Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection (NCT03656510), a randomized phase 2 study. The primary outcome is Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 5 (AUC[Day 5]).

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study of JNJ-53718678 in children with RSV infection. The record lists enrollment of 246 and status as terminated. The study began on 2018-11-29, and primary completion was recorded as 2022-04-18. The reason for termination is not reported in the registry record.

Participants were assigned to placebo, a low dose, or a high dose. The study involved two cohorts: hospitalized participants and outpatients. Different dose levels were used across age groups. The low-dose description specifies oral administration twice daily for 7 days; placebo was matched to the volume associated with the dose group. The record does not give the complete high-dose description, so its full age-specific dosing schedule cannot be characterized from the registry record.

The primary endpoint combined data from both cohorts. The primary analysis population was the Intent-to-Treat-infected set, comprising randomized participants who received at least one dose and had centrally confirmed RSV RNA above the specified assay threshold. The group sizes reported for the primary endpoint were 79 for placebo, 80 for low dose, and 72 for high dose. Those endpoint-specific sizes need not equal enrollment: the analysis population and available outcome data determine the reported group counts.

The registry record describes 49 outcome measures and four analyses, but does not report a complete statistical analysis plan, the reason for the reported number of analyses, or a sample-size justification. Allocation concealment details, stratification factors, and interim analyses 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: Intent-to-Treat-infected (ITT-i) analysis set included all randomized participants who received at least one dose of study drug and who had a centrally confirmed RSV RNA viral load of greater than or equal to (\>=) 1 log10 copies/mL above the lower limit of quantification (LLOQ) of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set were performed as randomized.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 5 (AUC[Day 5]), measured over Baseline through Day 5.

The primary endpoint is RSV viral-load area under the curve from immediately before the first dose through Day 5. AUC represents viral-load measurements accumulated across time over the stated interval; a higher value reflects a greater accumulated viral-load measure during that interval. The endpoint was measured using quantitative reverse transcription polymerase chain reaction in mid-turbinate nasal swab specimens, with units of log10 copies*day per milliliter.

A time-integrated endpoint can describe the overall viral-load course during a defined early treatment period rather than relying on a single measurement. It is therefore a way to summarize antiviral activity across repeated measurements. The registry record reports means and 95% confidence intervals for the placebo, low-dose, and high-dose groups. It specifies that both cohorts were combined for this outcome.

The record identifies the primary analysis population as randomized participants who received at least one dose and had centrally confirmed RSV RNA viral load at least 1 log10 copies/mL above the lower limit of quantification. This restriction focuses the endpoint analysis on participants meeting the stated infection and assay criteria. A direct between-group estimate, hypothesis test, and handling of missing measurements for this endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: what a mean and confidence interval describe. The endpoint is continuous, and the registry reports a mean for each group. A mean summarizes the measured values in that group; it does not tell the reader how individual participants' values were distributed. A 95% confidence interval describes uncertainty around an estimated mean under the statistical procedure used. It is not a range containing 95% of individual participants' values. The registry record does not specify the precise interval-construction method for this endpoint.

General: why a group contrast matters. In a randomized comparison, the treatment effect is ordinarily expressed as a contrast between groups, with an estimate and its uncertainty. Separate group means are useful descriptive summaries, but without a reported contrast they do not directly provide the uncertainty around the difference. The primary endpoint record gives group means and confidence intervals, but no between-group estimate, confidence interval for a contrast, or p-value. A formal comparison cannot be reconstructed from the posted means and intervals without additional information and assumptions.

General: interpreting AUC. AUC combines measurements across the stated time interval into an accumulated measure. This can capture the overall level and course of a repeatedly measured quantity, rather than emphasizing a single time point. Its interpretation depends on the measurement scale, sampling schedule, and analysis choices. The registry identifies qRT-PCR nasal-swab measurements and the interval from baseline through Day 5, but details of the schedule, transformation, and calculation procedure beyond the endpoint description are not reported in the registry record.

General: analysis populations. Randomization defines the initial assignment to groups, while an analysis population specifies which participants contribute to a particular analysis. The primary endpoint population was restricted to participants who received at least one dose and met the central RSV RNA threshold. That definition is not identical to a population containing every randomized participant. The record does not report how participants outside the infected analysis set were handled in other analyses, or whether any sensitivity analyses used a different population.

General: missing measurements. Missing data can affect a mean if participants with unavailable measurements differ from those with observed measurements. Methods such as imputation or model-based estimation can make different assumptions about missingness and can yield different results. The approach used for missing primary endpoint measurements, the amount of missing data, and sensitivity analyses are not reported in the registry record. The group counts alone do not reveal why participants may be absent from the endpoint analysis.

