Safety, Pharmacokinetics,and Antiviral Activity of RV299 Against Respiratory Syncytical Virus (RSV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Pharmacokinetics,and Antiviral Activity of RV299 Against Respiratory Syncytical Virus (RSV) (NCT06067191), a randomized phase 1 study. The primary outcome is Area Under the Curve (AUC) for RSV-A Memphis 37b Viral Load Determined by Quantitative Real Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group, placebo-controlled Phase 1 study. Its official title identifies it as Phase 1B. The study was conducted in an RSV viral challenge model, with RV299 compared with placebo. Both intervention descriptions specify a spray-dried dispersion for oral suspension. The record lists triple masking; the identities of the masked groups or roles are not reported in the registry record.

Enrollment was 82. The primary outcome analysis was defined for the Intent-to-Treat Infected population, which included randomized participants who received challenge virus and at least one dose of investigational medicinal product and met the RSV infection criterion. The primary outcome summaries include 23 participants in the RV299 group and 29 in the placebo group. Those analysis counts should not be treated as the total randomized enrollment: the registry record does not state the reasons for the difference in the counts.

The study's primary outcome was RSV-A Memphis 37b viral-load AUC measured by qRT-PCR, from initial administration through the morning of Day 12, described as quarantine discharge. The record also lists secondary measures of viral load, including peak viral load and viral-culture measures, as well as time-to-negative-test and time-to-peak outcomes. The registry record marks the study completed. The precise randomization procedure, treatment schedule, dose levels, and operational details of the challenge model 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.

Before assignment: A total of 82 healthy participants were enrolled in the study and received Respiratory Syncytial Virus (RSV) - A Memphis 37b virus inoculation (challenge agent) intranasally on Day 0. Three participants withdrew from study (2 withdrew consent and 1 not randomized because of influenza infection) before randomization and a total of 79 participants were randomized in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat Infected (ITT-I) Population consisted of all randomized participants who received challenge virus and at least 1 dose of IMP and met the criterion for RSV infection.

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: Safety population consisted of all randomized participants who received challenge virus and at least one dose of investigational medicinal product (IMP).

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve (AUC) for RSV-A Memphis 37b Viral Load Determined by Quantitative Real Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR), measured over From initial administration of IMP up to the morning of quarantine discharge (up to Day 12).

The primary endpoint is the area under the curve for RSV-A Memphis 37b viral load, measured in nasal washes by quantitative real-time reverse transcription polymerase chain reaction. AUC combines viral-load measurements across the stated follow-up interval into a measure of cumulative viral load over time. It is reported in hours multiplied by log10 copies per milliliter, and the registry lists the group means and standard deviations.

This endpoint is useful in a challenge study because it reflects the measured viral-load profile across the observation period rather than a single measurement. A lower AUC indicates a lower accumulated measured viral-load burden over that interval. It does not, by itself, describe every feature of infection, such as the timing of peak viral load or the time to a negative test; the registry lists those as separate secondary outcomes.

The interval began at initial administration of investigational medicinal product and continued up to the morning of Day 12, identified as quarantine discharge. The analysis population was restricted to randomized participants who received challenge virus and at least one dose of investigational medicinal product and met the RSV infection criterion. That definition matters when interpreting the result: the primary comparison is for this infected challenge-study population, not necessarily all randomized participants or the broader vulnerable populations named in the brief summary.

7. Results Posted in the Registry

• RV299: mean 350.99 versus 616.97 on control; difference -265.98 (95% CI -446.45 to -85.51), standardized effect d = -0.78; z-test p = 0.004.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Peak Viral Load of RSV Determined by qRT-PCR

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • RV299: mean 5.01 versus 6.23 on control; difference -1.22 (95% CI -2.24 to -0.20), standardized effect d = -0.66; z-test p = 0.019.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for RV299 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Area Under the Viral Load-Time Curve (VL-AUC) for RSV-A Memphis 37b Determined by Viral Culture

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • RV299: mean 106.48 versus 212.51 on control; difference -106.03 (95% CI -188.63 to -23.43), standardized effect d = -0.68; z-test p = 0.012.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for RV299 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Peak Viral Load of RSV Determined by Viral Culture

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • RV299: mean 2.43 versus 3.63 on control; difference -1.20 (95% CI -2.37 to -0.03), standardized effect d = -0.55; z-test p = 0.045.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for RV299 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the virologic description beyond cumulative qRT-PCR AUC. They include peak qRT-PCR viral load, viral-culture AUC and peak viral load, as well as listed time-to-negative-test and time-to-peak measures. The record posts numerical comparisons for several of these secondary endpoints; it does not provide numerical comparisons for every outcome named in the registry's secondary-outcome list.

