A Study on the Immune Response, Safety and the Occurrence of Respiratory Syncytial Virus (RSV)-Associated Respiratory Tract Illness After Administration of RSV OA Vaccine in Adults 60 Years and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Immune Response, Safety and the Occurrence of Respiratory Syncytial Virus (RSV)-Associated Respiratory Tract Illness After Administration of RSV OA Vaccine in Adults 60 Years and Older (NCT06551181), a randomized phase 3 study. The primary outcome is RSV-A Neutralizing Titers Expressed as Adjusted Geometric Mean Titers (GMTs) at 1 Month Post RSVPreF3 OA Vaccination.

2. Clinical Question

This is an immunogenicity question, not a direct comparison of clinical protection between the two populations. The study’s stated purpose was to evaluate the immune response in older adults in China against that in older adults enrolled overseas. Its brief summary refers to vaccine efficacy against lower respiratory tract disease in an earlier global efficacy study, but that prior study’s results are not analyzed by the primary endpoint. In the current study, the primary result is an antibody-titer comparison after vaccination, rather than an estimate of vaccine efficacy against illness.

The registry also lists safety outcomes for all participants and respiratory illness outcomes for China participants only. It explicitly states that overseas participants did not undergo acute respiratory illness surveillance. Consequently, the immune-response comparison and the illness-occurrence assessments address different populations and questions; they should not be treated as interchangeable evidence.

3. Trial Design

The registry describes NCT06551181 as a Phase 3, randomized, controlled, parallel-group study with quadruple masking. Its official title describes it as partially blind. These are the registry’s descriptions; further details about who was masked, how masking was maintained, or which procedures were partially blind are not reported in the registry record.

The study enrolled 2620 participants and is listed as completed. Its recorded start date is 2024-08-05, and its primary completion date is 2025-04-24. The registry lists RSVPreF3 OA investigational vaccine and saline placebo interventions. The overseas group received one vaccine dose at Day 1 and was followed through Month 6. The China vaccine and China placebo groups were followed through Month 6 or their last acute respiratory illness visit or contact, whichever was later.

The primary comparison uses the China vaccine group and the overseas vaccine group, not the China placebo group. The posted primary analysis includes 1175 participants in the China vaccine group and 757 in the overseas vaccine group. These are analysis counts for the reported endpoint, not the overall enrollment. The endpoint description says that the analysis used a Per Protocol Set, with eligibility based on receiving study intervention, having pre-dose and post-dose immunogenicity results, meeting blood-draw intervals, and having no intercurrent conditions or prohibited concomitant medication that could interfere with immunogenicity. Further details of the eligibility criteria are not reported in the registry record.

RSV-associated acute respiratory illness surveillance was conducted only in China. Thus, illness occurrence in China vaccine and placebo groups is not directly comparable with illness occurrence in the overseas group, for which surveillance was not conducted. The registry lists 20 outcome measures and 16 posted secondary outcomes. The protocol, detailed randomization procedures, allocation concealment, masking procedures, and the planned statistical analysis document 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: Analysis performed on Per Protocol Set(PPS)-all eligible participants who received study intervention,had immunogenicity results pre\&post dose,complied with blood draw intervals,without intercurrent conditions that may interfere with immunogenicity \& without prohibited concomitant medication.As pre-specified in Protocol,analysis was performed only on RSV OA vaccine (China) \& RSV OA vaccine (Oversea) groups.Participants with adjusted RSV-A GMTs data available at specified timepoint were reported.

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 RSV-A Neutralizing Titers Expressed as Adjusted Geometric Mean Titers (GMTs) at 1 Month Post RSVPreF3 OA Vaccination, measured over At Day 31.

The primary endpoint is the adjusted geometric mean titer of RSV-A neutralizing antibodies at Day 31, described as one month after vaccination. Neutralization titers are laboratory measurements of antibody activity against RSV-A. The registry says the titers were measured by a neutralization assay and that the analysis used an analysis of covariance model on log10-transformed titers.

A geometric mean summarizes measurements that are analyzed on a logarithmic scale and then expressed on the original scale. This approach is commonly used for antibody titers, which can vary substantially and are often analyzed multiplicatively. The adjusted GMT accounts for the model’s treatment-group term and the pre-dose log10 titer covariate, as described in the registry. It is therefore a model-based group summary, rather than simply the arithmetic average of the raw titers.

Day 31 is the specified primary time point. The endpoint focuses on the RSV-A response; the registry lists RSV-B titers and other immune and illness outcomes as secondary measures. Comparing adjusted titers between China and overseas participants addresses whether the measured immune response in the China vaccine group is sufficiently close to that in the overseas vaccine group under the study’s non-inferiority framework. Such an antibody endpoint can support an immuno-bridging assessment, but by itself it does not directly measure whether participants avoided respiratory illness. The non-inferiority margin and its justification are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis uses an analysis of covariance (ANCOVA) model. ANCOVA compares group outcomes while adjusting for a covariate. In this study, the outcome was the RSV-A neutralizing titer analyzed after log10 transformation, treatment group was included as a fixed effect, and pre-dose log10-transformed titer was included as a covariate. This adjustment aims to compare groups while accounting for measured differences in baseline antibody titers. The registry does not report additional model terms or diagnostics.

