; 1 participant randomly assigned to placebo) were dosed at least 72 hours after the sentinel participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety population included all participants who received any amount of the investigational product.

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: The Safety population included all participants who received any amount of the investigational product.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs), measured over Baseline up to Day 120 (± 5 days).

The primary endpoint is the number of participants with clinical laboratory abnormalities reported as treatment-emergent adverse events. It covers findings in hematology, serum chemistry, coagulation, and urine parameters, from baseline up to Day 120 (± 5 days). The record defines a TEAE as an event that was not present before study-drug exposure, or an event already present that worsened in intensity or frequency after exposure, whether or not the investigator considered it related to study drug.

This endpoint is used to describe laboratory safety after exposure, including changes that investigators classify as adverse events. Counting participants rather than individual laboratory measurements makes the endpoint a participant-level safety measure: a participant is counted if they meet the stated event definition. It does not, by itself, describe the severity, duration, clinical importance, or cause of each abnormality. Those details are not reported for this primary endpoint in the registry record.

The registry identifies the endpoint and its timeframe but does not report the primary endpoint’s observed group counts or an analysis comparing AV-1 with placebo. The separate adverse-event counts should not be treated as results for this laboratory-specific endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary endpoint is a binary participant-level outcome: whether a participant had a qualifying clinical laboratory abnormality reported as a TEAE. The endpoint is expressed as a number of participants, rather than as a mean laboratory value or a count of every abnormal test result. In general, binary outcomes are often summarized by counts and proportions within groups. The registry record identifies the count-based endpoint but does not report its observed counts or proportions.

The event definition combines laboratory findings with an investigator’s TEAE reporting. The event must be new after exposure, or an existing event must worsen in intensity or frequency after exposure. The definition also makes clear that investigator assessment of drug relatedness is not required for an event to meet the TEAE definition. This is important when interpreting the endpoint: it is a report of qualifying events after exposure, not a direct measure of causation.

What can the reported counts establish?

Counts describe what was recorded in the trial groups. They can make the observed experience transparent, but by themselves they do not quantify uncertainty around the underlying event frequency or establish a treatment effect. A confidence interval is a statistical range reflecting uncertainty in an estimate under a specified method; it is not reported for the primary endpoint in the registry record. A p-value is a measure calculated under a specified statistical model and hypothesis; the record reports no analyses and no p-value for this endpoint.

General statistical interpretation should distinguish a descriptive group difference from an inferential comparison. A numerical difference between observed counts can arise from random variation, especially when groups are small. A formal comparison would require a defined estimand, analysis method, and handling of uncertainty. Those details are not reported in the registry record. No new comparison has been calculated from the adverse-event counts.

How should the sequential dose groups be read?

The record classifies the model as sequential and lists multiple AV-1 dose levels with a placebo group. This supports describing the trial as a study that assessed safety across listed dose groups. The record does not state the criteria used to advance between dose levels, the timing of any escalation decisions, or whether decisions relied on formal statistical boundaries. Those design details should not be inferred from the word “sequential.”

The listed counts can be read separately for each group. They should not be combined into an assumed pooled AV-1 result: the registry does not report a pooled comparison, and different dose levels represent different exposures. Pooling would also require a clear analysis rationale that is not reported in the registry record.

What is known about the analysis plan?

The study summary says that results are based on the clinical study report and statistical analysis plan. However, the statistical analysis details are not reported in the registry record. The record does not state which model or test was used for the primary endpoint, whether estimates were adjusted, how confidence intervals were constructed, or whether any interim analyses were planned or conducted. It also does not report a sample-size justification.

General methods considerations include choosing an analysis that matches the endpoint and the intended comparison, and reporting uncertainty as well as observed counts. If repeated measurements or clustered observations are analyzed, over-dispersion can matter: in general, over-dispersion means the data vary more than a chosen statistical model expects, which can make standard errors too small if not addressed. The registry’s primary endpoint is a participant-level count of participants with an event, and the record does not say that an over-dispersion model was used or was needed.

How do the pharmacokinetic outcomes differ?

The registry lists pharmacokinetic outcomes such as area under the serum concentration-time curve, maximum observed serum concentration, time to maximum concentration, apparent terminal half-life, total serum clearance, and terminal-phase volume of distribution. These describe aspects of exposure and concentration over time, rather than the participant-level laboratory safety endpoint. The registry record names these outcomes but does not provide their numerical results or analysis methods in the registry record reported for this analysis.

Sample-size calculations, when used in general, are planning illustrations based on assumptions about an effect, variability, significance level, and allocation. They are not observed trial results and are not “observed power.” The registry record does not report the trial’s own sample-size justification, and no sample-size result is interpreted as evidence about the study’s observed treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and names multiple pharmacokinetic outcomes in addition to the primary safety endpoint. When several outcomes are examined, the chance of at least one apparently unusual finding can increase. In general, multiplicity procedures can address that issue, but the registry record does not report whether any adjustment was planned or used. It also does not identify a hierarchy for interpreting secondary outcomes or state which outcomes were designated for confirmatory inference.

Missing-data handling is not reported in the registry record. The record does not describe whether any participants lacked laboratory assessments during the primary endpoint window, how missing measurements were classified, or whether any sensitivity analyses were performed. Without those details, the effect of missing information on the primary endpoint cannot be evaluated from the registry record.

The stated safety population included all participants who received any amount of investigational product. The registry does not report the analysis population used for each pharmacokinetic outcome or provide a detailed accounting of participants included in each analysis. The trial summary says that results were based on a clinical study report and statistical analysis plan, but the relevant population definitions and analysis procedures are not reported in the registry record.

