This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Evaluate the Immune Response After a Booster Dose of a Quadrivalent Meningococcal (MenACYW) Conjugate Vaccine When Administered Alone or Concomitantly With a Licensed Meningococcal Serogroup B Vaccine, in Participants Who Received Primary Quadrivalent Meningococcal Conjugate Vaccine (MCV4) (NCT04084769), a randomized phase 3 study. The primary outcome is Percentage of Participants With Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine in Study MET59: Group 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04084769 |
| Phase | Phase 3 |
| Condition | Meningococcal Immunisation (Healthy Volunteers) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 570 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi Pasteur, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents and adults who had received a single dose of a quadrivalent meningococcal conjugate vaccine before entering this study. Some participants had previously received MenACYW and others Menveo; the record describes these earlier vaccinations as occurring 3-6 years before the booster.
Intervention
A single intramuscular dose of MenACYW conjugate vaccine. In two groups it was given alone; in two other groups it was administered concomitantly with a meningococcal group B vaccine, either Trumenba or Bexsero.
Comparator
The primary endpoint is specified for Group 1, which received MenACYW alone after prior MenACYW vaccination. The record does not identify a comparator for that primary endpoint. Other study groups allow description of responses in participants with different prior vaccination or concomitant vaccination.
Primary question
In Group 1, did the percentage of participants with an hSBA seroresponse to meningococcal serogroups A, C, Y, and W meet the registry’s prespecified sufficiency criterion at Day 30 after the booster? The criterion concerns the lower limit of a one-sided 97.5% confidence interval, not simply whether the observed percentage exceeds a threshold.
The clinical question is about antibody response after a booster, rather than a direct comparison of clinical illness outcomes. The endpoint uses a laboratory assay, the serum bactericidal assay using human complement (hSBA), to measure antibody titers against four meningococcal serogroups. Seroresponse is defined according to the participant’s pre-vaccination titer: a qualifying post-vaccination titer is used for participants starting below the stated level, while a four-fold increase is used for participants starting at or above it.
The study also describes secondary immune-response measures. These include seroprotection and geometric mean titers, with measurements before vaccination and at Day 30, and an early measurement at 6 days (±1 day) in a subset of 50 participants per group. The registry record does not report results for these measures in the material available for this analysis. Thus, the design and endpoint definitions clarify what the study set out to assess, but the clinical question cannot be answered from the posted results summarized in the registry record.
3. Trial Design
This was a randomized, open-label, parallel-group Phase 3 study with a registry enrollment of 570. It is listed as completed. The study evaluated a booster dose of MenACYW in participants who had previously received a quadrivalent meningococcal conjugate vaccine. The official title identifies adolescents and adults as the study population, and the listed condition is meningococcal immunisation in healthy volunteers.
Four groups are described. Group 1 received MenACYW alone after prior vaccination with MenACYW in earlier studies. Group 2 received MenACYW alone after prior vaccination with Menveo, either in an earlier study or outside Sanofi Pasteur trials. Group 3 received MenACYW concomitantly with Trumenba, and Group 4 received MenACYW concomitantly with Bexsero. The record describes the booster as a single intramuscular dose at Day 0. Randomization is reported, but the allocation procedure and the allocation ratio are not reported in the registry record.
Masking is listed as none, so the trial was open-label. The parallel model means participants were assigned to a study group rather than described as crossing between interventions. The registry record does not report details of any concealment procedures or explain whether laboratory outcome assessment was masked.
The primary endpoint is focused on Group 1 at Day 30 and measures seroresponse to serogroups A, C, Y, and W. The brief summary also describes a primary objective concerning sufficiency in Groups 1 and 2, but the primary outcome title identifies Group 1. The registry record does not report a primary outcome estimate in the information, and it does not give a primary-endpoint comparison between groups. Therefore, the four-arm design should not be read as evidence that each arm was intended for a direct statistical comparison on the primary endpoint.
Secondary assessments include seroresponse, seroprotection, and geometric mean titers. The record describes Day 0 and Day 30 measurements for Groups 1 and 2, along with an early post-vaccination assessment in a subset. The exact follow-up completeness and the number of participants contributing to each endpoint are not reported in the registry record. The enrollment figure is a study-level figure and should not be treated as the denominator for every analysis.
