A Study to Evaluate the Safety and Immunogenicity for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Immunogenicity for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older (NCT03502707), a randomized phase 1, phase 2 study. The primary outcome is Cohort 1: Number of Participants With Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled Phase 1/2a study with a parallel-group design and quadruple masking. The registry lists enrollment of 669 and a healthy population aged 60 years and older. The study started on 2018-07-06, had primary completion on 2022-05-16, and is listed as completed. Janssen Vaccines & Prevention B.V. is named as sponsor.

The study was organized into three cohorts. Cohorts 1 and 2 were used to assess safety and reactogenicity across one-dose and two-dose regimens; Cohort 1 also included a booster at Month 12. The stated aim was to select a regimen for Cohort 3. Cohort 2 and part of Cohort 1 were also used to compare RSV neutralizing antibody levels for regimens containing RSV pre-fusion protein with a one-dose Ad26.RSV.preF regimen. Cohort 3 assessed the selected regimen and booster administration at Month 12 and/or Month 24.

The interventions included placebo, RSV preF Protein 50 mcg, RSV preF Protein 150 mcg, Ad26.RSV.preF 1*10^11 vp, and mixtures combining Ad26.RSV.preF with RSV preF protein at specified doses. Some groups received components as separate injections. Regimens and dosing schedules varied by cohort and group, so the arms should not be treated as though they differed only in one feature. Cohort 1 included several small groups; the primary outcome lists 8 participants in each active group and 16 in pooled placebo. Cohort 2 and Cohort 3 had additional groups and schedules.

The registry record does not report the rationale for the total enrollment or the allocation ratio within every cohort. It also does not report a detailed protocol for regimen selection beyond the stated study aims and group descriptions.

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.

Only the first 6 of 18 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set (FAS) included all participants who were randomized and received at least one dose of vaccine (active or placebo), regardless of the occurrence of protocol deviations or the type of vaccine.

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.

Population: The full analysis set (FAS) included all participants who were randomized and received at least one dose of vaccine (active or placebo), regardless of the occurrence of protocol deviations or the type of vaccine.

Only the first 6 of 19 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Cohort 1: Number of Participants With Serious Adverse Events (SAEs), measured over From Day 1 up to Day 730.

The primary endpoint is the number of Cohort 1 participants with serious adverse events (SAEs) from Day 1 up to Day 730. The registry defines an adverse event as an untoward medical occurrence that does not necessarily have a causal relationship with the study agent. An SAE is an event resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, a congenital anomaly or birth defect, suspected transmission of an infectious agent through a medicinal product, or another medically important event.

Counting participants with at least one SAE is a safety measure. It gives a direct count of people who met the registry’s seriousness criteria over the stated follow-up window. It is not a measure of all symptoms or all adverse events: non-serious events are outside this primary endpoint, even though the registry separately lists counts for other adverse events. Nor does the endpoint establish whether an event was caused by vaccination. The registry definition explicitly allows events without a causal relationship to the study agent.

The primary outcome was planned for specified arms only, and the listed analysis population was the full analysis set: randomized participants who received at least one dose, regardless of protocol deviations or vaccine type. The registry record does not report a formal hypothesis test, adjusted estimate, or confidence interval for this endpoint. Thus, the posted counts describe the safety outcome in the listed arms, but they do not provide a reported inferential comparison between regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpretation depends first on the outcome’s scale. This is a binary participant-level outcome: each participant either met the SAE definition during the specified follow-up or did not. The reported result is a count of participants with an event, alongside the number of participants at risk. Unlike a continuous measure such as an antibody titer, this endpoint does not describe the size of an individual response. It also does not count the total number of SAE episodes; it counts participants with SAEs.

What does a confidence interval express?

General statistical explanation: a confidence interval is a range of values compatible with the observed data under a specified statistical procedure. It communicates uncertainty in an estimate; a wider interval generally indicates less precision. For a comparison of binary outcomes, an interval might describe uncertainty around a difference or ratio between groups. No confidence interval or comparative estimate for the primary endpoint is reported in the registry record, so the precision of a between-group effect cannot be read from the posted SAE counts alone.

Why do small groups require caution?

General statistical explanation: estimates from small groups can vary substantially from one sample to another. A small number of events or no observed events does not rule out a nonzero underlying event probability. That issue matters for the Cohort 1 groups, which list 8 participants per active group and 16 participants in pooled placebo. The observed counts are still useful as descriptions of what was recorded, but they are not highly precise comparative estimates. No confidence intervals are posted to quantify that uncertainty.

Why distinguish description from inference?

Descriptive statistics report what was observed in the analyzed participants. Inferential statistics use a model or test to estimate uncertainty and assess a contrast beyond the sample. Here, the registry record posts participant counts but lists zero analyses. It does not report a statistical test, a model-based estimate, a prespecified contrast, or a p-value for the primary endpoint. Consequently, the counts can be read arm by arm, but they cannot establish a statistically supported difference between arms.