Why analyze titers on a logarithmic scale?

As a general statistical principle, antibody titers may be more naturally compared as relative rather than absolute changes. A logarithmic transformation can make a highly skewed distribution more suitable for a model and makes multiplicative relationships easier to represent. After modeling on the log scale, estimates can be transformed back to the original scale and expressed as geometric means. This general explanation does not establish whether the model assumptions were met in this study; diagnostic results are not reported in the registry record.

An adjusted geometric mean titer is a model-based summary, conditional on the covariate adjustment used. Here, the stated covariate is the pre-dose log10 titer. The adjusted group GMTs are 5677 for China and 6330 for overseas, with respective 95% confidence intervals of 5419 to 5946 and 5974 to 6706. These estimates are not raw arithmetic averages. The registry does not specify the exact covariate values or other details used to produce adjusted estimates.

What does the ratio represent?

A ratio compares the scale of one group’s geometric mean with that of another. The reported group GMT ratio is 1.11, and its 95% confidence interval is 1.04 to 1.20. The registry labels this ANCOVA result as a non-inferiority analysis. A confidence interval represents a range of values compatible with the data and the model under repeated use of the same statistical procedure; it is not a probability statement that the true value lies in this particular interval. The registry does not explicitly identify the ratio’s numerator and denominator, so the direction of the ratio should be interpreted alongside the group-specific GMTs and the stated comparison.

In a non-inferiority study, the objective is to assess whether the outcome in one group is not worse than the comparator by more than a prespecified margin. The margin and its clinical or statistical justification are essential to interpreting the formal decision. They are not reported in the registry record. The classification as non-inferiority is recorded, but the available result does not allow a reader to reproduce the decision rule without the margin and fuller analysis details.

What does a confidence interval add?

As a general explanation, a confidence interval conveys both the estimated effect and its statistical precision. A narrower interval indicates greater precision than a wider interval under the same model and confidence level. The ratio interval from 1.04 to 1.20 excludes 1, which is the value representing equal geometric means for a ratio. That observation describes the interval’s relation to equality; it does not, on its own, settle a non-inferiority question, which depends on the prespecified margin and direction of comparison. A p-value for the primary comparison is not reported.

Why does the analysis population matter?

The stated population is the Per Protocol Set. The registry describes it as eligible participants who received the intervention, had pre-dose and post-dose immunogenicity results, complied with blood-draw intervals, and had no intercurrent condition or prohibited concomitant medication that could interfere with immunogenicity. Such restrictions define which participants contribute to the primary estimate. As a general matter, a per-protocol analysis can be sensitive to post-randomization exclusions, so the number and reasons for exclusions and missing assessments are important for evaluating potential bias. Those details are not reported in the registry record.

The study is randomized, but this primary result compares vaccine groups enrolled in different settings and includes only participants in the stated analysis set. Randomization procedures, site distribution, and any adjustment for study or geographic setting beyond the stated model are not reported. Those details would help readers assess how directly the group comparison represents a randomized contrast.

How should multiple outcomes be considered?

The registry lists 20 outcome measures, 16 posted secondary outcomes, and 8 analyses. When many outcomes or comparisons are examined, the chance of observing a nominally notable result by chance can increase. This general issue is called multiplicity. Statistical plans may address it through prespecified hierarchies or adjustments, but multiplicity procedures are not reported in the registry record. No inference should be made that an adjustment was or was not used based only on the number of listed outcomes.

The registry does not report an interim-analysis plan, missing-data method, sensitivity analysis, or sample-size justification. Those items are relevant to understanding how the primary result was planned and how robust it is to assumptions. Their absence from the registry record limits assessment of the analysis beyond the model and population description that are recorded.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s ANCOVA comparison as a group GMT ratio of 1.11, with a 95% confidence interval from 1.04 to 1.20, and labels the analysis non-inferiority. The adjusted group estimates are 5677 for China and 6330 for overseas. These are the posted primary results; a separate recalculated ratio or interval is not reported in the registry record.

No discrepancy is flagged between the sponsor analysis and a recalculation. That status does not supply additional numeric results or details about how any recalculation was conducted. The sponsor’s own analysis is the relevant analysis to report because the registry gives its model, adjusted estimates, and non-inferiority classification. The registry record does not report the non-inferiority margin, its justification, or a p-value, so those elements cannot be independently assessed from the posted comparison alone.

