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 Immunogenicity, Safety and Tolerability of a Neisseria Meningitidis Serogroup B Bivalent Recominant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Toddlers. (NCT02534935), a randomized phase 2 study. The primary outcome is Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (MnB) Test Strains 1 Month After Vaccination 3.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02534935 |
| Phase | Phase 2 |
| Condition | Meningococcal B Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 396 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Healthy toddlers aged 12 to less than 24 months, with age strata of 12 to less than 18 months and 18 to less than 24 months. The primary endpoint analysis population is described as eligible randomized participants who received scheduled investigational products, had pre- and post-vaccination blood drawn with valid, determinate assay results, and had no important protocol deviation.
Intervention
Bivalent rLP2086 vaccine. The registry record describes 60-mcg and 120-mcg groups in Stage 1, with participants stratified by age. A 120-mcg bivalent rLP2086 group is also listed for the Stage 2 booster phase.
Comparator
The control is described as HAV vaccine in the intervention listing and as HAV/Saline in the adverse-event group listing. The control arm was also stratified by age. The registry record does not provide further detail about the control regimen in the registry record.
Primary question
One month after Vaccination 3, what percentage of participants had hSBA titers at or above the lower limit of quantitation for each of four primary Neisseria meningitidis serogroup B test strains? The registry record describes calculation of percentages and two-sided 95% confidence intervals, but does not report numerical primary endpoint results or a numerical comparison between groups.
The trial was designed to describe immunogenicity, safety, and tolerability in healthy toddlers, and also to assess a booster dose. Its primary endpoint is an assay-based measure of antibody activity against specified test strains. It is not a direct count of meningococcal B disease cases. The reported endpoint definition therefore concerns the proportion crossing assay thresholds at a specified assessment time, rather than the size of any change in titers or a clinical disease outcome.
3. Trial Design
This was a randomized, controlled, observer-blinded, parallel-group Phase 2 study sponsored by Pfizer. The registry record lists enrollment of 396 and a completed status. The recorded study start was 2015-08-31, and primary completion was 2017-08-21. The study title and description identify healthy toddlers in two age strata: 12 to less than 18 months and 18 to less than 24 months.
The trial compared bivalent rLP2086 vaccine groups with a control group. Stage 1 adverse-event groups are listed as 60-mcg bivalent rLP2086, 120-mcg bivalent rLP2086, and HAV/Saline. A separate 120-mcg bivalent rLP2086 group is listed for the Stage 2 booster phase. These labels describe the groups in the registry record; the record details do not provide a full account of the vaccination schedule or explain how participants progressed between stages.
The study included immunogenicity outcomes based on human complement serum bactericidal assay titers, as well as safety and tolerability outcomes. The primary immunogenicity assessment was one month after Vaccination 3. Secondary outcomes include antibody measures at other stated times, titers across specified thresholds, geometric mean titers, local and systemic reactions after booster vaccination, antipyretic use, and adverse-event categories during specified follow-up periods.
Triple masking is recorded, along with observer blinding. The registry record does not explain which trial roles were masked or how masking was maintained. It also does not report the allocation ratio, the detailed randomization procedure, or the protocol's rationale for the planned enrollment.
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: In Stage 1, participants received 60 or 120 microgram (mcg) of bivalent rLP2086 vaccine or HAV/saline at Month 1, 2 and 6, and then followed up for 24 months. In Stage 2, participants who received bivalent rLP2086 during Stage 1 had a follow up visit at Month 24. Further participants who received 120 mcg bivalent rLP2086 during Stage 1 were eligible for receiving booster vaccination 6 months after Month 24 visit.