General statistical explanation: a randomized design can help balance measured and unmeasured participant characteristics across groups on average, but randomization does not eliminate chance imbalances, particularly in small groups. Masking can reduce some forms of bias during treatment and assessment, but the registry’s design labels alone do not demonstrate how well masking was maintained. The record does not report details on these matters.

What does the planning illustration mean?

The sample-size section is described as a planning illustration based on the observed effect, not the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration reports participants per arm for a specified power; time-to-event illustrations use a total event count. Such calculations are prospective planning aids, not observed power and not evidence that the study was designed to detect a particular effect. The registry record does not report the trial’s own sample-size justification. The numerical planning results are not included in the record details summarized for this analysis.

General statistical explanation: when a binary outcome is uncommon, different methods can behave differently, especially with small groups or zero-event arms. Some approaches rely on large-sample approximations; others use exact or model-based procedures. The registry record does not report which method, if any, was used for a comparison of the primary endpoint. No method should be attributed to the sponsor beyond what the record explicitly states.

How should event timing and attribution be read?

The endpoint covers SAEs over a follow-up window from Day 1 up to Day 730. A participant-level count over a fixed window does not show when an event occurred, how long it lasted, or whether several episodes happened to the same participant. The endpoint definition also makes clear that a serious event need not be causally related to the study agent. The registry does not provide causal assessments for the listed primary-outcome counts, so temporal occurrence during follow-up should not be mistaken for evidence of causation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1: Pooled Placebo", "Cohort 1: RSV preF Protein 50 mcg", "Cohort 1: Ad26.RSV.preF 5*10^10 vp + RSV preF Prot", "Cohort 1: RSV preF Protein 150 mcg", "Cohort 1: Ad26.RSV.preF 5*10^10 vp + RSV preF Prot", "Cohort 1: Ad26.RSV.preF 1*10^11 vp + RSV preF Prot")
n      <- c(16, 8, 8, 8, 8, 8)
events <- c(3, 0, 0, 2, 3, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1: Pooled Placebo  16  3  18.8  4.0  45.6  6.6  43.0  6.8  43.4
ARM  Cohort 1: RSV preF Protein 50 mcg  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  Cohort 1: Ad26.RSV.preF 5*10^10 vp + RSV preF Prot  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  Cohort 1: RSV preF Protein 150 mcg  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0
ARM  Cohort 1: Ad26.RSV.preF 5*10^10 vp + RSV preF Prot  8  3  37.5  8.5  75.5  13.7  69.4  13.7  70.1
ARM  Cohort 1: Ad26.RSV.preF 1*10^11 vp + RSV preF Prot  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The study had multiple cohorts, many vaccine regimens, and outcomes spanning safety and immunogenicity. The registry lists 33 outcome measures, while 12 secondary outcomes are posted. When many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can rise unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory comparisons, or which secondary outcomes were intended as confirmatory rather than exploratory. It is therefore not possible to interpret the posted outcome set as a single family of controlled hypothesis tests.

The record lists zero analyses for the primary endpoint. It does not report an inferential comparison, a statistical analysis plan, a missing-data method, or handling rules for participants who did not complete follow-up. The primary outcome population is defined as the full analysis set, consisting of randomized participants who received at least one dose. That definition identifies the population intended for analysis but does not by itself explain how missing outcome status, incomplete follow-up, or protocol deviations were handled.

Interim analyses and stopping rules are not reported in the registry record. A detailed sample-size justification is also not reported in the registry record. These omissions mean that the available record does not establish whether any planned multiplicity control, missing-data strategy, interim monitoring, or analysis decisions were specified elsewhere in the protocol. The posted counts should therefore be treated as descriptive information rather than as results from a documented confirmatory testing strategy.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: melaena (12.5%), diverticulitis (12.5%), back pain (12.5%), bladder cancer (12.5%), lacunar infarction (12.5%).

The primary safety outcome counts participants with at least one SAE in Cohort 1 during follow-up from Day 1 up to Day 730. Pooled placebo reports 3 of 16 participants. Among the listed active groups, the counts range from 0 of 8 to 3 of 8. The record separately reports deaths and other adverse events for broader groups across Cohorts 1, 2 and 3. Those measures should not be conflated: the primary endpoint is an SAE participant count, whereas the separate other-adverse-event counts cover a different category.

The cohort-wide safety listing includes 14 of 135 SAEs in the Cohort 3 mixture group, 16 of 136 in the Cohort 3 mixture-and-placebo group, and 3 of 44 in Cohort 3 pooled placebo. The listed deaths are reported separately; the registry record does not provide a basis for attributing them to a study regimen. It also lists serious-event terms including Melaena, Diverticulitis, Back Pain, Bladder Cancer, Lacunar Infarction and Aortic Aneurysm, each shown as 12.5%. These terms do not establish causation or comparative risk.