General: multiplicity. When many outcomes or comparisons are examined, the chance of obtaining an apparently unusual result by chance can increase. A prespecified hierarchy, family-wise error procedure, or false-discovery approach can address that issue, but each requires a stated analysis plan. The registry lists many outcome measures and some secondary comparisons, but a multiplicity strategy is not reported in the registry record. The posted unadjusted p-values for selected secondary outcomes should consequently be read as unadjusted exploratory quantities rather than as confirmatory evidence.

General: sparse binary outcomes. For an outcome recorded as an event or no event, a risk difference compares the event proportions between groups. Its confidence interval conveys uncertainty in that contrast. When event counts are small, estimates can be imprecise and intervals can be wide; a small p-value or a large-looking relative estimate is not guaranteed to represent a stable effect. The secondary clinical outcomes include small event counts in several groups, and their registry record does not report sponsor analyses for the comparisons shown.

General: planning illustrations. The posted planning illustrations are calculations based on observed secondary effects, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They show the participants per arm that would be required under stated planning assumptions for 80% or 90% power when targeting the full, 75%, or 50% observed effect. They are not the trial's original design justification, not a report of the trial's achieved power, and not evidence that any effect is real. The trial's own sample-size assumptions and justification are not reported in the registry record. Small observed event differences can produce very large planning requirements, while such illustrations remain sensitive to the assumed effect and event rate.

General: interpretation of p-values. A p-value measures how compatible data are with a specified null model under the assumptions of a test. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The secondary comparisons include unadjusted p-values, but no corresponding sponsor-reported analyses are listed. The registry record does not identify a prespecified testing hierarchy for these outcomes. Conclusions should therefore consider estimates and uncertainty, the analysis population, the outcome context, and multiplicity rather than treating a single threshold as a decision rule.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 49 outcome measures and 48 secondary outcomes, and selected secondary comparisons have unadjusted estimates and p-values. A prespecified testing hierarchy, multiplicity adjustment, or distinction between confirmatory and exploratory hypotheses is not reported in the registry record. Without such information, the nominal p-values cannot be interpreted as controlling the overall chance of false-positive findings across the outcomes and comparisons.

The primary endpoint has group means and confidence intervals but no reported direct contrast or p-value. The record does not say whether an inferential comparison was planned but omitted from the registry results, whether the endpoint was descriptive, or what primary hypothesis was tested. The reason for termination and whether termination affected planned analyses are also not reported in the registry record.

The primary analysis set is defined as randomized participants who received at least one dose and met a central RSV RNA threshold. The number analyzed differs by group, but reasons for exclusion or missing endpoint data are not reported in the registry record. The handling of missing viral-load measurements, any imputation, and sensitivity analyses are also not reported. There is no basis in the record to determine whether missingness was similar across groups or whether it could have affected the estimates.

The registry record does not report a detailed statistical analysis plan, assumptions for the primary endpoint, covariate adjustment, interim analyses, or sample-size justification. The posted sample-size illustrations for selected secondary comparisons are planning calculations based on observed effects, not the trial's original design assumptions and not observed power. These gaps limit assessment of prespecification, the handling of incomplete data, and the strength of confirmatory claims.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (4.0%), bronchitis (3.2%), gastroenteritis (3.2%), asthma (3.2%), bronchiolitis (2.9%).

The safety summaries separate serious adverse events from other adverse events and report counts by cohort and assigned group. In Cohort 1, serious adverse events affected 4 participants in the placebo group, 5 in the low-dose group, and 2 in the high-dose group. In Cohort 2, the corresponding counts were 2, 2, and 3. The numbers at risk are reported separately for each group; the registry does not provide a statistical comparison of these safety counts.

No deaths are reported in any of the six cohort-by-group summaries. The record also lists selected serious adverse event terms, including respiratory failure, bronchitis, gastroenteritis, asthma, bronchiolitis, and coronavirus infection. The reported percentages for these terms are not a basis for attributing each event to a particular treatment group from the information in the registry record.

Counts describe what was recorded in this study; they do not by themselves establish whether an event was caused by treatment. Group sizes and follow-up matter when interpreting safety counts, and the record does not report a comparative safety model or adjusted analysis. The safety summaries should therefore be read descriptively, not as proof of a difference or of no difference between groups.

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

The registry results show the group-level mean RSV viral-load AUC through Day 5 and the uncertainty intervals around those means. The posted means are lower in the active-dose groups than in the placebo group, while the intervals overlap. This is a descriptive pattern, not a reported estimate of the treatment contrast. Because no primary between-group contrast or test is reported, the registry results do not quantify the comparative effect with its own uncertainty.