The record reports no analyses. It therefore does not provide an inferential account of the primary endpoint, multiplicity adjustment, missing-data assumptions, or sensitivity to analysis choices. Those omissions limit how far the posted results can support comparisons among dose groups or between AV-1 and placebo.

11. 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 summary reports 0 affected participants in every listed group. The numbers at risk were 6 for AV-1 30 mg, 6 for AV-1 90 mg, 6 for AV-1 250 mg, 6 for AV-1 500 mg, 7 for AV-1 1000 mg, and 11 for placebo. The summary also reports 0 deaths in every group. These are counts observed in the registry record, not estimates showing that the underlying risk is absent.

The registry separately lists other adverse events, with affected-participant counts of 3, 3, 0, 1, 4, and 3 for AV-1 30 mg, AV-1 90 mg, AV-1 250 mg, AV-1 500 mg, AV-1 1000 mg, and placebo, respectively. These should be kept distinct from serious adverse events. They also should not be interpreted as the primary laboratory-abnormality endpoint: the primary endpoint’s group counts are not reported in the registry record.

Because the group counts are limited, zero serious events in the observed groups cannot rule out uncommon events or establish comparable risk. The record does not report confidence intervals or a formal safety comparison.

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

The posted results support a narrow description of what was recorded: the serious-adverse-event counts and deaths were zero in each listed group, and the registry reports varying counts of other adverse events across the groups. The primary endpoint, clinical laboratory abnormalities reported as TEAEs, is defined in the record, but its observed group results are not reported in the registry record. The available adverse-event counts therefore do not answer the primary endpoint question.

The counts do not establish that AV-1 caused or prevented any reported event. A TEAE is defined by its timing or worsening after exposure, regardless of whether the investigator considered it related to study drug. A comparison of event counts is also not, on its own, a statistical test or a precise estimate of the difference in underlying risks. The record reports no analyses, uncertainty estimates, or adjusted comparisons.

This trial was conducted in healthy adult volunteers and evaluated single infusions across the listed dose levels. It does not establish the safety profile in people with dengue, and it does not answer whether AV-1 is effective for dengue. The registry describes AV-1 as a potential dengue treatment under investigation, but the endpoints are safety and pharmacokinetic outcomes, not a clinical dengue-treatment outcome.

Interpretation should remain within the population, exposure, follow-up, and outcomes recorded for this study. The findings do not resolve uncommon or delayed risks beyond what the study could observe, and the registry record does not report enough detail to evaluate missing outcomes or the statistical analysis of the primary endpoint.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of early-phase safety assessment: it records adverse events across several AV-1 dose groups and a placebo group in healthy volunteers. In an early-phase setting, the principal interpretive task is often to describe what was observed and how much uncertainty remains, rather than to treat small group counts as definitive comparisons. Here, the registry reports group-level adverse-event counts but no inferential analyses.

The study also illustrates why endpoint definitions matter. The primary endpoint is specifically about clinical laboratory abnormalities reported as TEAEs, while the adverse-event summary separately reports serious events, deaths, and other adverse events. These categories are not interchangeable. A clear definition helps prevent general adverse-event counts from being misread as results for a narrower laboratory endpoint.

The listed dose levels make it important to keep dose groups distinct unless a justified pooled analysis is reported. The registry describes the design as sequential, but does not give the escalation rules or statistical decision criteria. Consequently, the counts can be described by group, while conclusions about dose trends or comparative safety would require information not reported in the registry record.

Finally, the trial’s healthy-volunteer population and single-infusion exposure define the reach of the evidence. Statistical interpretation depends not only on the observed counts, but also on who was studied, what was measured, how long follow-up continued, and how the analysis handled uncertainty. The registry’s limited analytical detail makes those boundaries especially important.

14. 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 most direct limitation is that the registry record defines the primary laboratory-safety endpoint but does not report its observed group counts or an analysis. The available adverse-event counts do not fill that gap because they are not identified as counts of clinical laboratory abnormalities reported as TEAEs. This prevents a direct statistical interpretation of the stated primary endpoint.

The adverse-event groups are small, as reflected by the reported numbers at risk of 6, 6, 6, 6, 7, and 11. Counts from groups of this size provide limited precision, particularly for uncommon events. Zero observed serious events or deaths should therefore not be interpreted as proof of zero risk.

The trial studied healthy adult volunteers receiving a single infusion, rather than people with dengue receiving treatment. The record does not establish how the observed safety profile would apply in a patient population or under a different exposure pattern. It also does not report detailed event descriptions, severity, duration, or investigator assessments of causality for the other adverse-event counts.

Further limitations arise from missing analytical detail. The registry does not report the primary endpoint analysis method, confidence intervals, p-values, missing-data handling, multiplicity approach, sample-size justification, or dose-escalation rules. Although the study summary refers to a clinical study report and statistical analysis plan, those details are not reported in the registry record. These omissions limit evaluation of precision, bias, and the basis for any dose-group comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Determine the Safety of AV-1, an Antibody Being Developed for Treatment of Dengue, in Healthy Volunteers — NCT04273217.
• Registry record last updated 2022-10-31; status last verified 2022-10.
• Results first posted 2022-10-31.
• 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.

18. Record Summary

NCT04273217 is a completed Phase 1a, randomized, triple-masked, sequential, placebo-controlled study of AV-1 in healthy volunteers. The registry reports enrollment of 42. Participants received a single 1-hour intravenous infusion on Day 1 at one of the listed AV-1 dose levels, or matched placebo.

The primary endpoint was the number of participants with clinical laboratory abnormalities reported as TEAEs from baseline up to Day 120 (± 5 days). Its observed results are not reported in the registry record. The adverse-event summary reports zero serious adverse events and zero deaths in each group, alongside group-specific counts for other adverse events. The registry reports no analyses, and it does not provide the statistical details needed for inferential interpretation of the primary endpoint.