Stage 1: 24 Months
| Stage | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| STARTED | 44 | 220 | 132 |
| COMPLETED | 44 | 210 | 127 |
| NOT COMPLETED | 0 | 10 | 5 |
Reasons for not completing this period:
| Reason | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| Withdrawal by Subject | 0 | 3 | 3 |
| No longer willing to participate in study | 0 | 1 | 1 |
| No longer meets eligibility criteria | 0 | 3 | 0 |
| Lost to Follow-up | 0 | 1 | 1 |
| Adverse Event | 0 | 2 | 0 |
Stage 2: 8 Months
| Stage | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| STARTED | 40 | 174 | 0 |
| COMPLETED | 40 | 170 | 0 |
| NOT COMPLETED | 0 | 4 | 0 |
Reasons for not completing this period:
| Reason | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| Moved away/parents resigned from study | 0 | 4 | 0 |
Stage 2: Booster Phase (6 Months)
| Stage | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| STARTED | 0 | 148 | 0 |
| COMPLETED | 0 | 147 | 0 |
| NOT COMPLETED | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 |
|---|---|---|---|
| Not received booster vaccination | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All eligible participants randomized to study received,scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here,overall number of participants analyzed (N) signifies number of participants evaluable for this outcome measure.
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: Safety population included all participants who received at least 1 dose of the investigational product (rLP2086, HAV vaccine or saline) and had safety data available.
| Characteristic | Unit | Group 1: 60- mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months) | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | Total |
|---|---|---|---|---|---|
| Participants analysed | 44 | 220 | 132 | 396 | |
| Age, Continuous | months | 16.9 (SD 4.08) | 17.4 (SD 3.54) | 17.3 (SD 3.58) | 17.3 (SD 3.61) |
| Sex: Female, Male: Female | Participants | 21 | 114 | 74 | 209 |
| Sex: Female, Male: Male | Participants | 23 | 106 | 58 | 187 |
| Race/Ethnicity, Customized: Race: White | Participants | 37 | 210 | 127 | 374 |
| Race/Ethnicity, Customized: Race: Asian | Participants | 5 | 2 | 1 | 8 |
| Race/Ethnicity, Customized: Race: Other | Participants | 2 | 8 | 4 | 14 |
| Race/Ethnicity, Customized: Ethnicity: Hispanic | Participants | 0 | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Ethnicity: Non-Hispanic | Participants | 44 | 218 | 132 | 394 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (MnB) Test Strains 1 Month After Vaccination 3, measured over 1 month after Vaccination 3.
| 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 with a serum bactericidal assay using human complement (hSBA) titer at or above the lower limit of quantitation (LLOQ) for each of the four primary meningococcal B test strains, measured one month after Vaccination 3. The LLOQ is strain-specific: 1:16 for PMB80 (A22), and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44). The registry record says the percentage was calculated with a corresponding two-sided 95% confidence interval for each strain.
This endpoint converts assay results into a proportion meeting a prespecified threshold. In general, an assay threshold can make results easier to interpret as the share of participants whose measured titer reaches a defined level. The threshold is not the same for every strain in this trial, so the four strain-specific percentages should be understood as separate outcomes, not as a single combined result.
The endpoint is used to describe immunogenicity, meaning the measured antibody response, rather than the occurrence of clinical meningococcal disease. The registry record does not report the numerical percentages, confidence limits, or between-group estimates for this primary endpoint. It also does not provide the complete assay analysis details beyond the thresholds and analysis-population description stated in the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint asks how often participants reached a strain-specific hSBA threshold at a defined assessment time. Its statistical summary would ordinarily include a percentage and a confidence interval for each of the four strains. The registry record describes that approach, including two-sided 95% confidence intervals, but does not report the numerical primary endpoint results. Consequently, no estimate of the observed response proportion or its precision can be stated from the registry record.
There is also no numerical primary comparison between vaccine and control groups in the registry record. A description of the endpoint and planned summary is not itself evidence of a difference between groups. Without the posted group-level outcome values and an analysis estimate, the direction and magnitude of any observed contrast cannot be characterized. The record lists 25 outcome measures and zero analyses in the registry record reported for this analysis, so the registry information available does not support a reconstruction of the primary efficacy-style comparison.
In general, a confidence interval conveys uncertainty around an estimated quantity. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. The interval does not correct for possible bias, address whether the endpoint is clinically meaningful, or establish that a group difference exists. Since no interval endpoints are reported for the primary outcome, the precision of the immunogenicity estimates cannot be evaluated.
The registry does contain adverse-event counts for several groups and follow-up periods. Those counts describe safety information as recorded, but they do not fill the gap in primary immunogenicity results. The groups are listed with different numbers at risk, and adverse-event counts alone do not establish a causal relationship to vaccination. The registry record does not provide a statistical comparison of these safety counts or an adjusted analysis.
