A Two-Part Infant Study for Early Diagnosis of Respiratory Syncytial Virus (RSV) and Evaluation of JNJ-53718678 in RSV Acute Respiratory Tract Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Two-Part Infant Study for Early Diagnosis of Respiratory Syncytial Virus (RSV) and Evaluation of JNJ-53718678 in RSV Acute Respiratory Tract Disease (NCT04068792), a randomized phase 2 study. The primary outcome is Respiratory Syncytial Virus (RSV) Viral Load-time Curve From Immediately Prior to First Dose of JNJ-53718678 Through Day 5 (AUC [Day 1-5]).

2. Clinical Question

3. Trial Design

This was a Phase 2, two-part infant study with an observational stage followed by an optional interventional stage. The study focused on early RSV detection and disease kinetics, then on the antiviral activity and clinical outcomes of JNJ-53718678 in infants with RSV acute respiratory tract infection. The registry record lists an enrollment of 22 and describes the study as completed. The recorded start date is 2019-10-10 and the primary completion date is 2021-05-15.

In the observational stage, infants were closely monitored by parents or caregivers for early signs and symptoms with an RSV mobile application. An alert was intended to prompt testing. Participants in this stage were not to receive an intervention. The rationale in the study description was that monitoring might lead to diagnosis earlier than in a typical setting. The registry record does not report enough detail to characterize how often alerts led to testing or how early diagnoses occurred.

The second stage was an optional Phase 2a randomized, double-blind, placebo-controlled study. Its parallel-group structure compared JNJ-53718678 with placebo. The stated drug dose depended on age group, with 2.5 mg/kg for infants at least 28 days and under 3 months, 3 mg/kg for infants at least 3 and under 6 months, and 4.5 mg/kg for infants at least 6 months. The registry record does not report how many participants entered each study part or the number randomized to each age-specific dose.

The primary endpoint was RSV viral-load area under the curve from immediately before the first dose through Day 5. It used measurements from mid-turbinate nasal swab specimens assessed by quantitative reverse transcription polymerase chain reaction. The primary analysis population was restricted to randomized participants who received at least one dose and met the stated central viral-load confirmation threshold. The posted group counts for this outcome are 11 for placebo and 10 for JNJ-53718678. The registry record identifies 19 secondary outcomes as posted, including viral-load measures, time to undetectable viral load, and caregiver- or clinician-assessed severity measures.

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

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 viral load of greater than or equal to (\>=) 1 log10 copies per milliliter (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.

6. Primary Endpoint

The registry lists the primary outcome as Respiratory Syncytial Virus (RSV) Viral Load-time Curve From Immediately Prior to First Dose of JNJ-53718678 Through Day 5 (AUC [Day 1-5]), measured over Baseline (Day 1) up to Day 5.

The primary endpoint is RSV viral-load area under the curve from immediately before the first dose of JNJ-53718678 through Day 5, described as Day 1-5. It summarizes viral-load measurements over that interval rather than representing a single measurement at one time point. The assay was quantitative reverse transcription polymerase chain reaction, performed on mid-turbinate nasal swab specimens. The endpoint unit is log10 copies*day per milliliter, and the registry record reports group means with 90% confidence intervals.

As a general statistical concept, an area under the curve can capture both the level and the course of a repeatedly measured quantity over time. It can therefore provide a compact summary of a trajectory, while hiding details about when values changed or whether individual trajectories differed. Its interpretation depends on the measurement schedule, assay, and method used to construct the area; those details are not fully reported in the registry record.

Viral load is an antiviral endpoint: it measures the amount of viral material detected, rather than a direct measure of how an infant feels or functions. The study also listed clinical severity and other virologic outcomes as secondary measures, but the primary endpoint alone cannot answer every question about disease course, safety, or clinical outcomes. The primary analysis population further focuses the endpoint on participants who received study drug and met the central viral-load threshold. Findings should be understood in that defined population, not automatically generalized to all enrolled infants.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a mean, and the reported comparison is a mean difference in final values. A mean describes the arithmetic center of observed values, but it can be influenced by unusually high or low observations. The registry record gives the arm-specific means and their 90% confidence intervals, along with a 90% confidence interval for the mean difference. The method used to estimate these quantities is not reported in the registry record, so the statistical model and any adjustment for baseline or other factors cannot be characterized.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates more precision, while a wider interval indicates less precision. The interval for the mean difference runs from -4.467 to 2.416, including zero. That means the posted estimate does not distinguish clearly between a negative and positive mean difference at the interval's stated confidence level. It is not correct to interpret the interval as proving that there is no difference, and it does not establish equivalence in the absence of a stated equivalence margin.