Across the available continuous viral-load and viral-culture summary comparisons, the RV299 group means are lower than the placebo means. This general direction is compatible with the primary AUC pattern, but the secondary analyses are not uniform in how clearly their reported uncertainty supports a difference. In particular, the reported ANCOVA interval for peak viral load measured by viral culture includes zero. The secondary outcomes therefore provide contextual evidence, not a single interchangeable confirmation of the primary endpoint.

Each measure captures a different feature of the viral course. A peak value is a point-level summary, AUC aggregates measurements over time, and time-to-event outcomes concern when a defined testing threshold is reached. qRT-PCR and viral culture are also different measurement approaches. Agreement in direction across some measures may be informative, but it does not eliminate uncertainty about the size or interpretation of any individual contrast.

Secondary findings generally carry less inferential weight than the designated primary result when many outcomes are considered, especially if no multiplicity adjustment or hierarchy is reported. The record does not state whether secondary analyses were adjusted for multiple comparisons. Consequently, isolated secondary p-values should not be interpreted as if they were independently prespecified primary tests. The registry lists 26 secondary outcomes, while results are not numerically available in this record for all of the listed measures.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Peak Viral Load of RSV Determined by qRT-PCR
• Time to Confirmed Negative Test by qRT-PCR Measurement Starting From Initial Administration of Investigational Medicinal Product (IMP) to First Confirmed Undetectable Assessment After Peak Measure
• Time to Confirmed Negative Test by qRT-PCR Measurement Starting From Peak qRT-PCR After Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure
• Time to Peak qRT-PCR Starting From Initial Administration of IMP
• Area Under the Viral Load-Time Curve (VL-AUC) for RSV-A Memphis 37b Determined by Viral Culture
• Peak Viral Load of RSV Determined by Viral Culture
• Time to Confirmed Negative Test by Viral Culture Measurement Starting From at Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure
• Time to Confirmed Negative Test by Viral Culture Measurement Starting From Peak Viral Culture After Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary outcome estimate?

The primary outcome is continuous: each participant's viral-load AUC is a numerical measurement, and the registry reports group means with standard deviations. A mean difference expresses the average outcome in the RV299 group relative to the placebo group. For the recalculation, the difference is expressed as RV299 minus placebo, so a negative value indicates a lower average AUC in the RV299 group. This direction describes the data; it is not, by itself, a judgment about clinical importance.

A standard deviation describes how spread out individual measurements are around a group mean. It is not the uncertainty in the mean difference. Uncertainty in an estimated difference is instead reflected by its confidence interval and standard error. The posted means and standard deviations are summaries, so a recalculation from them cannot reproduce adjustments that may be included in the registry's ANCOVA analysis.

What does the ANCOVA result represent?

ANCOVA is a regression method that compares group outcomes while accounting for specified covariates. The registry reports a difference in least square means for this analysis. Least square means are model-based group estimates, and their contrast may differ from a direct subtraction of the observed group means. The record does not identify the covariates, model specification, or handling of missing observations, so those details cannot be assessed from the registry entry.

The posted unadjusted recalculation is a supplementary comparison based on the group summaries. It is not a replacement for the trial's reported analysis. For the primary outcome, both the unadjusted estimate and reported ANCOVA estimate point in the same direction, but their numerical values differ. The discrepancy flag is false, so the record does not identify a discrepancy between the posted analysis and this recalculation.

How should the confidence interval and p-value be read?

A confidence interval gives a range of values compatible with the data and the statistical procedure used, under its assumptions. It communicates uncertainty about the estimated contrast; it does not mean that every value in the interval is equally likely, and it does not establish the probability that a treatment effect is true. When an interval for a difference includes zero, the data are compatible with no difference under that interval procedure. When it excludes zero, the data are less compatible with zero under that procedure, but the interval does not establish clinical importance.

A p-value measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. The recalculated p-values are explicitly unadjusted. The registry's reported p-values belong to the reported ANCOVA analyses; the record does not say whether those p-values were adjusted for examining multiple outcomes.