The appropriate reading is therefore limited: the record defines a randomized trial, its primary assay-based endpoint, strain-specific thresholds, and several safety outcomes. It does not provide numerical primary endpoint results from which to assess response proportions or compare groups. Any conclusion about an observed immunogenicity effect or the precision of a treatment contrast would go beyond the results reported in the registry record.
9. Statistical Methods Explained
The methods described for the primary endpoint focus on a binary summary: whether each participant's measured hSBA titer is at or above the LLOQ for a given strain. The registry record says the percentage of participants meeting that criterion was calculated, together with a two-sided 95% confidence interval. The analysis is specified separately for each of the four primary test strains.
What does a percentage estimate?
In general, a percentage summarizes the fraction of analyzed participants who meet a defined condition. For this trial, that condition is reaching the strain-specific LLOQ at the assessment one month after Vaccination 3. Such an estimate is straightforward to describe, but it depends on which participants have usable measurements and satisfy the analysis-population criteria. The record's population description includes eligibility, randomization, receipt of scheduled investigational products, pre- and post-vaccination blood draws, valid and determinate assay results, and no important protocol deviation.
The population description does not give a complete account of all analysis decisions or explain how any departures from those criteria were handled. The registry record does not report the numerical denominators used for the primary endpoint by group and strain. Without those denominators and outcome counts, the percentage estimates cannot be checked or reproduced.
What does a confidence interval add?
In general, a confidence interval communicates statistical uncertainty around an estimate. It is not a guarantee that the true value falls within the particular interval, and it does not remove uncertainty due to study conduct, selection, measurement, or model assumptions. For a percentage, interval width is influenced by the amount of information and by the estimated proportion. The registry record identifies two-sided 95% confidence intervals but does not state the interval method, so the precise calculation procedure is not reported in the registry record.
Because the primary endpoint has four strain-specific results, each result needs to be read in relation to its own assay threshold and confidence interval. A value for one strain is not interchangeable with a value for another. The threshold for PMB80 (A22) is 1:16; the thresholds for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44) are 1:8. These assay cutoffs define the binary endpoint, but do not provide the actual observed proportions.
Why can results across strains require care?
In general, several related outcomes create an interpretation issue: examining multiple estimates can make chance patterns more likely to appear noteworthy, particularly if results are selected after inspection. Whether and how to control for multiplicity depends on the prespecified testing strategy and the intended claims. The registry record does not report a multiplicity procedure or a hierarchy for interpreting the four primary strain outcomes. The results therefore cannot be interpreted as a documented family-wise testing plan from the record details available.
The registry lists secondary immunogenicity outcomes, including percentages above other hSBA thresholds, geometric mean titers, and measurements at additional time points. It also lists safety outcomes for local reactions, systemic events, antipyretic use, and adverse-event categories. In general, a larger collection of endpoints increases the importance of distinguishing prespecified primary questions from supportive or exploratory summaries. The registry record does not report how these multiple outcomes were prioritized or adjusted statistically.
What do the planning assumptions mean?
The planning illustration is described as based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also considers fractions of the observed effect. These are planning assumptions, not the trial's reported primary outcome analysis. The record does not report the trial's own sample-size justification, and the planning illustration should not be read as observed power. A sample-size calculation is a prospective illustration of the information a hypothetical design might require under its assumptions; it does not establish what effect the trial actually observed or how precisely it estimated that effect.
In general, power is a property of a design under assumed conditions, not a measure of the probability that a particular result is true. The planning assumptions stated in the record do not substitute for an observed estimate, its confidence interval, or a prespecified statistical analysis. Numerical planning outputs are not reported in the record details available for this analysis.
What can be inferred from the analysis listing?
The record details list zero analyses, and the primary outcome is identified as having several categories or time points that were not reduced to a single comparison. This means the available information does not support a single reconstructed effect estimate. The endpoint definition and analysis-population description can be explained, but a group contrast, inferential test, or assessment of statistical significance cannot be recovered. No adjustment, model, or missing-data procedure should be assumed where it is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint concerns four separate test strains, each with its own LLOQ and intended percentage estimate. The registry record states that two-sided 95% confidence intervals were calculated, but does not report a multiplicity adjustment, a testing hierarchy, or a rule for making a joint claim across strains. Whether any adjustment was planned or used is not reported in the registry record. Accordingly, the strain-specific confidence intervals should not be treated as evidence that a family of comparisons was controlled for multiplicity.