The registry record reports a 90% confidence interval for the primary comparison. This is the interval level recorded for this endpoint; it should not be silently substituted with a different confidence level. The record does not give a p-value for the comparison. A p-value is a measure tied to a null hypothesis and a specified statistical procedure, but without a reported value or analysis method it cannot add information to the interpretation. The confidence interval itself communicates the estimate's uncertainty in the posted result.

Why use an area under the curve?

As a general statistical explanation, an area under the curve condenses repeated measurements into a summary of the level of a measurement over an interval. It can reflect the overall pattern rather than rely on one selected time point. This can be useful when a measure changes over time, as viral load may do during an acute infection. However, an area can conceal variation in the timing and shape of individual trajectories. Different trajectories can produce similar summaries, so the area does not fully describe the time course.

Interpretation also depends on how measurements were scheduled, how values below the assay's quantification limit were handled, and how the area was calculated. The endpoint description states that viral load was measured by quantitative reverse transcription polymerase chain reaction in nasal swab specimens, but the analytic details needed to evaluate these issues are not reported in the registry record. The listed unit, log10 copies*day per milliliter, identifies the scale of the area summary; it is not a direct clinical outcome.

What does the analysis population mean?

The primary population is described as Intent-To-Treat-infected. It includes randomized participants who received at least one dose and whose viral load was centrally confirmed at least 1 log10 copies per milliliter above the lower limit of quantification. This definition excludes randomized participants who did not meet those stated conditions from the primary analysis population. It is therefore a defined subgroup of randomized participants rather than an unrestricted analysis of every infant enrolled in the study. The number who were excluded, and the reasons for any exclusions, are not reported in the registry record.

As a general concept, restricting an analysis to participants with confirmed infection and measurable viral load can make the question more specific to participants for whom the antiviral endpoint is relevant. At the same time, results in such a population may not directly describe outcomes among all randomized or enrolled infants. The registry record does not report a separate analysis of all randomized participants, so comparison with such an analysis is not possible from the posted details.

How should planning illustrations be understood?

General sample-size calculations estimate the amount of information a future study might need under stated assumptions. The planning illustrations associated with this analysis use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not evidence about the design choices made for this trial. The registry record does not report the trial's sample-size justification or its own design assumptions.

Such planning figures are not observed power. Observed power would not make the estimated effect more or less credible after the data have been collected. A planning illustration can instead show how assumptions about the target effect relate to a prospective sample-size calculation. Any such illustration is especially dependent on the observed effect used as its starting point; uncertainty in that effect carries through to the planning exercise. The record does not provide a basis for treating an illustrative calculation as a prespecified trial objective.

In general, over-dispersion occurs when observed variation exceeds what a simple statistical model expects. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The registry record does not report whether over-dispersion was assessed or whether it was relevant to the primary analysis. No conclusion about that feature of the data can be drawn from the means and confidence intervals alone.

10. Analyses Reported by the Sponsor

The registry record posts a mean difference in final values of -1.03 for the primary comparison, with a 90% confidence interval from -4.467 to 2.416. It does not report a p-value or identify the statistical method used for this comparison. The displayed primary outcome includes the mean and 90% confidence interval for each group, as well as the between-group estimate and its interval. These are the sponsor's posted results as recorded in the registry.

No discrepancy is flagged between the sponsor's analysis and a recalculation in the available record. The posted sponsor analysis therefore remains the result to interpret; there is no stated conflict that would warrant favoring a separate recalculated estimate. A recalculation based on summary statistics, when presented, would be a simple unadjusted comparison and would not reproduce an analysis that might use participant-level data, adjustments, or other methods. The method for the sponsor's estimate is not reported in the registry record, so the precise relationship between methods cannot be assessed.

The key interpretation is unchanged: the reported interval includes zero and is broad, leaving uncertainty about the direction and size of the mean difference. Neither the point estimate nor a simple recalculation should be treated as proof of benefit, no effect, or equivalence. The registry record does not provide enough analytic detail to determine whether the sponsor used additional procedures beyond those described in the endpoint entry.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 19 secondary outcomes in addition to the primary outcome. These include viral-load measurements over time, change from baseline, viral-load area under the curve at other time points, time to undetectable viral load, and caregiver- or clinician-assessed severity measures. When a study examines multiple outcomes, time points, or comparisons, the chance of observing a seemingly notable result by chance can increase. As a general statistical principle, multiplicity procedures may control that risk, but the registry record does not report whether any adjustment was planned or used.