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: A total of 570 participants who received meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine or Menveo (meningococcal Group B) vaccine either in Study MET50 (NCT02199691), or Study MET43 (NCT02842853), or outside of Sanofi Pasteur trials were enrolled in the present study (MET59).
Overall Study
| Stage | Group 1: MenACYW Conjugate Vaccine | Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine |
|---|---|---|---|---|
| STARTED | 191 | 190 | 95 | 94 |
| Safety Analysis Set (SAfAS) | 186 | 184 | 93 | 92 |
| Full Analysis Set | 191 | 190 | 95 | 94 |
| Per-Protocol Analysis Set 1 (PPAS1) | 46 | 45 | 0 | 0 |
| Per-Protocol Analysis Set 2 (PPAS2) | 174 | 176 | 90 | 89 |
| COMPLETED | 187 | 186 | 95 | 92 |
| NOT COMPLETED | 4 | 4 | 0 | 2 |
Reasons for not completing this period:
| Reason | Group 1: MenACYW Conjugate Vaccine | Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine |
|---|---|---|---|---|
| Protocol Violation | 1 | 3 | 0 | 1 |
| Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Withdrawal by parent/guardian | 1 | 0 | 0 | 1 |
| Lost to Follow-up | 2 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on Per-Protocol Analysis Set 2 (PPAS2) population that included participants who received 1 dose of study vaccine in MET59 and had a valid post-vaccination serology result with no relevant protocol deviation; defined for evaluating the immune response of MenACYW vaccine measured by hSBA or rSBA assessed at Day 30 after vaccination. For this outcome measure, data were not planned to be collected and analyzed for Groups 3, and 4 as pre-specified in the protocol.
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: Analysis was performed on all enrolled participants.
| Characteristic | Unit | Group 1: MenACYW Conjugate Vaccine | Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 191 | 190 | 95 | 94 | 570 | |
| Age, Continuous | years | 15.4 (SD 1.59) | 15.8 (SD 1.37) | 15.1 (SD 1.12) | 15.3 (SD 1.34) | 15.4 (SD 1.43) |
| Sex: Female, Male: Female | Participants | 99 | 85 | 41 | 45 | 270 |
| Sex: Female, Male: Male | Participants | 92 | 105 | 54 | 49 | 300 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 1 | 2 |
| Race (NIH/OMB): Black or African American | Participants | 19 | 16 | 7 | 7 | 49 |
| Race (NIH/OMB): White | Participants | 163 | 165 | 83 | 86 | 497 |
| Race (NIH/OMB): More than one race | Participants | 8 | 6 | 5 | 0 | 19 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 3 | 0 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine in Study MET59: Group 1, measured over Day 30 (post-vaccination) in study MET59.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants in Group 1 with a vaccine seroresponse against meningococcal serogroups A, C, Y, and W at Day 30 after vaccination. Antibody titers are measured with hSBA. The response definition depends on the baseline titer: participants with a pre-vaccination titer below 1:8 must reach a post-vaccination titer greater than or equal to 1:16, while participants whose pre-vaccination titer is at least 1:8 must have a four-fold or greater increase from baseline.
This baseline-dependent definition distinguishes reaching a response threshold from increasing substantially when baseline titers are already higher. It is a binary endpoint for each participant under the stated rule: the participant either meets the seroresponse definition or does not. The reported group percentage would describe the proportion meeting that rule, while a confidence interval would express uncertainty around the estimated proportion.
The registry defines immune response as sufficient if the lower limit of the one-sided 97.5% confidence interval for the percentage with seroresponse is greater than 75%. This criterion evaluates both the observed response percentage and its statistical precision. A percentage alone would not establish that the criterion was met; the confidence interval’s lower limit is part of the rule.
Such an immunogenicity endpoint is used to characterize an antibody response, not to measure the frequency of meningococcal disease. The registry record does not report the primary endpoint percentage or its confidence interval, so whether the stated sufficiency criterion was met is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted registry information describes the endpoint and the threshold for judging immune-response sufficiency, but it does not include the primary endpoint estimate. There is therefore no reported Group 1 seroresponse percentage or confidence interval to interpret against the criterion. Whether the lower limit of the one-sided 97.5% confidence interval exceeded 75% is not reported in the registry record. A conclusion that the criterion was met or not met cannot be drawn from the endpoint definition alone.