A simple comparison reconstructed from rounded summary statistics would not necessarily reproduce an ANCOVA result. The reported analysis adjusts for pre-dose titers on the log10 scale, while a reconstruction from group summaries would not have the participant-level covariate information or the full model. Any such unadjusted reconstruction would therefore answer a different, more limited question and should not replace the sponsor’s adjusted analysis.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, 16 posted secondary outcomes, and 8 analyses. The primary result concerns RSV-A neutralizing titers at Day 31. Listed secondary outcomes include RSV-A and RSV-B titers at baseline and later visits, seroresponse, comparisons between overseas and China vaccine groups, and respiratory illness outcomes. This breadth makes multiplicity relevant: when many outcomes are assessed, interpreting each result as if it were the only planned test can overstate the strength of evidence. This is a general statistical concern, not a claim that the reported findings are invalid.

The multiplicity strategy is not reported in the registry record. It is therefore not possible to determine from the record whether outcomes were arranged in a testing hierarchy, whether error rates were adjusted, or whether some analyses were considered exploratory. The registry’s list of outcomes and analyses does not itself establish which comparisons were confirmatory.

The primary endpoint population is described as the Per Protocol Set. Participants had to receive intervention, have pre-dose and post-dose results, comply with blood-draw intervals, and meet other stated conditions. The registry does not report the number excluded from this set, the reasons for exclusion, the extent or pattern of missing titers, or the method used to address missing data. It also does not report sensitivity analyses assessing the impact of exclusions or missing observations.

The total enrollment was 2620, while the primary analysis includes 1175 China vaccine participants and 757 overseas vaccine participants. The registry does not explain the relationship between enrollment, randomization, and inclusion in these two analysis groups in sufficient detail to account for all participants. The analysis counts should therefore be read as endpoint-specific counts, not as a complete participant-flow account.

The registry does not report an interim-analysis plan, sample-size justification, or detailed statistical analysis plan. Without those details, readers cannot assess the planned power, stopping rules, prespecified handling of multiplicity, or all assumptions behind the primary analysis. These items are not recoverable from the reported endpoint and model description alone.

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: pneumonia (0.7%), arteriosclerosis coronary artery (0.5%), chronic obstructive pulmonary disease (0.5%), deep vein thrombosis (0.4%), inguinal hernia (0.3%).

The registry reports serious adverse events and other adverse events by group. Among 820 overseas vaccine participants at risk, 28 had a serious adverse event and 2 deaths were recorded. Among 1199 China vaccine participants at risk, 53 had a serious adverse event and 2 deaths were recorded. Among 601 China placebo participants at risk, 39 had a serious adverse event and no deaths were recorded. These are group counts in the registry record; they do not by themselves establish that an event was caused by the intervention.

The registry lists the most frequent serious adverse event terms with percentages: pneumonia, 0.7%; coronary artery arteriosclerosis, 0.5%; chronic obstructive pulmonary disease, 0.5%; deep vein thrombosis, 0.4%; inguinal hernia, 0.3%; and cerebral infarction, 0.3%. The record does not specify in this summary which group or groups contributed each term, nor does it provide event-level timing or causal assessments.

Safety counts need to be interpreted in light of group size, follow-up, and how events were defined and collected. Follow-up for China groups could extend to the last acute respiratory illness visit or contact if later than Month 6, whereas overseas participants were followed through Month 6. The registry does not report detailed exposure-adjusted comparisons, statistical uncertainty for these counts, or attribution of the events. They should be read as descriptive safety reporting, not as a causal comparison or a treatment recommendation.

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

The primary result shows that the registry’s adjusted RSV-A antibody-titer estimates at Day 31 were 5677 for China vaccine participants and 6330 for overseas vaccine participants. The sponsor’s ANCOVA analysis reports a group GMT ratio of 1.11, with a 95% confidence interval from 1.04 to 1.20, and classifies the comparison as non-inferiority. The result is evidence about a laboratory immunogenicity measure in the analyzed participants under the stated model.

It does not, on its own, show the magnitude of protection against RSV-associated illness in either group. Antibody titers are not illness events, and the primary endpoint is not a clinical efficacy endpoint. The registry’s brief summary refers to vaccine efficacy demonstrated in a separate global efficacy study, but that study’s results are not the subject of this primary comparison. The current record also states that respiratory illness surveillance was not conducted for overseas participants, limiting direct interpretation of illness occurrence across all groups.

The result does not establish how long the measured response persists beyond the assessments listed, nor does a Day 31 comparison describe every later immune response. It also does not establish an individual participant’s immune response from a group-level adjusted estimate. The confidence interval communicates statistical uncertainty about the group ratio under the analysis model; it does not eliminate uncertainty about study design, measurement, missing observations, or generalizability.

