A Study in India on the Immune Response and Safety of a Respiratory Syncytial Virus (RSV) Older Adults (OA) Vaccine When Given to Older Adults 60 Years of Age and Above and Adults 50-59 Years of Age at Increased Risk (AIR) of Respiratory Syncytial Virus Lower Respiratory Tract Disease (RSV-LRTD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in India on the Immune Response and Safety of a Respiratory Syncytial Virus (RSV) Older Adults (OA) Vaccine When Given to Older Adults 60 Years of Age and Above and Adults 50-59 Years of Age at Increased Risk (AIR) of Respiratory Syncytial Virus Lower Respiratory Tract Disease (RSV-LRTD) (NCT06614725), a randomized phase 3 study. The primary outcome is RSV-A Neutralizing Titers Expressed as Geometric Mean Titers (GMTs).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, placebo-controlled, parallel-group study conducted in India. The registry record describes masking as quadruple; the official title describes the study as observer-blind. These are the masking descriptions recorded for the study, and the record does not detail which roles were masked or how masking was maintained.

The four groups were defined by population and assigned intervention: older adults at least 60 years of age received vaccine or placebo, and adults 50-59 years of age at increased risk of RSV-LRTD received vaccine or placebo. The intervention was a single dose given on Day 1. The registry record reports enrollment of 751, a start date of 2024-10-01, primary completion on 2025-06-03, and study status as completed.

The stated purpose was to evaluate immunogenicity and safety. The primary endpoint listed in the results is RSV-A neutralizing titers measured at Day 1 before intervention administration. The listed primary analysis population is the per protocol set for RSV-A. The registry record describes eligible participants who received intervention as per protocol and had pre- and post-dose immunogenicity results, with further criteria involving blood-draw intervals and prohibited concomitant medication or vaccination. The available population description ends before the complete eligibility criteria are stated.

The posted secondary outcomes include solicited administration-site events, solicited systemic events, unsolicited adverse events, serious adverse events, and potential immune-mediated diseases. The record lists 9 outcome measures and reports no analyses in its analysis count. It does not report a detailed design rationale or a statistical analysis plan.

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: Out of 751 participants enrolled, 750 received the study intervention (RSVPreF3 OA investigational vaccine or placebo) and were included in the Exposed Set.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the per protocol set(PPS) for RSV-A which included all eligible participants who received the study intervention as per protocol,had RSV-A immunogenicity results pre- and post-dose, complied with blood draw intervals, without prohibited concomitant medication/vaccination and intercurrent conditions that may interfere with immunogenicity.Only participants included in pre-vaccination timepoint and with data available for RSV-A titers at Day1 were included in the analysis.

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 Geometric Mean Titers (GMTs), measured over At Day 1 (pre-study intervention administration).

The primary endpoint is RSV-A neutralizing antibody titer, expressed as a geometric mean titer (GMT) in estimated dilution 60 (ED60). Neutralizing titers measure the level of antibody activity against RSV-A in the blood sample. A GMT summarizes titers on a multiplicative scale, which is commonly used for antibody measurements that can vary across a wide range. This is a general explanation of the measure.

The reported timeframe is Day 1 before study intervention administration. The endpoint therefore describes baseline antibody levels in the per protocol analysis set; it is not a post-dose response measurement. The group GMTs and their 95% confidence intervals give a summary of the baseline titers and their statistical precision.

Immune-response studies commonly assess antibody measures to characterize the immune response to a vaccine. For that purpose, post-dose measurements or changes from baseline are needed to describe response after administration. Those post-dose results are not included in the primary endpoint reported in the registry record. The primary result should consequently be read as a baseline description, not as evidence of a vaccine-induced increase or a comparison of immune response between assigned groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean summarize?

A GMT summarizes measurements that are analyzed on a logarithmic scale and then expressed back on the original scale. This is a general statistical approach often used for antibody titers because titers can vary multiplicatively. The GMT is not the same as an ordinary arithmetic average. It represents a central summary that is less influenced by the scale’s multiplicative spread than an arithmetic mean might be. In this study, the unit is ED60, and the endpoint is described as RSV-A neutralizing titers.

The registry record reports one GMT for each of the four groups. These summaries should be interpreted within their respective populations: older adults at least 60 years of age, and adults 50-59 years of age at increased risk of RSV-LRTD. The two population groups differ by age and risk definition, so their summaries are not a randomized comparison with each other. The intervention comparisons of interest would be vaccine versus placebo within each population, but the posted primary endpoint is timed before intervention administration.

What does a 95% confidence interval communicate?

A confidence interval describes statistical uncertainty around an estimate, under the assumptions of the method used. In repeated applications of a method with its assumptions satisfied, intervals constructed in this way would capture the underlying parameter at the stated rate. It is not a range that guarantees the true value is contained in any one interval, nor does it describe the range of individual participants’ measurements. The primary result gives a separate interval for each group GMT.