The study has four groups with different prior vaccination histories or concomitant vaccination. Those design features define relevant contexts for the immune-response assessments, but the primary outcome title refers to Group 1 rather than to a contrast between groups. The registry record does not report a primary comparison of MenACYW alone against either serogroup B vaccine combination. It would therefore be inappropriate to describe the primary endpoint as establishing whether concomitant vaccination changes the response.
The endpoint is also specific to the hSBA assay and its prespecified seroresponse rule. It records whether an individual meets a threshold or fold-rise criterion; it does not convey the full distribution of titers. The secondary outcomes include geometric mean titers and seroprotection, which provide different summaries of antibody response, but their results are not reported in the registry record. In general, different summaries can answer different statistical questions: a proportion meeting a rule describes the frequency of qualifying responses, while a geometric mean summarizes titers on a multiplicative scale.
Confidence intervals matter because an observed percentage is an estimate based on the participants included in an analysis. In general, a confidence interval conveys the range of values compatible with the data under the statistical method used; it is not a guarantee that the true value lies within that range. Here, the sufficiency rule specifically uses the lower confidence limit, so uncertainty near the 75% threshold is central to interpretation. Without the estimate and interval, neither the magnitude nor the precision of the primary response can be assessed.
The registry record lists a Per-Protocol Analysis Set 2 for evaluating the MenACYW immune response. The description says it includes participants who received one study dose and had a valid post-vaccination serology result, with no relevant protocol deviation. This population definition is relevant to how broadly the endpoint estimate can be applied: it describes an analysis of participants meeting specified study and measurement conditions, not necessarily every enrolled participant. The complete population description and the number analyzed are not reported in the registry record.
The registry’s safety summary records serious-event counts by group and lists several serious-event terms with percentages. These figures should be read as safety summaries, not as evidence about antibody response. The record does not give enough detail in the available information to establish the timing, relatedness, or clinical context of each event. The counts and listed terms do not replace a full assessment of safety outcomes.
Overall, the available information supports interpretation of the trial’s design and analysis target, but not a conclusion about the observed immune response. It does not establish comparative effectiveness, protection against disease, or the relative effects of the concomitant-vaccine groups. Those questions require results and analyses that are not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is a binary participant-level measure derived from hSBA antibody titers. A participant is classified as having a seroresponse if the participant meets the rule appropriate to their baseline titer. The resulting group percentage is the proportion of participants meeting the definition in the specified analysis population. Because the registry record does not include the Group 1 estimate, no observed proportion can be interpreted.
What does the response definition capture?
The rule accounts for baseline antibody level rather than applying a single post-vaccination cutoff to everyone. For a participant whose pre-vaccination titer is below 1:8, the definition requires a post-vaccination titer greater than or equal to 1:16. For a participant whose pre-vaccination titer is at least 1:8, it requires a four-fold or greater increase from the pre-vaccination value. This construction makes the classification depend on both baseline and follow-up measurement.
As a general statistical point, a binary endpoint can make a response criterion straightforward to apply and summarize, but it discards detail about how far each participant’s value lies above or below the criterion. Participants with different titers may be classified in the same category. The secondary geometric mean titer outcomes can describe antibody levels in a different way, but those outcome results are not reported in the registry record.
How should the confidence interval criterion be read?
The registry’s sufficiency rule is based on whether the lower limit of a one-sided 97.5% confidence interval for the seroresponse percentage is greater than 75%. In general, a confidence interval reflects sampling uncertainty under a specified method and model. A lower limit above the threshold would indicate that the interval’s supported values are above the stated benchmark according to that method. The point estimate by itself is not enough to apply this rule. The estimate and interval are not reported in the registry record, so the criterion’s status cannot be determined.
The record lists the primary outcome’s dispersion as a 95% confidence interval, while its endpoint description states a sufficiency rule using a one-sided 97.5% confidence interval. These descriptions identify confidence intervals for the outcome and for the sufficiency assessment, respectively; the registry record does not provide the numerical interval or further detail about how the reported interval relates to the criterion.
Why does the analysis population matter?