Why can the analyses differ?

The recalculated primary contrast is formed from the posted group means. The registry's reported analysis is ANCOVA and reports a difference in least square means. Adjustment for covariates can alter the estimated contrast and its uncertainty. Since the covariates and model details are not reported in the registry record, the reason for the difference in numerical estimates cannot be determined. The estimates should be read according to the analysis that produced them, rather than treated as interchangeable calculations.

Standard errors describe the estimated sampling uncertainty of a statistic under a model. The posted recalculation includes standard errors for each group mean, but the central comparison is the mean difference and its confidence interval. Standard errors and confidence intervals depend on assumptions about the observations and the analysis. The registry record does not provide enough detail to evaluate those assumptions fully.

What is the role of the secondary outcomes?

The record lists secondary outcomes involving peak viral load, time to confirmed negative testing, time to peak, and viral-culture measurements. These measures address distinct aspects of the viral-load course and use different measurement scales. They can help describe whether the primary AUC pattern is accompanied by differences in other virologic features. They are not identical endpoints, and results for one should not be substituted for results on another.

When many outcomes are tested, some may appear unusual by chance even if there is no underlying difference for those outcomes. A multiplicity procedure can account for this, but whether one was prespecified or used is not reported in the registry record. Accordingly, unadjusted secondary findings should be treated as less definitive than a prespecified primary result. This general caution does not change the values reported for any particular endpoint.

11. Confidence Intervals and Precision

The primary unadjusted recalculation estimates an RV299-minus-placebo mean difference of -266.0 hours*log10 copies per milliliter. Its 95% confidence interval runs from -446.4 to -85.51. The interval excludes zero, which is consistent with lower average AUC in the RV299 group under this comparison. Its breadth indicates remaining uncertainty about the magnitude: values across a substantial range are compatible with the data and the method used.

The registry's ANCOVA estimate is -312.28, with a 95% confidence interval from -489.17 to -135.38. This interval also excludes zero. Because it is based on ANCOVA, it is a model-adjusted estimate rather than the same calculation as the unadjusted group-mean contrast. The record does not give enough model detail to explain the difference between the estimates or to independently verify the adjustment.

Confidence intervals are more informative about precision than a p-value alone because they show a range of estimated differences consistent with the data and method. Neither interval is a guarantee that the true effect lies within its limits. Both also concern the defined infected analysis population and the measured endpoint during the stated observation period. The group standard deviations are sizeable relative to the means, indicating substantial participant-to-participant spread in the outcome summaries; the interval reflects uncertainty in the group contrast, not the range of individual outcomes.

The secondary outcome intervals vary in width and in whether they include zero. That variation is relevant when judging how consistently the secondary analyses support a group difference. Confidence intervals do not resolve questions about multiplicity, the clinical meaning of a virologic difference, or applicability beyond the challenge setting.

12. 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 planning figures are participants per arm for 80% power and participants per arm for 90% power. They are planning illustrations based on the observed effect, not counts of participants enrolled or analyzed. For each effect assumption, the 80% power column describes a design with an 80% chance of detecting an effect of that assumed size under the stated planning model, if the effect and assumptions were correct. The 90% column describes a higher target chance of detection under the same kind of assumptions. Neither column is a measure of the power achieved by the completed trial.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The entries for continuous outcomes are participants per arm; time-to-event entries, if present, would give total events. The sample-size illustration is not observed power.

Planning for 100% of the observed effect uses the full observed effect as the target; planning for 75% or 50% uses smaller target effects. Smaller effects are harder to distinguish from random variation, so they require more participants under the same planning assumptions. Moving from the 80% target to the 90% target also generally requires a larger planned sample. These values are illustrative rather than the study's original design calculations. The trial's own sample-size justification and original design assumptions are not reported in the registry record.

13. 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 = -265.980; pooled standard deviation σ = 339.619.
2. n = 2 × (1.96 + 0.842)² × 339.619² / -265.980² = 25.6, rounded up to 26 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 <- -265.98                      # observed difference in means
sigma <- 339.618754922987                     # 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(6067191)
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 = 26 (80% power), 35 (90% power)
 75% of observed effect: n per arm = 46 (80% power), 61 (90% power)
 50% of observed effect: n per arm = 103 (80% power), 138 (90% power)
power.t.test: 26.6 
Simulated power at n = 26 per arm: 0.793 (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.