Comparing intervals by eye is not the same as testing a contrast between groups. Overlapping intervals do not prove equality; non-overlap is not the only route to a statistical difference. A formal comparison requires an estimate of the contrast and its uncertainty, calculated with a method appropriate to the analysis. The registry record does not report such a primary contrast for the baseline titers. The confidence intervals therefore support interpretation of the precision of each group summary, not a treatment-effect claim.

Why does timing matter?

For a randomized intervention study, the timing of an outcome determines what question it can address. A measurement collected before intervention administration describes the participants at baseline. It cannot represent a response caused by an intervention that has not yet been given. A post-dose measurement, a change-from-baseline analysis, or another prespecified response measure would be needed to assess immune response after dosing. The primary endpoint recorded for this study is explicitly at Day 1 before administration. Although the study purpose refers to immunogenicity, the posted primary result does not provide the post-dose evidence needed to characterize that response.

How should the analysis population be read?

The primary result is reported for the per protocol set for RSV-A. In general, a per protocol population includes participants who satisfy specified study and measurement requirements. The record says this set included eligible participants who received study intervention as per protocol, had pre- and post-dose RSV-A immunogenicity results, and complied with blood-draw intervals, with restrictions involving prohibited concomitant medication or vaccination. The recorded description is incomplete, so the full set of eligibility and exclusion rules is not reported in the registry record.

A per protocol summary can differ from an analysis of all randomized participants because inclusion depends on meeting protocol criteria and having required measurements. The registry record does not describe missing-data methods, imputation, or a separate intention-to-treat analysis for this endpoint. As a result, the influence of missing measurements or post-randomization exclusions cannot be assessed from the posted description.

How should the secondary comparisons and planning illustrations be understood?

The unsolicited adverse-event comparisons are reported with unadjusted p-values. A p-value summarizes how compatible the observed data are with a specified null hypothesis under the assumptions of the test; it does not measure the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Unadjusted means the reported value has not been adjusted for testing multiple outcomes or comparisons. The registry record does not report a multiplicity strategy or a broader analysis plan.

Sample-size illustrations based on observed effects are planning exercises, not results from this completed trial and not observed power. The record describes those illustrations as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with planning effects set as fractions of the observed effect. These assumptions describe the illustration, not the trial’s original design. The illustrations cannot establish that the trial was adequately powered for its original objectives. The sample-size justification and the assumptions used for the trial’s actual design are not reported in the registry record.

Over-dispersion is a general issue when count data vary more than a model’s assumed distribution allows. 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 a count-model analysis or information allowing over-dispersion to be assessed; this concept should not be taken as a description of a method used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcome measures, including the primary RSV-A GMT and secondary measures covering solicited and unsolicited events, serious adverse events, and potential immune-mediated diseases. It reports no analyses in its analysis count. A multiplicity plan describing which outcomes or comparisons were confirmatory, how error across tests would be controlled, or which results were exploratory is not reported in the registry record.

The detailed unsolicited adverse-event comparisons are accompanied by unadjusted p-values. Those values do not account for the fact that more than one comparison or outcome may be examined. Without a prespecified hierarchy or adjustment method, nominal p-values should not be treated as if they provide confirmatory evidence across the collection of outcomes. The statistical analysis plan, including any interim analyses or prespecified testing sequence, is not reported in the registry record.

Missing-data handling is also not reported. The primary analysis is described as using the per protocol set for RSV-A, with requirements that include pre- and post-dose immunogenicity results and compliance with blood-draw intervals. The record does not give the complete population definition, numbers excluded for each reason, methods for handling missing titers, or sensitivity analyses. It also does not report a separate analysis population intended to include all randomized participants.

These omissions limit assessment of whether exclusions or missing measurements could affect the estimates. They also make it difficult to connect the posted summaries to an analysis plan established before results were known. The sample-size justification for the trial is not reported in the registry record. Planning illustrations calculated from observed effects are not evidence of the original design’s power or adequacy.

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: covid-19 (0.4%), chronic obstructive pulmonary disease (0.4%).

The registry safety summary reports serious adverse events in the four groups as follows: 0 of 260 in the OA-RSV Group, 0 of 130 in the OA-Placebo Group, 1 of 240 in the Adults-AIR-RSV Group, and 0 of 120 in the Adults-AIR-Placebo Group. Deaths are reported as 0 in each group. COVID-19 and chronic obstructive pulmonary disease are each listed among the top serious-event terms at 0.4%.

These are event counts recorded in the registry, not evidence by themselves that an event was caused by the assigned intervention. A zero count means no event was recorded in that group under the study’s reporting and follow-up procedures; it does not establish that an event is impossible or that risk is absent. The registry record does not give the serious-event follow-up timeframe, event-level narratives, or a causal assessment for the recorded serious event.

The group counts should be read in their separate age-and-risk populations. They do not support a pooled safety estimate, and no such estimate is calculated. The record also lists secondary outcomes for solicited events and potential immune-mediated diseases, but complete results for those outcomes are not reported in the registry record.

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

The primary result establishes that the registry record contains baseline RSV-A neutralizing antibody GMTs for the per protocol analysis population in each of four study groups. It also provides 95% confidence intervals that convey uncertainty around those group summaries. This is useful descriptive information about the measured titers before study intervention administration.

