Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children (NCT03596801), a randomized phase 1 study. The primary outcome is Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants).

2. Clinical Question

The broader study purpose was to evaluate infectivity, safety, and immunogenicity of the vaccine candidates in both populations. The listed secondary outcomes include illness among RSV-seronegative participants who experienced natural infection with wild-type RSV during RSV surveillance, and antibody measurements in that setting. Those aims are distinct from the primary short-term solicited adverse-event question. The registry record does not report comparative estimates for those secondary outcomes.

3. Trial Design

This was a randomized, quadruple-masked, parallel Phase I study of two recombinant live-attenuated RSV vaccine candidates and placebo. The registry lists an enrollment of 60 and a completed status. The recorded study start was 2018-06-29, and the primary completion date was 2024-04-25. The registry record does not report the method used to generate the random sequence, how allocation was concealed, or which roles were included in quadruple masking.

Participants were divided by RSV serostatus and age. Group 1 consisted of RSV-seropositive children from 12 to less than 60 months of age. Group 2 consisted of RSV-seronegative infants and children from 6 to less than 25 months of age. Within each group, the listed arms were RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, and placebo. All interventions were described as single doses at Day 0. The doses listed for Group 1 were 10^6.0 PFUs for RSV 6120/∆NS1 and 10^5.8 PFUs for RSV 6120/F1/G2/∆NS1. For Group 2, the listed dose for each vaccine candidate was 10^5.0 PFUs.

The primary endpoint was the number of RSV-seropositive participants with solicited adverse events by grade, measured through Day 10. The registry describes 21 outcome measures, but lists 0 analyses. It does not report a detailed statistical analysis plan, the allocation ratios, or a sample-size justification. The record’s enrollment figure should therefore be read as the registered enrollment, not as evidence of the number included in a particular endpoint analysis. The analysis populations and endpoint-specific denominators 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: Of the 100 participants that were screened, 60 met eligibility criteria, parent agreed to enroll and were inoculated with study product.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Study participants who were immunized were included.

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 Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants), measured over Measured through Day 10.

The primary endpoint counts RSV-seropositive participants who experienced solicited adverse events, classified by grade, through Day 10. The specified events are fever, otitis media, upper respiratory illness, lower respiratory illness, and cough without lower respiratory illness. The registry says that a participant was counted once in each event category, at the highest grade experienced for that category. Grades follow the protocol-defined scale from Grade 1, mild, to Grade 4, life-threatening.

Counting participants gives a direct description of how many people in each listed category experienced an event, while grading distinguishes events by severity. This is a safety-focused endpoint, appropriate to the study’s stated evaluation of candidate vaccines in a Phase I setting. It is not an endpoint of vaccine efficacy against RSV infection. Nor does a count alone describe how long an event lasted, when it began, or whether it was judged related to vaccination; those details are not reported in the registry record.

The endpoint is restricted to RSV-seropositive participants and the stated observation period. It should not be treated as a result for the seronegative group, or as a summary of every adverse event collected during the study. The registry record describes the endpoint definition but does not report its grade-specific counts. Consequently, the primary endpoint’s observed distribution cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, quadruple masked, and parallel. Randomization is a general design method intended to allocate participants to groups by chance, helping reduce systematic differences at assignment. Masking is generally intended to limit the influence of knowledge about assigned treatment on participant experience, care, or assessment. The registry does not describe how randomization or masking was implemented, so their practical conduct cannot be evaluated from this record.

What does the primary endpoint count?

The primary endpoint is a count of participants, rather than a count of every occurrence of an event. For each solicited adverse-event category, a participant appears only once, at the highest grade experienced in that category. This rule prevents repeated occurrences of the same category in one participant from being counted as multiple participants. It also means that a participant can be represented in more than one category if they experienced different types of solicited events. The categories are fever, otitis media, upper respiratory illness, lower respiratory illness, and cough without lower respiratory illness.

The grades run from Grade 1, mild, to Grade 4, life-threatening, using a protocol-defined grading system. Grading adds severity information that an overall event count would not convey. However, the registry record does not give the grade-specific counts, the criteria for each grade, or participant-level event histories. The endpoint therefore cannot be reconstructed or independently checked from the record.

Why distinguish counts from rates?

General statistical explanation: A count is the number of participants with an event in a group. A rate or proportion relates that count to a defined denominator. Interpreting group differences requires knowing which participants were eligible for the endpoint and which had outcome information. Denominators may differ across outcomes if eligibility, follow-up, or reporting differs. The registry provides risk denominators for its adverse-event summary, but does not report primary-endpoint denominators or explain the difference between some listed at-risk counts and the arm descriptions. Comparisons should therefore use the denominators defined for the specific outcome rather than assuming that every enrolled participant contributed to every analysis.

What can randomization and masking establish?