14. Analyses Reported by the Sponsor

The registry reports an ANCOVA comparison for the primary outcome: a difference in least square means of -312.28, with a 95% confidence interval from -489.17 to -135.38 and p < 0.001. This is the sponsor-reported analysis recorded for the outcome. It should be distinguished from the simple unadjusted recalculation from the posted group means, which estimates -266.0, with a 95% confidence interval from -446.4 to -85.51 and p = 0.004.

The recalculation is a transparent summary-statistic comparison, not an attempt to reproduce ANCOVA. The registry does not report the covariates or detailed model specification, so the adjusted result cannot be recreated from the means and standard deviations alone. The two estimates have the same direction, but their magnitudes and p-values differ because they represent different analyses. The record does not flag a discrepancy; the recalculation is therefore best read as a supplementary, unadjusted perspective alongside the reported analysis.

The same distinction applies to secondary outcomes: a simple group-summary contrast and a reported ANCOVA contrast are not necessarily identical. Interpretation should retain the analysis method attached to each estimate, rather than combining the two approaches or treating one as a correction of the other.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary AUC endpoint and lists numerous secondary outcomes, including different viral-load summaries, time-to-event measures, and viral-culture outcomes. Testing multiple outcomes creates a multiplicity issue: even when no real group differences exist, a collection of tests can produce some small p-values by chance. Methods such as prespecified testing hierarchies or adjusted significance thresholds can address this concern, but the use of such methods is not reported in the registry record.

The posted recalculation p-values are unadjusted. The registry reports ANCOVA results and p-values, but does not state whether these were adjusted for multiplicity. The record also does not report a statistical analysis plan or enough detail to establish which secondary analyses were confirmatory and which were exploratory. Thus, the primary endpoint should be distinguished from the wider set of secondary results, and secondary p-values should be read cautiously.

The primary analysis population is clearly described as the Intent-to-Treat Infected population: randomized participants who received challenge virus and at least one dose of investigational medicinal product and met the infection criterion. The record gives outcome group counts of 23 for RV299 and 29 for placebo. It does not describe missing-data handling, participant exclusions beyond the population definition, imputation, or sensitivity analyses. The reason these analysis counts differ from overall enrollment is not reported in the registry record.

The registry does not report whether interim analyses were conducted, whether early stopping rules existed, or whether any interim results informed the analysis. It also does not report the original sample-size justification or the full statistical analysis plan. These absences limit assessment of prespecification and robustness; they do not establish that particular procedures were or were not used.

16. 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

For serious adverse events, the registry lists 0 affected participants among 39 at risk in the RV299 group and 0 among 40 at risk in the placebo group. It also lists 0 deaths in each group. These are the reported counts for the safety groups; they should not be interpreted as proof that serious harms are impossible or that the groups have identical safety profiles.

The adverse-event groups have different counts from the primary outcome analysis population. The registry lists 12 participants with other adverse events in each group, among 39 at risk for RV299 and 40 at risk for placebo. These counts describe what is posted for those safety groups, not the frequency of every possible event or its severity, timing, or relationship to study intervention.

The registry does not list serious adverse-event terms among the posted serious-event terms. Safety interpretation is limited by the recorded counts and the study's challenge setting; the record does not provide enough detail to assess event definitions, follow-up beyond the reported period, or comparative risks with precision.

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

The primary result describes a lower average qRT-PCR viral-load AUC in the RV299 group than in the placebo group among participants meeting the registry's infected-population definition. Both the simple unadjusted estimate and the reported ANCOVA estimate are negative, and both reported 95% confidence intervals exclude zero. The data therefore show a group difference in this measured virologic endpoint under the analyses recorded.

The result does not by itself establish the clinical importance of the difference. AUC is a virologic measure collected over the challenge-study period, not a direct measure of symptoms, hospitalization, complications, or long-term outcomes. Although the brief summary identifies babies, older people, and bone marrow transplant recipients as vulnerable populations, the primary analysis concerns participants in a viral challenge model who met the infection criterion. The registry record does not establish that the result applies to those broader populations.