It does not establish how antibody titers changed after vaccination. It does not show that vaccine and placebo produced different post-dose immune responses, because the reported primary measurement was collected before either was administered. It also does not establish an effect on RSV-LRTD or prevention of RSV infection; those clinical outcomes are not reported as results in the registry record.

The randomized design is relevant to comparisons of assigned interventions, but interpretation still depends on having a suitable outcome measured after assignment and on a prespecified analysis. For the primary endpoint posted, the timing is not suitable for estimating a post-intervention effect. A baseline difference between groups, whether in one direction or another, is not a vaccine response.

Safety counts provide a separate, limited description of recorded adverse events. The serious-event figures are small counts over an unspecified serious-event follow-up period, and the record does not report causal assessments. They should not be read as a complete characterization of safety or as proof that risks are absent.

In short, the posted results support a baseline antibody description and a limited account of reported adverse events. They do not answer the study’s broader immunogenicity objective with a post-dose comparison, and they do not support conclusions about clinical protection. Missing details on analyses, populations, and outcome reporting further limit how far the posted findings can be interpreted.

13. Why This Trial Matters Statistically

This trial illustrates why the timing attached to an endpoint is as important as the endpoint’s name. A neutralizing antibody GMT sounds like an immune-response measure, and the stated study purpose concerns immunogenicity, but the primary result is explicitly measured before intervention administration. That distinction determines what the results can support: a baseline description rather than an intervention response.

The four-group structure also matters for statistical interpretation. Results are separated by older-adult status and increased-risk adult status, with vaccine and placebo groups in each population. Keeping these populations distinct avoids treating groups with different eligibility definitions as if they were one uniform comparison. It also means that each within-population intervention question requires its own appropriately timed estimate and analysis.

The record offers another useful lesson about evidence strength. Confidence intervals around group summaries help readers assess precision, but they are not a substitute for a direct comparison. Unadjusted secondary p-values, especially when several outcomes are listed and no multiplicity plan is reported, should be interpreted cautiously. Planning illustrations derived from observed effects likewise do not establish what the original study was designed to detect.

Finally, registry reporting is part of statistical transparency. The incomplete per protocol description, absent missing-data methods, and lack of a reported analysis plan restrict assessment of selection, multiplicity, and robustness. These limits do not erase the descriptive information that is posted, but they define the questions that the registry record can and cannot answer.

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 principal endpoint-specific limitation is that RSV-A GMT was measured at Day 1 before study intervention administration. Although the study purpose refers to immune response, the primary result reported does not quantify a post-dose response. Post-dose group summaries, change-from-baseline estimates, and a primary vaccine-versus-placebo comparison are not reported in the registry record.

The analysis population is the per protocol set for RSV-A, and the registry description of its criteria is incomplete. The record does not report the full participant flow into that set, reasons for exclusion, missing-data methods, or sensitivity analyses. It is therefore not possible to assess from the registry record how much the per protocol requirements or unavailable measurements may have influenced the results.

Several secondary outcomes are listed, but complete results are not reported for all of them. Detailed unsolicited adverse-event comparisons are available, while the broader secondary pattern cannot be fully evaluated. Serious-event follow-up timing and causal assessments are not reported. These gaps constrain interpretation of the safety information.

The registry record reports no analyses in its analysis count and does not provide the statistical analysis plan, multiplicity strategy, interim-analysis details, or original sample-size justification. Its planning illustrations use observed effects and should not be mistaken for the trial’s design assumptions or observed power. The study was conducted in India and enrolled the specified age-and-risk groups; the record alone does not establish how well findings would apply to other populations or settings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in India on the Immune Response and Safety of a Respiratory Syncytial Virus (RSV) Older Adults (OA) Vaccine When Given to Older Adults 60 Years of Age and Above and Adults 50-59 Years of Age at Increased Risk (AIR) of Respiratory Syncytial Virus Lower Respiratory Tract Disease (RSV-LRTD) — NCT06614725.
• Registry record last updated 2026-06-23; status last verified 2026-05.
• Results first posted 2026-06-23.
• 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

NCT06614725 is a completed Phase 3, randomized, placebo-controlled, parallel-group study conducted in India. It enrolled 751 participants and evaluated a single dose of RSVPreF3 OA investigational vaccine in older adults at least 60 years of age and adults 50-59 years of age at increased risk of RSV-LRTD.

The primary result is RSV-A neutralizing antibody GMT at Day 1 before intervention administration, analyzed in the per protocol set for RSV-A. It describes baseline titers rather than a post-dose response. The registry record also lists secondary reactogenicity and safety outcomes and reports limited adverse-event information, including serious-event counts and unsolicited adverse-event comparisons.

Post-dose primary immune-response comparisons, a complete statistical analysis plan, full missing-data methods, and complete results for all listed secondary outcomes are not reported in the registry record. These gaps limit conclusions about intervention effects and the overall pattern of outcomes.