Counts across cohorts should not be combined or treated as directly comparable without a defined analysis. Small groups, different schedules, and the absence of a reported adjusted comparison limit interpretation. These are records of events during study follow-up, not proof that a regimen caused or prevented an event.

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

The posted results describe serious adverse events recorded among participants assigned to specified study groups. They show that events were recorded in pooled placebo and in some active groups, while several active groups had no participant recorded with an SAE for the primary outcome. The observed counts are relevant descriptive safety information for this study’s population and follow-up period.

They do not establish a causal relationship between a vaccine regimen and an SAE. The endpoint definition explicitly includes events that may not be related to the study agent, and the listed counts do not provide adjudication or causal assessments. They also do not establish that an arm with no observed events has no underlying risk. The group sizes in Cohort 1 are small, and the registry record does not report confidence intervals or an inferential comparison to quantify uncertainty.

The endpoint does not answer whether a regimen generated an immune response. Antibody neutralization and F-protein antibody titers were among the secondary outcomes, but those are distinct measures from SAE counts. Nor do the safety counts establish protection against RSV illness: the primary endpoint is not a clinical efficacy endpoint, and no RSV disease outcome is specified as the primary measure in the record details.

The trial had regimen-selection aims, but the posted primary endpoint alone cannot identify a preferred regimen. The record describes selection as an aim and gives details of selected-regimen evaluation in Cohort 3, yet it does not report a formal primary safety comparison or a complete account of the selection decision. A defensible reading stays close to the data: the listed numbers are participant counts in the specified groups over the stated period, with substantial limits on causal and comparative interpretation.

14. Why This Trial Matters Statistically

This study illustrates why early-phase and regimen-selection trials often need to be read across several dimensions. The interventions varied in composition, dose, delivery as a mixture or separate injections, and schedule. A group-level contrast can therefore reflect more than one treatment feature unless the intended comparison is clearly specified. Randomization and masking are important design features, but they do not make every group comparison equivalent or remove the need to understand the cohort and regimen structure.

It also illustrates the distinction between a safety count and a comparative estimate. Reporting how many participants had SAEs is valuable for describing observed events. To assess the size and precision of a difference between regimens, readers would also need a defined contrast and uncertainty measure. The registry’s primary endpoint has counts, but no analyses are listed. This makes it especially important not to turn apparent differences between small groups into claims of superiority or harm.

Finally, a study can have several objectives that rely on different outcomes. Safety and reactogenicity, regimen selection, and antibody responses are not interchangeable questions. A safety endpoint can inform the safety description without answering an immunogenicity question, and antibody measurements do not substitute for clinical disease outcomes. Keeping each endpoint tied to its purpose helps prevent claims from extending beyond what the posted data can support.

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 primary endpoint results cover Cohort 1 and only specified arms. They do not provide a complete safety comparison across every intervention in the trial. The primary outcome groups are small, and the record does not report confidence intervals, adjusted estimates, or tests of between-group differences. As a result, precision and comparative uncertainty cannot be assessed from the primary counts alone.

The study’s cohorts had different regimens and dosing schedules. The registry descriptions also note pooled data for some groups across cohorts. Without a reported analysis plan or detailed explanation of pooling, those data should not be assumed to form directly comparable groups. The endpoint is a participant count over a long follow-up window; the registry entries do not describe event timing, recurrent events per participant, severity beyond the SAE definition, or causal adjudication.

The registry record does not report the trial’s sample-size justification, detailed statistical plan, interim analyses, missing-data methods, or multiplicity strategy. These gaps limit assessment of design choices and the intended strength of evidence. Although enrollment is listed as 669, that total should not be mistaken for the number contributing to the Cohort 1 primary outcome. The analysis population is defined, but the record details do not state a total analyzed for that endpoint.

The study’s stated aims include antibody responses, but numerical secondary outcome results are not included in the record details. Therefore, this account cannot characterize the immunogenicity findings or connect them with the SAE counts. No inference about clinical RSV protection follows from the primary safety endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Immunogenicity for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older — NCT03502707.
• Registry record last updated 2025-05-25; status last verified 2025-05.
• Results first posted 2023-09-13.
• 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.

19. Record Summary

NCT03502707 is a completed randomized, double-blind, placebo-controlled Phase 1/2a parallel study sponsored by Janssen Vaccines & Prevention B.V. It enrolled 669 healthy adults aged 60 years and older and evaluated Ad26.RSV.preF, RSV preF protein, combinations, and placebo across three cohorts. The primary endpoint counted Cohort 1 participants with SAEs from Day 1 up to Day 730. The posted Cohort 1 counts range from 0 of 8 to 3 of 8 in active groups, with 3 of 16 in pooled placebo. No analyses are listed for the primary endpoint. The counts are descriptive and do not establish causation or a comparative treatment effect. The registry also lists secondary antibody outcomes and broader safety counts, but the record does not report the statistical plan, missing-data procedures, multiplicity handling, or interim analyses.