The record lists 25 outcome measures, including immunogenicity assessments at different times and thresholds, geometric mean titers, and safety outcomes. The registry record does not describe how these outcomes were prioritized for confirmatory testing, whether analyses were exploratory, or how multiplicity across the broader outcome set was addressed. No single primary comparison is available in the reported analyses.
For the primary analysis population, the record describes eligible randomized participants who received scheduled investigational products, had pre- and post-vaccination blood drawn with valid, determinate assay results, and had no important protocol deviation. This is a selected analysis population rather than a simple statement that all randomized participants were analyzed. The record does not report the number excluded under each criterion, the amount or pattern of missing assay data, or a sensitivity analysis using another population.
Procedures for missing data, invalid assays, protocol deviations, and participants without a post-vaccination measurement are not reported in the registry record. The record also does not state whether missing values were imputed or whether analyses followed an intention-to-treat principle. These omissions limit assessment of how the analysis population may differ from the randomized population and how robust any endpoint estimates would be to missing measurements.
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: 60- Microgram (mcg) Bivalent rLP2086 (>=12 Months to <24 Months): Stage 1 | 4 | 44 | 9.1% |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months):Stage 1 | 19 | 220 | 8.6% |
| Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | 8 | 132 | 6.1% |
| 120-mcg Bivalent rLP2086: Stage 2 Booster Phase | 2 | 147 | 1.4% |
| Group 1: 60-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 0 | 44 | 0.0% |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 3 | 220 | 1.4% |
| Group 3: HAV/Saline (>=12 Months to <24 Months): Follow up | 0 | 132 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: 60- Microgram (mcg) Bivalent rLP2086 (>=12 Months to <24 Months): Stage 1 | 0 of 44 |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months):Stage 1 | 0 of 220 |
| Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | 0 of 132 |
| 120-mcg Bivalent rLP2086: Stage 2 Booster Phase | 0 of 147 |
| Group 1: 60-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 0 of 44 |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 0 of 220 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1: 60- Microgram (mcg) Bivalent rLP2086 (>=12 Months to <24 Months): Stage 1 | 43 of 44 |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months):Stage 1 | 209 of 220 |
| Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | 113 of 132 |
| 120-mcg Bivalent rLP2086: Stage 2 Booster Phase | 121 of 147 |
| Group 1: 60-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 0 of 44 |
| Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | 0 of 220 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: 60- Microgram (mcg) Bivalent rLP2086 (>=12 Months to <24 Months): Stage 1 | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months):Stage 1 | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | 120-mcg Bivalent rLP2086: Stage 2 Booster Phase | Group 1: 60-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up |
|---|---|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | 0 of 44 | 3 of 220 | 1 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Bronchitis | Infections and infestations | 0 of 44 | 1 of 220 | 2 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Pneumonia | Infections and infestations | 0 of 44 | 3 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Tonsillitis | Infections and infestations | 1 of 44 | 2 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Bronchiolitis | Infections and infestations | 0 of 44 | 2 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Otitis media | Infections and infestations | 0 of 44 | 2 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Viral tonsillitis | Infections and infestations | 0 of 44 | 2 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Eyelid ptosis | Eye disorders | 0 of 44 | 1 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Enteritis | Gastrointestinal disorders | 1 of 44 | 0 of 220 | 0 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 0 of 44 | 0 of 220 | 1 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: 60- Microgram (mcg) Bivalent rLP2086 (>=12 Months to <24 Months): Stage 1 | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months):Stage 1 | Group 3: HAV/Saline (>=12 Months to <24 Months): Stage 1 | 120-mcg Bivalent rLP2086: Stage 2 Booster Phase | Group 1: 60-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up | Group 2: 120-mcg Bivalent rLP2086 (>=12 Months to <24 Months): Follow up |