The primary result should therefore be distinguished from the broader set of outcomes. The presence of multiple registered outcomes does not establish that they were all analyzed in the same way, nor does the listed outcome count establish which findings were emphasized. The analysis plan, outcome hierarchy beyond the named primary endpoint, and any handling of repeated comparisons are not reported in the registry record. No conclusions about multiplicity adjustment can be inferred from the primary confidence interval alone.

Missing data are also important for a repeated-measure endpoint such as viral load over time. Missing measurements can affect the area-under-the-curve estimate, and different assumptions or methods for handling them can yield different results. The registry record does not report the amount or pattern of missing primary-outcome data, the imputation approach, or whether observations were excluded from the area calculation. It also does not report a sensitivity analysis assessing the impact of missingness. These omissions limit assessment of robustness.

The primary analysis population is defined by receipt of at least one dose and central confirmation of viral load above the specified threshold. This is not a full description of all randomized participants. The registry record does not report how many randomized participants failed to meet the definition, whether any randomized participants had no usable primary measurements, or how those cases were handled. It also does not report a separate intention-to-treat analysis including participants regardless of infection confirmation.

Consequently, the posted estimate applies to the stated Intent-To-Treat-infected population, subject to the unreported missing-data and analysis procedures. It should not automatically be generalized to all enrolled infants or all randomized participants. Details about multiplicity, missingness, exclusions, and analysis populations are needed to fully evaluate how the result fits within the complete outcome record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory syncytial virus bronchiolitis (9.1%), tracheobronchitis (9.1%).

The registry record lists serious adverse events for the safety groups as one participant in the placebo group and one participant in the JNJ-53718678 group. The number at risk is 11 in each group. Respiratory Syncytial Virus Bronchiolitis and Tracheobronchitis are each listed among the top serious-event terms, with 9.1% reported for each term. The record does not provide enough detail in this summary to determine the relationship between those terms and the serious-event participant counts, so the percentages should be read as posted rather than converted into additional counts.

Other adverse events are reported for 3 participants in the placebo group and 2 in the JNJ-53718678 group, with 11 at risk in each group. No deaths are listed in either group. These counts describe the recorded groups and should not be read as a complete characterization of the type, timing, duration, or severity of every event. The registry record does not report further event-level detail in this summary.

As a general principle, adverse-event counts in a small study are descriptive and have substantial uncertainty. They do not establish that one group is safer than another, and counts alone do not show whether events were caused by study drug, the underlying infection, or other factors. The posted serious-event figures should be considered separately from the primary viral-load endpoint. They do not determine the endpoint result or its interpretation.

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

The result answers a narrow statistical question: what mean difference in RSV viral-load area under the curve was reported between the randomized placebo and JNJ-53718678 groups in the primary Intent-To-Treat-infected population? The posted estimate is -1.03, with a 90% confidence interval from -4.467 to 2.416. The interval includes zero and remains compatible with differences in either direction. The data as posted do not identify the size or direction of the group difference precisely.

This does not establish that the groups are equivalent. Equivalence requires a prespecified margin and an analysis designed to evaluate whether the interval lies within that margin; neither is reported in the registry record. It also does not establish that there is no difference. A non-significant or uncertain result, especially without a reported p-value and with a broad interval, is not evidence that every clinically relevant difference has been ruled out.

The endpoint is virologic, not a direct measure of clinical benefit. A difference in viral-load area would not by itself show a difference in symptoms, complications, or other patient-centered outcomes. Conversely, the primary estimate alone cannot answer whether the early monitoring strategy led to earlier detection. The study had distinct observational and interventional stages, and the posted primary comparison concerns the drug and placebo groups in the interventional stage.

The analysis population also matters. The primary result pertains to participants who received at least one dose and met the central viral-load confirmation threshold. It should not be assumed to represent infants who were not randomized, did not receive a dose, or did not meet that threshold. The record does not report enough information to quantify how those groups differed or how missing outcome measurements were handled.

