Safety and Immunogenicity of PanBlok Influenza Vaccine in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of PanBlok Influenza Vaccine in Healthy Adults (NCT01147068), a randomized phase 1, phase 2 study. The primary outcome is Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age..

2. Clinical Question

The primary result is an immunogenicity measure, not a clinical outcome such as prevention of influenza illness. The registry reports seroconversion percentages for each group and unadjusted comparisons with placebo. The observed percentages were 0.0 for placebo, 32.0 for PanBlok 135µg without adjuvant, and 15.0 for PanBlok 45µg without adjuvant. In the GLA-SE groups, the percentages ranged from 66.0 to 82.0 across the four dose levels. These are descriptive results from the registry record; they do not establish how the vaccine would perform in other populations or against clinical disease.

3. Trial Design

This was a randomized, quadruple-masked, placebo-controlled Phase 1 and Phase 2 study. The registry lists enrollment of 392 and a completed status. It records the study start as 2010-06 and primary completion as 2011-10. The stated purpose was to investigate the safety and immunogenicity of recombinant hemagglutinin vaccine at four dose levels in adjuvanted formulations and two dose levels in unadjuvanted formulations.

Seven groups are represented in the primary results: placebo; PanBlok 135µg without adjuvant; PanBlok 45µg without adjuvant; and four PanBlok doses with GLA 1.0µg in a 2% stable emulsion. Each group description specifies two 0.5 mL intramuscular injections 21 days apart. The active formulations therefore vary in the amount of recombinant hemagglutinin, while the listed adjuvanted groups share the same stated amount of GLA and emulsion concentration.

For the primary outcome, the registry identifies an analysis population of randomized participants who received study vaccine and had Day 0 and Day 42 efficacy data. It says the results were generated by Southern Research Institute using whole virus. The reported group sizes for this outcome range from 53 to 57 participants, with 57 in placebo. These denominators are the participants represented in the endpoint results; the registry does not provide a full account of participant flow from enrollment through each analysis population.

Randomization and masking are features of the design that can reduce systematic differences in group assignment and assessment. The registry classifies the model as single group despite listing randomized treatment groups and comparative results; the meaning of that model label is not explained in the registry record. Details such as the allocation ratio, randomization method, masking procedures, and site structure are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Subjects whose laboratory values were exclusionary were not randomized. Women of child-bearing potential were required to have a negative pregnancy test.

Only the first 6 of 7 groups are shown.

Subjects That Received 1st Dose

Subjects That Received 2nd Dose

Reasons for not completing this period:

Subjects That Completed Safety Follow-up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized subjects who received study vaccine and had Day 0 and Day 42 efficacy data. The analysis results are generated by Southern Research Institute on the intention to treat efficacy population using whole virus.

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age., measured over 42 Days.

The primary endpoint is the percentage of participants who exhibited seroconversion on Day 42. The registry gives the unit as percentage of participants and reports a 95% confidence interval for each group. Its stated analysis population consists of randomized participants who received study vaccine and had Day 0 and Day 42 efficacy data, with measurement using whole virus.

Seroconversion is used as an immunogenicity outcome: it records whether a participant meets a defined serologic response criterion between the specified assessments. That makes it possible to compare the proportion reaching the response criterion in the vaccine groups and placebo. General statistical interpretation: a binary outcome such as seroconversion retains whether each participant met the criterion, rather than describing the full distribution of antibody measurements. It therefore answers a different question from a geometric mean titer, which summarizes antibody levels across a group.

The registry describes evaluating adjuvanted rHA groups against non-adjuvanted rHA and placebo, including whether response rates and confidence intervals met a regulatory criterion for licensure. The exact seroconversion definition, the numerical regulatory criterion, and any decision rule for combining the rate and its confidence interval are not reported in the registry record. The observed percentages can be interpreted as the recorded group response rates, but they cannot independently establish that the specified regulatory criterion was satisfied.