The registry identifies Per-Protocol Analysis Set 2 (PPAS2) as the population for evaluating MenACYW immune response. It is described as including participants who received one dose of study vaccine in MET59 and had a valid post-vaccination serology result with no relevant protocol deviation. In general, analysis restricted to participants meeting such conditions can differ from an analysis of everyone randomized, especially if eligibility for the analysis is related to response or follow-up. The registry record does not report how many participants were included in PPAS2 for the primary outcome, how many were excluded, or the reasons for any exclusions.
Randomization supports fair group assignment in a trial, but an analysis limited to a per-protocol population does not automatically preserve every benefit of comparing all randomized participants. Interpretation depends on the question and the analysis plan. The registry record does not report the detailed statistical plan or a separate intention-to-treat analysis for this endpoint. This does not establish that such an analysis was absent; it means the analysis is not reported in the registry record.
What do the other immune measures add?
The secondary outcomes include percentages with seroresponse and seroprotection, as well as geometric mean titers for serogroups A, C, Y, and W. The brief summary defines seroprotection using an hSBA titer greater than or equal to 1:8. It describes measurements at Day 0 and Day 30 for Groups 1 and 2, and an early post-vaccination assessment at 6 days (±1 day) in a subset of 50 participants per group. The registry record also lists pre-booster antibody persistence outcomes.
In general, these measures complement one another rather than being interchangeable. A seroprotection percentage summarizes the share above a stated titer threshold. A geometric mean titer summarizes a set of titers using a mean on a logarithmic scale, then expresses the result on the original scale. This approach is commonly useful for antibody measurements that vary multiplicatively. The registry record does not report the actual secondary outcome results, their confidence intervals, or the methods used to calculate them.
What can planning illustrations establish?
Any sample-size illustrations should be treated as planning calculations, not as observed power or as a record of the trial’s original design justification. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record does not report the trial’s own sample-size justification or design assumptions. Planning illustrations do not provide evidence that an effect occurred, and they do not compensate for the absence of a reported endpoint estimate.
More generally, power calculations depend on assumptions about the effect, variability or event rate, significance level, and analysis. They are prospective design tools, not a measure of the strength of the observed evidence. The registry record does not report interim analyses, the full statistical analysis plan, or details of adjustments for multiple testing. Those methodological details should not be inferred from the endpoint descriptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple immune-response outcomes across serogroups, time points, and study groups. When several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is evaluated without accounting for the others. General methods for addressing this include specifying a primary outcome in advance, using a testing hierarchy, or adjusting the interpretation of multiple tests. The registry record does not report whether or how multiplicity was addressed for the secondary outcomes.
The primary endpoint’s sufficiency rule is described separately, with a lower confidence-limit criterion. The record does not provide the associated estimate or interval, nor does it describe a broader testing hierarchy linking that criterion to the secondary analyses. It is therefore not possible to determine how the several serogroup-specific outcomes were handled statistically or whether any multiplicity adjustment was used.
Missing-data handling is also not reported in the registry record. The PPAS2 description requires a valid post-vaccination serology result, but that eligibility criterion does not explain how missing measurements were treated in other analyses, how many participants lacked measurements, or whether any imputation or sensitivity analysis was performed. These details matter because an analysis of observed results can be affected if missingness is related to participants’ response or study participation.