The posted safety counts are descriptive and do not establish comparative safety. The number of serious adverse events and other adverse events should be considered with the limited group sizes and the absence of detailed event-level analysis in mind. Overall, the registry result is an estimate with substantial uncertainty, not a standalone basis for broad claims about clinical outcomes, safety, or effectiveness.

14. Why This Trial Matters Statistically

This study is statistically notable for combining an observational early-detection stage with an optional randomized treatment evaluation. Those parts address different questions. Monitoring with a mobile application concerns the process and timing of recognizing possible RSV illness, while the randomized stage compares a drug with placebo among infants with RSV infection. Keeping the questions separate prevents the randomized viral-load comparison from being mistaken for an evaluation of the monitoring strategy.

The primary endpoint also illustrates a common design choice in antiviral research: summarizing repeated measurements over time with an area-under-the-curve measure. This can provide a single endpoint for a changing biological quantity, but its interpretation depends on measurement timing, assay methods, and handling of incomplete observations. The registry record specifies the assay and specimen type, while leaving important analytic details unreported. Those gaps matter when judging how reproducible or robust the estimate may be.

The confidence interval is central to interpreting the result. The point estimate alone would give an incomplete account; the 90% interval from -4.467 to 2.416 shows that the estimate remains compatible with different directions of effect. In a study with small outcome groups, this uncertainty is important. The result does not resolve whether a more precise comparison would show a meaningful difference, and it does not establish equivalence.

The record also provides a useful reminder that a registered set of secondary outcomes can be broader than the primary result. Viral-load kinetics, time to undetectable viral load, and assessments of signs and symptoms address related but distinct questions. Without complete results and information about multiplicity, they should not be used to overstate the primary finding. Clear separation of endpoint, analysis population, and uncertainty is essential for sound interpretation.

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 registry record does not report the statistical method used for the primary comparison, the model assumptions, or whether the analysis adjusted for baseline viral load or other characteristics. It gives the mean difference and 90% confidence interval but no p-value. This makes it difficult to independently assess the analysis or reproduce the sponsor's result from the registry summary alone.

Important details of the repeated viral-load measurements are not reported in the outcome description. These include the measurement schedule used in the area-under-the-curve calculation, the method for calculating the area, and the handling of values below the assay's lower limit of quantification. The description identifies the specimen and qRT-PCR assay, but does not explain how incomplete or irregular measurement trajectories were handled.

The primary population is restricted to randomized participants who received at least one dose and had centrally confirmed viral load at least 1 log10 copies per milliliter above the lower limit of quantification. The registry record does not report the number excluded by this definition or the reasons for exclusion. It also does not report a separate comparison in a broader randomized population. As a result, the applicability of the primary estimate beyond the stated analysis population is uncertain.

The study was described as having an observational stage and an optional interventional stage, but the record does not report how many infants participated in each stage or how many were randomized to each age-specific dose. The primary-outcome group counts are 11 and 10. Those counts do not describe the full flow of participants through the two-part study. The registry record also does not provide enough detail to assess adherence, withdrawals, or missing outcome data.

Finally, the record does not report the sample-size justification, an analysis plan for multiplicity, or whether any interim analyses were conducted. It lists 19 secondary outcomes, but the available result summary does not permit a full assessment of those findings. These omissions constrain interpretation of the primary estimate and the study's broader evidence on viral kinetics, clinical severity, and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Two-Part Infant Study for Early Diagnosis of Respiratory Syncytial Virus (RSV) and Evaluation of JNJ-53718678 in RSV Acute Respiratory Tract Disease — NCT04068792.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2022-06-08.
• 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

NCT04068792 is a completed Phase 2 infant study with an observational early-detection stage and an optional randomized, double-blind, placebo-controlled interventional stage. The recorded enrollment is 22. The study start date is 2019-10-10 and the primary completion date is 2021-05-15.

The primary endpoint was RSV viral-load area under the curve from immediately before the first dose through Day 5, measured by qRT-PCR in mid-turbinate nasal swab specimens. The primary analysis population was defined by receipt of at least one dose and centrally confirmed viral load above the stated threshold. The posted means were 26.13 for placebo and 25.1 for JNJ-53718678; the mean difference was -1.03, with a 90% confidence interval from -4.467 to 2.416.

The registry record lists 19 secondary outcomes. It also reports serious adverse events in one participant in each safety group and no deaths. The primary comparison is uncertain, and analytic details on missing data, multiplicity, and the statistical model are not reported in the registry record.