The registry’s non-inferiority classification should be understood alongside the unavailable margin and decision rule. Without them, the reader cannot independently verify what degree of difference was considered acceptable. The reported estimate and interval remain interpretable as the sponsor’s posted comparison, but they do not support claims beyond that comparison. In particular, they do not establish superiority, equivalence, or a particular clinical benefit, and they are not a basis for medical advice.

More complete interpretation would depend on the full protocol and analysis plan, the rationale for the non-inferiority margin, participant disposition, missing-data handling, and the results for other prespecified endpoints. Those details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a consequential statistical issue in immuno-bridging: the primary comparison is between vaccine recipients in China and overseas, with antibody response summarized at a specified post-vaccination time. Such comparisons rely on a clear definition of the target populations, comparable measurement, and a prespecified standard for judging whether the observed difference is acceptable. The registry describes an adjusted analysis and labels it non-inferiority, but the margin and its justification are not reported. That omission limits independent evaluation of the central inferential claim.

The endpoint also illustrates why analysis scale matters. Neutralizing titers were analyzed on the log10 scale and expressed as adjusted geometric mean titers, which is a common way to summarize antibody measurements. The resulting ratio is more informative for a relative comparison than comparing raw group summaries alone, but it must be interpreted with its direction, confidence interval, model, and non-inferiority criterion in view.

Another important statistical feature is the distinction between immune response and clinical illness. The primary endpoint assesses RSV-A neutralizing titers, while respiratory illness surveillance was conducted only in China. Those components answer different questions and have different observation coverage. A sound interpretation keeps the laboratory endpoint separate from illness occurrence and does not extend the immune result into an unreported clinical-effect estimate.

Finally, the registry lists a broad set of outcome measures, while providing limited detail about multiplicity, missing data, participant flow, and the analysis plan. These are central to judging the reliability and scope of trial conclusions. The posted primary analysis is useful, but its interpretation is strongest when treated as a model-based result with clearly bounded claims and with the unreported design details kept visible.

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 non-inferiority margin or its justification. Although the primary analysis is labeled non-inferiority, this missing information prevents independent assessment of the formal criterion against which the ratio and confidence interval were judged. The numerator and denominator convention for the ratio is also not explicitly stated in the record.

The primary analysis is restricted to the Per Protocol Set. The record describes eligibility conditions but does not provide a complete participant-flow account, reasons for exclusion, or the number of missing immunogenicity assessments. Missing-data methods and sensitivity analyses are not reported. These omissions limit assessment of whether the analyzed population differs in important ways from participants who were enrolled or randomized.

There is a geographic and study-context component to the comparison: China vaccine participants are compared with overseas vaccine participants, and the brief summary identifies the overseas participants as being drawn from the referenced RSV OA=ADJ-006 study. The registry does not report detailed information on site distribution or other factors that could affect comparability, beyond the stated ANCOVA adjustment for pre-dose log10 titers.

Respiratory illness surveillance was not conducted for overseas participants. Clinical illness outcomes therefore cannot be interpreted as a complete parallel comparison across the China and overseas groups. In addition, safety counts are descriptive in the registry summary; event attribution, timing, and statistical comparisons are not reported there.

Multiplicity procedures, interim analyses, sample-size justification, and the full statistical analysis plan are not reported in the registry record. The protocol details behind the masking descriptions—quadruple masking in the registry and partially blind in the official title—are also not reported. These limitations concern the extent to which the primary analysis and other outcomes can be independently evaluated; they do not change the numeric results that are posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study on the Immune Response, Safety and the Occurrence of Respiratory Syncytial Virus (RSV)-Associated Respiratory Tract Illness After Administration of RSV OA Vaccine in Adults 60 Years and Older — NCT06551181.
• Registry record last updated 2026-11-06; status last verified 2026-10.
• Results first posted 2026-05-19.
• 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

NCT06551181 is a completed Phase 3 randomized, controlled, parallel-group study of RSVPreF3 OA investigational vaccine and placebo in adults aged 60 years and older. The registry reports quadruple masking, while the official title describes the study as partially blind. Enrollment was 2620; the recorded start date was 2024-08-05, and the primary completion date was 2025-04-24.

The primary endpoint was the adjusted RSV-A neutralizing GMT at Day 31, analyzed using ANCOVA on log10 titers with pre-dose log10 titer as a covariate. The China vaccine group’s adjusted GMT was 5677 (95% CI 5419 to 5946), and the overseas vaccine group’s adjusted GMT was 6330 (95% CI 5974 to 6706). The reported group GMT ratio was 1.11 (95% CI 1.04 to 1.20), classified as non-inferiority. The margin, multiplicity procedure, missing-data methods, and fuller participant-flow details are not reported in the registry record.

The study also assessed safety and respiratory illness outcomes. Acute respiratory illness surveillance was limited to China participants. Safety counts are descriptive and do not establish event causality.