|---|---|---|---|---|---|---|---|
| Irritability | Psychiatric disorders | 31 of 44 | 176 of 220 | 69 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Injection site erythema (redness) | General disorders | 30 of 44 | 137 of 220 | 28 of 132 | 71 of 147 | 0 of 44 | 0 of 220 |
| Injection site pain (tenderness at injection site) | General disorders | 35 of 44 | 160 of 220 | 41 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Decreased appetite (loss of appetite) | Metabolism and nutrition disorders | 22 of 44 | 142 of 220 | 50 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Somnolence (drowsiness) | Nervous system disorders | 23 of 44 | 127 of 220 | 40 of 132 | 0 of 147 | 0 of 44 | 0 of 220 |
| Injection site swelling (swelling) | General disorders | 17 of 44 | 103 of 220 | 20 of 132 | 49 of 147 | 0 of 44 | 0 of 220 |
| Pyrexia (fever) | General disorders | 16 of 44 | 82 of 220 | 20 of 132 | 15 of 147 | 0 of 44 | 0 of 220 |
| Injection site pain | General disorders | 0 of 44 | 0 of 220 | 0 of 132 | 103 of 147 | 0 of 44 | 0 of 220 |
| Upper respiratory tract infection | Infections and infestations | 6 of 44 | 58 of 220 | 34 of 132 | 3 of 147 | 0 of 44 | 0 of 220 |
| Viral upper respiratory tract infection | Infections and infestations | 5 of 44 | 45 of 220 | 23 of 132 | 5 of 147 | 0 of 44 | 0 of 220 |
Serious events with the highest arm-level rate: enteritis (2.3%), otitis media chronic (2.3%), tonsillitis (2.3%), cerebellar ataxia (2.3%), adenoidal hypertrophy (2.3%).
The registry record lists serious-event counts for the Stage 1 groups and for follow-up. In Stage 1, the 60-mcg bivalent rLP2086 group lists 4 serious events among 44 at risk; the 120-mcg group lists 19 among 220; and the HAV/Saline group lists 8 among 132. The Stage 2 booster-phase 120-mcg group lists 2 serious events among 147 at risk. In follow-up, the listed serious-event counts are 0 among 44 for the 60-mcg group, 3 among 220 for the 120-mcg group, and 0 among 132 for the HAV/Saline group.
These are counts recorded for the stated groups and periods, not adjusted comparisons. The registry record lists 0 deaths for each of these groups. It also lists several serious-event terms with percentages, including Enteritis, Otitis media chronic, Tonsillitis, Cerebellar ataxia, and Adenoidal hypertrophy at 2.3%, and Bronchitis at 1.5%. The record details do not establish that these events were caused by vaccination.
In general, safety counts require attention to the group, follow-up period, and definition used. The registry record does not report a statistical comparison of these serious-event counts or further details needed to assess event timing and attribution. The different groups and periods should not be collapsed into an overall treatment effect.
12. What the Result Does, and Does Not, Mean
The registry record establishes the question the trial was designed to address: whether toddlers met strain-specific hSBA titer thresholds one month after Vaccination 3, alongside the study's safety and tolerability assessments. It also describes the randomized, controlled, observer-blinded design and identifies the vaccine, control, age strata, and primary endpoint population. These are useful features for understanding the planned inquiry.
The record does not report numerical primary endpoint results. It therefore does not show the percentage meeting each threshold, the uncertainty around those percentages, or a numerical contrast between the vaccine and control groups. It cannot support a statement about the size or direction of an observed immunogenicity difference. The described endpoint is an assay measure, not a count of meningococcal B disease cases.
In general, reaching an assay threshold is a measurable laboratory outcome, but its meaning depends on the assay, threshold, population, and clinical context. The endpoint alone does not establish the degree or duration of protection against disease. The registry entries do not provide clinical disease results, so disease prevention cannot be inferred from the endpoint definition.
The adverse-event counts add descriptive safety information, including serious-event counts and deaths as recorded for particular groups and periods. They do not, by themselves, establish that an event was caused by a study vaccine or that event rates differ between groups. The registry record does not report inferential safety comparisons or a full account of event attribution.
The most defensible conclusion is about scope rather than effect: this was a trial designed to describe immunogenicity, safety, and tolerability in healthy toddlers, with a booster assessment also identified. The available registry information specifies outcomes and some safety counts, but does not report the numerical primary immunogenicity results needed to judge the observed response or its precision.