General statistical explanation: Random allocation can support a fair comparison by balancing measured and unmeasured baseline characteristics on average, although chance imbalances can remain, particularly in small studies. Masking can reduce certain forms of bias, but does not by itself guarantee complete follow-up or unbiased outcome ascertainment. These design features do not replace transparent reporting of outcome definitions, analysis populations, missing observations, and statistical methods. The registry record does not report baseline comparisons or enough implementation detail to assess these issues.

How should uncertainty be assessed?

General statistical explanation: An estimate describes the observed data; a confidence interval communicates uncertainty around that estimate under its statistical assumptions. In safety comparisons with participant counts, uncertainty depends on the number of observations and the number of events. Sparse counts can produce imprecise comparisons, and a zero recorded count does not prove that the underlying event risk is zero. The registry record does not report confidence intervals or comparative hypothesis tests for the adverse-event summary. The zero serious-event entries should therefore be read as observed counts, not as precise estimates of risk.

The registry reports 21 outcome measures and 0 analyses. It does not report a statistical analysis plan, including planned models, covariate adjustment, handling of repeated or missing observations, or any prespecified comparison structure. No such methods should be inferred from the randomized design alone. The endpoint is described as participant counts by grade, but the registry does not state whether formal arm comparisons were planned for that endpoint.

The sample-size planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a fraction of the observed effect. Those are planning assumptions, not trial design details. The registry does not report the study’s own sample-size justification. Such illustrations are not observed power and cannot repair absent outcome estimates or uncertainty intervals. The primary endpoint has several event categories and grades, and the record does not provide one reduced comparison for a single planning calculation.

General statistical explanation: Over-dispersion matters when observed variability is greater than a statistical model assumes; standard errors based on an overly restrictive model may then be too small. The record does not identify a model for the primary outcome, so there is no basis for saying that over-dispersion was assessed or that a particular correction was used. For participant counts in small groups, clear denominators and uncertainty reporting are essential regardless of the modeling approach.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes several solicited adverse-event categories and grades. Multiple categories create a multiplicity issue if separate statistical tests are used: with more tests, the chance of at least one apparently unusual result can increase. A prespecified strategy might identify one primary comparison, adjust for multiple testing, or present the results descriptively. The registry record does not report which approach, if any, was planned. Its description of the primary endpoint does not identify a single event category or grade as the sole comparison.

The registry lists 21 outcome measures and 0 analyses. It does not report a statistical analysis plan or results for the primary endpoint’s grade-specific categories. The approach to missing outcome data, incomplete follow-up, or participants excluded from particular analyses is not reported in the registry record. The endpoint-specific analysis population and denominator are also not reported. These omissions limit assessment of whether the reported counts represent all eligible participants, only those with available observations, or another analysis set.

For the adverse-event summary, the record gives at-risk counts and affected counts, but does not describe missingness or explain all denominator differences. In particular, the Group 1 placebo arm has 5 listed at risk for other adverse events, while the arm description identifies a placebo group without explaining that summary denominator. This should be treated as an unresolved reporting detail rather than filled in by assumption.

General statistical explanation: Missing data can affect interpretation when the likelihood of an unobserved outcome is related to a participant’s health, treatment assignment, or event experience. Sensitivity analyses can explore how conclusions might change under different assumptions, but no such analyses are reported in the registry record. Without a stated multiplicity plan and missing-data approach, the registry entries support descriptive reading of the recorded counts, not a formal claim of statistical significance.

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 registry’s adverse-event summary separates serious adverse events, other adverse events, and deaths. It reports zero serious adverse events in each of the six listed groups and zero deaths in each group. The at-risk counts for serious adverse events are 10, 10, and 10 in Group 1, and 13, 14, and 6 in Group 2. These are observed summaries, not proof that the underlying serious-event risk is zero.

For other adverse events, the registry lists affected counts of 4, 6, and 2 in the Group 1 arms, and 11, 9, and 4 in the Group 2 arms. The corresponding at-risk counts are 10, 10, and 5 for Group 1, and 13, 14, and 6 for Group 2. These aggregate counts are not the primary endpoint’s solicited adverse events by grade. They do not indicate which event types occurred, their grades, timing, duration, or relationship to vaccination. The registry does not explain the Group 1 placebo at-risk count of 5 for other adverse events.

Without confidence intervals or comparative analyses, the counts should not be interpreted as evidence that one arm had a higher or lower underlying risk. Small observed counts, including zero, can be imprecise. The registry record does not report the grade-specific results for the primary endpoint.

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

The record establishes the study’s design, populations, interventions, and stated safety endpoint. It describes a randomized, quadruple-masked, parallel Phase I study with two vaccine candidates and placebo, conducted in separate RSV-seropositive and RSV-seronegative age groups. It also defines the primary endpoint as solicited adverse-event counts by grade through Day 10 in the RSV-seropositive group. These details clarify what the investigators set out to evaluate, but do not by themselves establish the observed outcome.