The analysis population is described only in part in the registry record. It identifies PPAS2 and gives some inclusion conditions, but the complete population definition, numbers analyzed, and participant flow for the primary endpoint are not reported. The record also does not report a full statistical analysis plan, interim analyses, or the method used to calculate the primary confidence interval. These omissions limit assessment of prespecification, missing-data assumptions, and the robustness of the result.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | 2 | 186 | 1.1% |
| Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | 2 | 184 | 1.1% |
| Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | 2 | 93 | 2.2% |
| Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine | 0 | 92 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: MenACYW Conjugate Vaccine | 0 of 186 |
| Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | 0 of 184 |
| Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | 0 of 93 |
| Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine | 0 of 92 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1: MenACYW Conjugate Vaccine | 129 of 186 |
| Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | 116 of 184 |
| Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | 83 of 93 |
| Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine | 88 of 92 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: MenACYW Conjugate Vaccine | Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine |
|---|---|---|---|---|---|
| Suicidal Ideation | Psychiatric disorders | 1 of 186 | 1 of 184 | 1 of 93 | 0 of 92 |
| Appendicitis | Infections and infestations | 1 of 186 | 1 of 184 | 0 of 93 | 0 of 92 |
| Accidental Overdose | Injury, poisoning and procedural complications | 0 of 186 | 0 of 184 | 1 of 93 | 0 of 92 |
| Major Depression | Psychiatric disorders | 0 of 186 | 0 of 184 | 1 of 93 | 0 of 92 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: MenACYW Conjugate Vaccine | Group 2: MenACYW Conjugate Vaccine (Menveo Vaccine-primed) | Group 3: MenACYW Conjugate Vaccine + Trumenba Vaccine | Group 4: MenACYW Conjugate Vaccine + Bexsero Vaccine |
|---|---|---|---|---|---|
| Injection Site Pain | General disorders | 71 of 186 | 63 of 184 | 77 of 93 | 85 of 92 |
| Myalgia | Musculoskeletal and connective tissue disorders | 61 of 186 | 64 of 184 | 60 of 93 | 58 of 92 |
| Headache | Nervous system disorders | 68 of 186 | 67 of 184 | 41 of 93 | 36 of 92 |
| Malaise | General disorders | 50 of 186 | 47 of 184 | 36 of 93 | 37 of 92 |
| Injection Site Erythema | General disorders | 12 of 186 | 10 of 184 | 15 of 93 | 14 of 92 |
| Injection Site Swelling | General disorders | 10 of 186 | 3 of 184 | 12 of 93 | 15 of 92 |
| Nasopharyngitis | Infections and infestations | 9 of 186 | 6 of 184 | 5 of 93 | 2 of 92 |
| Upper Respiratory Tract Infection | Infections and infestations | 10 of 186 | 8 of 184 | 1 of 93 | 1 of 92 |
Serious events with the highest arm-level rate: accidental overdose (1.1%), major depression (1.1%), suicidal ideation (1.1%), appendicitis (0.5%).
The registry’s serious-event summary gives the number at risk and the number affected for each group. Group 1 lists 186 at risk and 2 affected; Group 2 lists 184 at risk and 2 affected; Group 3 lists 93 at risk and 2 affected; and Group 4 lists 92 at risk and 0 affected. Deaths are listed as 0 in each group. These are the registry counts; they should not be converted into percentages or interpreted as comparative risks without a suitable analysis and more detail about event ascertainment and follow-up.
The registry also lists Accidental Overdose and Major Depression at 1.1% each, Suicidal Ideation at 1.1%, and Appendicitis at 0.5% among the top serious-event terms. The available record does not specify the denominator or group assignment for these term percentages, so they should not be attributed to a particular group. The registry information does not describe event timing, seriousness criteria, relationship to vaccination, or whether terms refer to participants or event reports.
Small counts are descriptive and do not by themselves establish that groups differ. A zero count in a group does not prove that the underlying risk is zero. The serious-event figures also do not summarize all safety outcomes; the record lists other adverse-event counts separately. A full interpretation would require the definitions, observation period, participant-level context, and any statistical comparisons, which are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study was designed to characterize hSBA immune responses after a MenACYW booster in participants previously vaccinated with a quadrivalent meningococcal conjugate vaccine. Its primary endpoint asks whether Group 1 met a defined seroresponse sufficiency criterion at Day 30. The registry record supplies the endpoint definition and criterion, but not the observed Group 1 response percentage or its confidence interval. As a result, the posted information does not establish whether the criterion was met.
The endpoint concerns laboratory antibody measurements, not observed prevention of meningococcal disease. In general, an antibody response can be a useful immunogenicity measure, but it is not the same outcome as clinical disease incidence. No disease outcome results are reported in the registry record. Nor does the primary endpoint, as specified, estimate a comparative effect between MenACYW alone and concomitant administration with Trumenba or Bexsero.
The trial includes groups with different prior vaccination histories and different concomitant vaccines, but the presence of multiple groups is not itself evidence of a statistically supported difference. Such a conclusion would require relevant group estimates, uncertainty intervals, and a clearly defined comparison. The registry record does not report those comparative results for the primary endpoint.
The stated sufficiency threshold is also not equivalent to proving that every participant responds or that the response is permanent. It is a population-level statistical criterion applied to a percentage estimate and its lower confidence limit. Secondary outcomes address seroprotection and geometric mean titers at specified time points, but their numerical findings are not reported in the registry record. The early post-vaccination subset and pre-booster persistence assessments therefore cannot be interpreted from the available results.