13. Why This Trial Matters Statistically
This trial illustrates the difference between defining an outcome and reporting its result. The primary endpoint is specified in measurable terms: the proportion meeting hSBA thresholds for four strains at a stated time after vaccination. The record also identifies the corresponding confidence-interval approach. Yet without the numerical estimates and their intervals, the endpoint definition cannot answer how many analyzed participants met the thresholds or how precisely those proportions were estimated.
That distinction matters in clinical research because a clear endpoint improves interpretability only when paired with transparent results and analysis details. Here, the strain-specific thresholds make it important to keep each assay result distinct. The separate thresholds and multiple outcomes also make the multiplicity plan relevant, but that plan is not reported in the registry record.
The trial's age stratification and booster phase are additional design features that shape the questions being studied. They create clinically distinct groups and assessment periods, but the record details do not provide enough numerical primary results to compare those groups. Reporting enrollment and a completed status does not replace outcome-specific denominators, estimates, or uncertainty intervals.
The safety information also demonstrates why counts need context. Serious-event counts are reported for separate groups and periods, but the record does not give statistical comparisons or establish causality. Separating descriptive safety summaries from comparative claims prevents the counts from being read as proof of a treatment effect.
Statistically, the registry record is informative about design and endpoint construction, while remaining limited for judging the primary outcome. The missing numerical primary estimates, analysis details, and multiplicity and missing-data procedures restrict what can be concluded from the record. This distinction is important when reading a trial record: registration details, outcome definitions, and outcome results are different kinds of evidence.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting the primary question is that numerical results for the primary endpoint are not reported in the registry record. There are no strain-specific percentages, confidence limits, or reported group comparisons in the registry record for this analysis. The record therefore does not allow assessment of the magnitude or precision of the immunogenicity estimates.
The registry describes an analysis population requiring receipt of scheduled investigational products, pre- and post-vaccination blood draws, valid and determinate assays, and no important protocol deviation. It does not report how many randomized participants met or failed each criterion, nor does it provide the primary analysis denominators by group and strain. The extent and handling of missing or invalid assay results are not reported in the registry record.
The detailed randomization procedure, allocation ratio, full vaccination schedule, and masking implementation are not reported in the registry record. The record also does not provide the protocol's sample-size justification, the statistical analysis plan, an interim-analysis description, or a multiplicity procedure. These omissions limit evaluation of how design decisions related to the intended comparisons.
The primary endpoint is based on assay titers rather than observed disease outcomes. The registry record does not report clinical meningococcal B disease results. Safety information is available as counts in named groups and periods, but the registry entries do not provide comparative analyses or enough detail to establish event attribution. The serious-event summaries should therefore be read descriptively rather than as causal or comparative estimates.
Finally, the listed outcome set includes immunogenicity and safety measures at multiple thresholds and times. The registry record does not explain how those outcomes were prioritized or how results across them were intended to be interpreted. These limitations are specific to the information recorded and should not be mistaken for evidence that an unreported procedure was or was not used.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity, Safety and Tolerability of a Neisseria Meningitidis Serogroup B Bivalent Recominant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Toddlers. — NCT02534935.
- Registry record last updated 2021-09-27; status last verified 2021-08.
- Results first posted 2018-04-17.
- 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
NCT02534935 is a completed, randomized, controlled, observer-blinded, parallel-group Phase 2 study sponsored by Pfizer. It enrolled healthy toddlers aged 12 to less than 24 months and evaluated bivalent rLP2086, with age strata of 12 to less than 18 months and 18 to less than 24 months. The record lists 60-mcg and 120-mcg vaccine groups, a HAV/Saline control group, and a 120-mcg booster-phase group.
The primary endpoint was the percentage with hSBA titers at or above strain-specific LLOQs one month after Vaccination 3, with two-sided 95% confidence intervals described. Numerical primary endpoint results and a numerical group comparison are not reported in the registry record. Safety counts are listed for serious events, other events, and deaths across specified groups and periods. Details of multiplicity handling, missing-data procedures, and the trial's sample-size justification are not reported in the registry record.