The posted adverse-event summary records zero serious adverse events and zero deaths in each listed group, alongside counts for other adverse events. Those figures are limited to the recorded categories in that summary. They are not a complete account of the grade-specific primary endpoint and do not provide comparative estimates or measures of uncertainty. A zero recorded count is not the same as proof of zero underlying risk. The registry also does not report comparative outcome analyses for immunogenicity, infectivity, or natural infection outcomes.

This record therefore cannot establish whether either vaccine candidate performed better or worse than placebo on the primary endpoint, whether an observed difference would be statistically distinguishable from chance, or how precisely any effect was estimated. It also does not support conclusions about protection against RSV infection. The listed secondary outcomes describe questions about illness and antibody responses among participants with natural infection, but their results are not reported in the registry record.

General statistical interpretation: A trial result is strongest when the outcome definition, analysis population, denominators, effect estimates, and uncertainty are all reported. Design labels such as randomization and masking are relevant to the credibility of a comparison, but they do not supply missing results. The appropriate reading is descriptive: the record reports the design and certain adverse-event counts, while leaving the primary endpoint’s grade-specific findings and formal statistical comparisons unreported.

13. Why This Trial Matters Statistically

This study raises statistical issues common to early-phase vaccine research. It evaluates two candidates in populations separated by age and RSV serostatus, and uses placebo comparisons within those groups. Keeping those populations distinct matters because the study’s endpoint and doses differ by group. A single overall result could obscure differences in eligibility or outcome relevance across the seropositive and seronegative populations.

The primary endpoint is also structured across several event categories and severity grades. That detail can make safety findings more informative than a single overall count, but it increases the importance of complete reporting and a clear plan for interpreting multiple outcomes. The registry describes how participants were counted within each event category, yet does not report the grade-specific results or the analysis strategy for those categories. Without those details, the endpoint cannot be fully interpreted.

The adverse-event summary illustrates why counts must be read with their denominators and uncertainty. It reports no serious adverse events or deaths in the listed groups, but the absence of observed events does not quantify how precisely a risk has been estimated. The other-event summary also contains a Group 1 placebo at-risk count that differs from the arm description, with no explanation recorded. Transparent denominator definitions are central to fair comparisons.

Finally, the registry lists broad aims concerning infectivity, safety, and immunogenicity, but does not report comparative analyses for those aims. The study’s statistical value to readers consequently depends not only on its design, but also on accessible outcome counts, analysis populations, uncertainty estimates, and methods. The record supplies some descriptive safety information, while leaving key elements needed for statistical evaluation unreported.

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 main limitation for interpreting results is that the registry record does not report the grade-specific counts for the primary endpoint. Although the endpoint definition specifies event categories, grades, and a Day 10 timeframe, it does not give the results needed to compare arms or describe the distribution of event severity. The registry lists 0 analyses, and does not report confidence intervals, hypothesis tests, or other comparative estimates for the posted adverse-event summary.

The adverse-event summary is not interchangeable with the primary endpoint. It presents serious and other adverse-event counts, but does not identify the types, grades, timing, or relationship of the other events. It also does not explain why the Group 1 placebo arm has 5 at risk for other adverse events, while its arm description does not explain that denominator. The record does not report endpoint-specific analysis populations or explain missing observations and exclusions.

The registry describes the study as randomized and quadruple masked, but does not give implementation details for those procedures. It does not report the statistical analysis plan, sample-size justification, multiplicity strategy, or handling of missing data. Sample-size planning illustrations based on an observed effect are not a substitute for a reported design justification or outcome analysis, and should not be read as observed power.

Finally, the stated secondary outcomes concern natural RSV infection, symptoms, and antibody measures, but their results are not reported in the registry record. The available information therefore provides limited grounds for assessing comparative safety and does not permit statistical interpretation of immunogenicity, infectivity, or illness outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children — NCT03596801.
• Registry record last updated 2026-02-13; status last verified 2026-01.
• Results first posted 2026-02-13.
• 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

NCT03596801 is a completed randomized, quadruple-masked, parallel Phase I study of two recombinant live-attenuated RSV vaccine candidates and placebo. It enrolled RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age. The registry lists enrollment of 60 and a single-dose intervention at Day 0.

The primary endpoint was solicited adverse events by grade in RSV-seropositive participants through Day 10. The registry defines the event categories and grading approach but does not report the grade-specific primary outcome counts. The adverse-event summary records zero serious adverse events and zero deaths in all listed groups, as well as separate counts for other adverse events. No comparative analyses are listed. The registry record does not report outcome uncertainty estimates, a statistical analysis plan, or results for the listed secondary outcomes.