The result does not establish that the treatment has a clinically meaningful effect, nor does it establish that there is no effect. The record does not state a clinically meaningful threshold for the AUC measure. A lack of a reported contrast is not equivalent to a finding of no difference, and interval overlap is not a formal equivalence test. The evidence cannot be interpreted as demonstrating equivalence or noninferiority.

The primary endpoint concerns an early virologic measure. It does not, by itself, answer whether symptoms resolve sooner, whether hospitalization or intensive care is affected, or whether treatment is safe in every relevant respect. Secondary clinical summaries are limited and exploratory, with no multiplicity plan reported. Their interpretation also depends on distinct outcome definitions and follow-up windows.

The study included hospitalized participants and outpatients, but the primary result combines cohorts. The combined estimate does not show whether the result varies by clinical setting or age group. Cohort-specific primary results and interaction analyses are not reported in the registry record. The terminated status is relevant context, but its cause and analytic consequences are not described.

In general, a registry result is most informative when its analysis population, endpoint, group contrast, uncertainty, missing-data methods, and prespecified plan are clear. Several of those details are not reported for this trial. The posted data support a descriptive account of measured outcomes, but the available record does not justify a definitive causal or clinical conclusion.

13. Why This Trial Matters Statistically

This trial illustrates why a reported endpoint and a reported treatment comparison are not interchangeable. Means and confidence intervals allow readers to understand the scale and uncertainty of each group estimate, but the central comparative question requires a direct contrast with its uncertainty. Without that contrast, the primary summaries leave a material gap in statistical interpretation.

It also highlights the importance of specifying the analysis population. The primary viral-load measure was analyzed in an infected population defined by treatment exposure and a central assay threshold. That is a meaningful description of who contributed to the endpoint, but it differs from simply analyzing every randomized participant. Clear reporting of exclusions and missing measurements would help readers understand how well the analysis reflects random assignment.

The study's combined reporting across hospitalized participants and outpatients raises a further issue: an overall mean can conceal variation across clinically distinct settings. Cohort-specific estimates and a prespecified assessment of heterogeneity would help distinguish a common pattern from a result driven by one cohort. Such analyses are not reported in the registry record.

Finally, numerous outcome measures make multiplicity and reporting choices important. The selected unadjusted secondary comparisons are not confirmatory evidence in the absence of a reported multiplicity strategy and sponsor analyses. Planning illustrations based on observed effects are also distinct from the original sample-size rationale and from observed power. Together, these features show why trial interpretation depends on the full statistical plan and transparent reporting, not only on endpoint values.

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 primary endpoint is reported as group means with confidence intervals but without a direct comparison, contrast interval, or p-value. This prevents a complete assessment of the primary comparative question from the registry summaries. The method used to construct the confidence intervals is not reported in the registry record.

The primary results combine hospitalized participants and outpatients. No cohort-specific primary results or treatment-by-cohort analysis is reported, so the overall summaries do not establish whether the pattern is consistent across settings. The study also enrolled children across a broad age range with age-dependent dose levels, but age-specific endpoint results are not reported.

The registry lists many outcomes, but results are posted for only selected secondary measures. A multiplicity plan and a detailed statistical analysis plan are not reported. The reason for termination, any effect of termination on analyses, and the original sample-size justification are also not reported in the registry record.

Missing-data amounts, reasons for unavailable measurements, imputation methods, and sensitivity analyses are not reported for the primary endpoint. The endpoint-specific group sizes therefore cannot be fully reconciled with enrollment from the information in the registry record. Further, the registry does not report the full high-dose age-group dosing description, limiting a detailed account of that regimen.

Selected secondary clinical outcomes involve few events in some groups, making estimates potentially imprecise. Their unadjusted comparisons are not accompanied by sponsor-reported analyses in the registry record. Finally, the early virologic endpoint and the limited posted clinical summaries do not provide a complete account of longer-term clinical outcomes or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection — NCT03656510.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2023-09-21.
• 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.

18. Record Summary

This Phase 2 randomized, double-blind, placebo-controlled, parallel-group study evaluated different doses of JNJ-53718678 in children from 28 days through 3 years of age with RSV infection. It included hospitalized participants and outpatients, with enrollment of 246. The registry record lists the study as terminated.

The primary endpoint was mean RSV viral-load AUC from baseline through Day 5, measured by qRT-PCR in nasal swab specimens. The record reports group means and 95% confidence intervals for placebo, low dose, and high dose, but no direct primary treatment contrast or p-value. Selected secondary clinical outcomes and safety counts are also posted.

The reason for termination, the detailed analysis plan, primary missing-data methods, multiplicity strategy, and original sample-size justification are not reported in the registry record. The available results are descriptive and do not establish a definitive comparative conclusion.