The appropriate conclusion is limited: the registry describes a randomized, open-label, parallel-group Phase 3 immunogenicity and safety study with a defined primary endpoint and four study groups. It does not provide the primary endpoint result needed to judge the stated criterion, and it does not support conclusions about clinical protection, comparative response between groups, or the duration of an antibody response.
13. Why This Trial Matters Statistically
This study illustrates why an immunogenicity endpoint must be interpreted together with its response definition, analysis population, and uncertainty interval. The primary outcome is not merely a post-vaccination titer: it classifies response using both baseline and follow-up values. That distinction matters when participants enter with different baseline titers, because one universal post-vaccination threshold would not represent the registry’s stated rule.
It also illustrates the difference between a threshold criterion and a comparative treatment effect. The primary sufficiency question evaluates a confidence-limit benchmark for Group 1. It is not, by itself, a test of whether one group’s response is higher than another’s. Although the trial has four arms, the primary outcome title specifies Group 1, and the registry record does not report a primary between-group comparison. Recognizing that distinction prevents the design from being interpreted as a direct comparative test when the registered primary question is framed around sufficiency.
The trial also provides a useful setting for separating several antibody summaries. Seroresponse classifies participants under a baseline-dependent rule; seroprotection counts participants above a titer threshold; and geometric mean titers summarize the level of antibody measurements. These summaries answer related but different questions. Their results and uncertainty are not interchangeable, and no numerical secondary results are reported in the registry record.
Finally, the record shows why registration details alone may be insufficient for a complete statistical appraisal. The endpoint and some population criteria are described, but the result estimate, full analysis population, missing-data methods, multiplicity handling, and detailed statistical plan are not reported. Without those items, readers can understand the intended statistical question but cannot evaluate the observed evidence or its precision.
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 central limitation for interpreting this trial from the registry record is that the primary endpoint result is not reported. The response percentage and confidence interval are needed to assess the stated sufficiency criterion, so the immune-response conclusion cannot be determined from the available information. Secondary immunogenicity results are also not reported, limiting interpretation across serogroups, time points, and groups.
The primary outcome title specifies Group 1, while the brief summary describes a primary objective involving Groups 1 and 2. The registry record does not explain this difference or provide results for both groups under a common primary analysis. It also does not report a primary comparison among the four groups. Thus, the different prior vaccination histories and concomitant vaccines cannot be evaluated comparatively from the information recorded.
The record identifies PPAS2 but gives only a partial description of its membership. The number included in the primary analysis, the reasons for exclusions, the degree of follow-up, and the treatment of missing serology are not reported in the registry record. This leaves uncertainty about how the analyzed participants relate to the randomized groups.
Further methodological details are not reported in the registry record, including the full statistical analysis plan, multiplicity handling, interim analyses, and the trial’s own sample-size justification. The safety summary provides counts and selected event terms, but not the detail needed to assess timing, relatedness, or group-specific event context. These limitations do not show that the procedures or analyses were inadequate; they restrict what can be concluded from the registry information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Immune Response After a Booster Dose of a Quadrivalent Meningococcal (MenACYW) Conjugate Vaccine When Administered Alone or Concomitantly With a Licensed Meningococcal Serogroup B Vaccine, in Participants Who Received Primary Quadrivalent Meningococcal Conjugate Vaccine (MCV4) — NCT04084769.
- Registry record last updated 2025-09-15; status last verified 2025-09.
- Results first posted 2021-08-30.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT04084769 is a completed randomized, open-label, parallel-group Phase 3 study with enrollment of 570. It evaluated a MenACYW booster in participants previously vaccinated with MenACYW or Menveo, with MenACYW given alone or concomitantly with Trumenba or Bexsero. The primary outcome is the Day 30 percentage with hSBA seroresponse in Group 1, assessed against a lower confidence-limit sufficiency criterion greater than 75%. The registry record describes the response definition and the PPAS2 analysis population, but the primary estimate and confidence interval are not reported in the registry record. Secondary immune-response results, detailed missing-data and multiplicity methods, and the full statistical plan are also not reported. Safety summaries list serious-event counts by group and selected serious-event terms.