The findings also do not answer every question about antiviral activity. Peak viral load, time to negative testing, and viral-culture measures capture different features, and the posted secondary results have varying precision. Nor do the safety counts rule out uncommon harms: the registry lists no serious adverse events in the recorded safety groups, but those counts alone cannot establish the absence of risk.

Finally, the posted results concern the observed study population and time window. They do not establish outcomes beyond quarantine discharge or effects in settings other than the described challenge model. No treatment recommendation follows from these statistics alone; interpretation requires attention to the study design, analysis population, uncertainty, and limits of the recorded outcomes.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint, analysis population, and study setting must be read together. The primary endpoint is a cumulative viral-load measure, while the analysis population is restricted to randomized participants who received challenge virus and study medication and met the RSV infection criterion. Those choices define what the primary contrast describes. The total enrollment and the primary outcome counts answer different questions and should not be conflated.

It also demonstrates the distinction between an unadjusted summary-statistic recalculation and a model-based ANCOVA result. The primary estimates point in the same direction, but they are not numerically identical. Without the reported covariates and model details, the adjusted analysis cannot be reconstructed from the group means and standard deviations. Readers can therefore use the simple recalculation to understand the raw group contrast while retaining the reported ANCOVA result as a separate analysis.

The secondary outcomes show why a consistent direction is not the same as uniform evidence. Outcomes based on peak values, cumulative burden, timing, and different measurement methods are related but not interchangeable. Their uncertainty and multiplicity context matter. The record's missing detail on adjustment for multiple comparisons and analysis plans makes it particularly important not to elevate every secondary finding to the status of the primary result.

Finally, the safety counts and planning illustrations need appropriate scope. Zero recorded serious adverse events in the listed safety groups is a descriptive result, not proof of no risk. Planning figures based on the observed effect help illustrate how sample requirements change with assumed effect size, but they do not reveal the original design rationale or the power achieved in the completed trial.

19. 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 describes a viral challenge model and defines the primary analysis in an infected population. This limits direct generalization to the broader populations mentioned in the brief summary or to other clinical settings. The primary endpoint is virologic and measured through the morning of Day 12; the record does not establish clinical outcomes or effects beyond that period.

The primary group summaries include 23 participants for RV299 and 29 for placebo, while safety groups list 39 and 40 at risk. The record does not explain the difference between these sets of counts or report missing-data handling, exclusions beyond the stated analysis-population definition, or sensitivity analyses. These omissions limit evaluation of how participant availability may have affected the outcome estimates.

The reported ANCOVA analyses are not described in enough detail to evaluate model specification or reproduce the adjusted contrasts. Covariates, assumptions, and analysis-plan details are not reported in the registry record. Nor are the original sample-size justification, interim analysis procedures, or multiplicity methods reported. The secondary outcome list is broader than the set of outcomes with numerical comparisons available in this record.

The primary outcome estimates are compatible with a group difference, but the confidence intervals retain uncertainty about its magnitude. The secondary results are not equally conclusive, and the registry does not state whether their p-values were adjusted for multiple comparisons. The safety counts are descriptive and do not establish that uncommon or later events could not occur. These limitations should be considered alongside the measured endpoint and controlled challenge setting when interpreting the findings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety, Pharmacokinetics,and Antiviral Activity of RV299 Against Respiratory Syncytical Virus (RSV) — NCT06067191.
• Registry record last updated 2024-10-21; status last verified 2024-07.
• Results first posted 2024-10-21.
• 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.

23. Record Summary

The registry record describes a completed randomized, parallel, placebo-controlled Phase 1 study of RV299 in an RSV viral challenge model. The official title identifies the study as Phase 1B, and the record lists triple masking. Enrollment was 82. RV299 and placebo were both described as spray-dried dispersions for oral suspension.

The primary endpoint was RSV-A Memphis 37b viral-load AUC measured by qRT-PCR through the morning of Day 12 in the Intent-to-Treat Infected population. The posted summary means were 351.0 for RV299 and 617.0 for placebo. The reported ANCOVA difference in least square means was -312.28, with a 95% confidence interval from -489.17 to -135.38 and p < 0.001. The unadjusted recalculation was -266.0, with a 95% confidence interval from -446.4 to -85.51 and p = 0.004.

Secondary virologic outcomes and safety counts provide additional context, but their interpretation is limited by varying precision and unreported multiplicity and analysis details. The registry record does not report the original sample-size justification, interim analyses, or detailed ANCOVA specification.