7. Results Posted in the Registry

• PanBlok 135µg No Adjuvant: 31.5% (17/54) versus 0.0% (0/57) on control; risk difference 31.5 percentage points (95% CI 19.1 to 43.9); unadjusted two-proportion z-test p = <0.001.
• PanBlok 45µg No Adjuvant: 14.8% (8/54) versus 0.0% (0/57) on control; risk difference 14.8 percentage points (95% CI 5.3 to 24.3); unadjusted two-proportion z-test p = 0.003.
• PanBlok 45µg and GLA 1.0µg, SE 2%: 81.5% (44/54) versus 0.0% (0/57) on control; risk difference 81.5 percentage points (95% CI 71.1 to 91.8); unadjusted two-proportion z-test p = <0.001.
• PanBlok 15µg and GLA 1.0µg, SE 2%: 75.0% (42/56) versus 0.0% (0/57) on control; risk difference 75.0 percentage points (95% CI 63.7 to 86.3); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PanBlok 135µg No Adjuvant: 3.6% (2/56) versus 3.3% (2/60) on control; risk difference 0.2 percentage points (95% CI -6.4 to 6.9), risk ratio 1.07 (0.16–7.35); unadjusted two-proportion z-test p = 0.944.
  • PanBlok 45µg No Adjuvant: 3.7% (2/54) versus 3.3% (2/60) on control; risk difference 0.4 percentage points (95% CI -6.4 to 7.2), risk ratio 1.11 (0.16–7.62); unadjusted two-proportion z-test p = 0.915.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PanBlok 135µg No Adjuvant and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PanBlok 45µg No Adjuvant and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results describe a different assessment from the primary endpoint: serologic response rates at Day 21, rather than seroconversion at Day 42. Across the groups, the Day 21 percentages are low, and their confidence intervals are broad. The posted comparisons for the two non-adjuvanted vaccine groups with placebo have risk-difference confidence intervals that include zero, with unadjusted p-values of 0.944 and 0.915. These findings do not provide clear evidence of a difference in those comparisons, but the low response rates and broad intervals also mean that the estimates are imprecise.

The overall secondary pattern is not equivalent to the Day 42 primary pattern. The assessment day and the stated response outcome differ, and the secondary outcome description uses a broader age range than the primary outcome description. It would therefore be inappropriate to interpret the secondary results as a direct measure of the development or decline of the primary response over time. The registry also names geometric mean titers as a secondary outcome, but numerical geometric mean titer results are not reported in the registry record.

Unadjusted secondary results carry less inferential weight when several outcomes and group contrasts are considered. General statistical explanation: testing multiple hypotheses increases the chance of obtaining at least one apparently unusual result even when there is no underlying difference. An adjustment or a prespecified hierarchy can address that issue, but a multiplicity strategy is not reported in the registry record. The secondary comparisons should therefore be read as exploratory descriptions, not as independent confirmation of the primary pattern. The registry contains no posted analyses for the secondary outcomes beyond the reported summaries and comparisons described in the record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age.
• Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either met the seroconversion criterion or did not. The group result is expressed as the percentage of participants meeting that criterion. The registry also reports a 95% confidence interval for each percentage. General statistical explanation: the interval indicates the range of values reasonably compatible with the observed data under the method used to construct it. It reflects sampling uncertainty and does not mean that a fixed proportion of participants has a 95% probability of lying inside the interval.

What does a risk difference describe?

The registry’s comparisons express the difference between the response proportion in a vaccine group and the proportion in placebo. A risk difference of zero would mean equal observed proportions; a positive value means the vaccine group’s observed proportion was higher. The reported placebo response was 0.0%, so the reported comparison estimates correspond to the vaccine-group proportions expressed on the risk-difference scale. For example, the registry reports a risk difference of 0.815 for PanBlok 45µg with GLA-SE, with a 95% confidence interval from 0.711 to 0.918. This is an unadjusted contrast, not a model-adjusted result.

How should the p-values be read?

The unadjusted p-values assess compatibility of the observed comparison with a null hypothesis of no difference, under the assumptions of the test. They do not measure the probability that the null hypothesis is true, and they do not quantify the size or clinical importance of a difference. In the primary comparisons, each unadjusted p-value is below 0.01; the registry reports values of <0.001 for five comparisons and 0.003 for the remaining comparison. These are nominal results because no adjustment for multiple comparisons is reported. The registry record does not give the testing method or specify a familywise error procedure.

Why are confidence intervals useful alongside tests?

A p-value gives limited information about the range of effect sizes compatible with the data. The confidence intervals for risk differences show both the direction and uncertainty of the estimated contrasts. For the primary comparisons with placebo, the reported intervals are above zero. However, interval width remains important: broad intervals allow a wider range of plausible effect sizes. The endpoint confidence intervals also show that uncertainty remains around each group’s response percentage, even where the observed response is high.

What do the sample-size illustrations mean?

The planning illustrations use an observed effect as their starting point and show hypothetical participants per arm under stated assumptions: a two-sided significance level of 0.05, equal allocation, and a normal approximation. Rows consider planning for 100%, 75%, and 50% of the observed effect. General statistical explanation: planning for a smaller effect usually requires a larger sample to distinguish that effect from no difference with a chosen power. These illustrations are not the study’s enrollment target, not a reconstruction of the trial’s original design, and not observed power. The registry record does not report the original sample-size justification or its planning assumptions.

The secondary comparisons illustrate a particular limitation of planning from observed effects when event proportions are low. Their observed risk differences are close to zero, and the planning illustrations consequently yield very large hypothetical sample sizes. Such values are highly dependent on the observed effect used as the planning input. They should not be read as evidence that the trial had or lacked a particular probability of detecting a true effect.

What does a low event proportion do to precision?

When few participants meet a binary response criterion, the estimated proportion can be sensitive to a small number of participants. General statistical explanation: the amount of information in a binary endpoint depends on both the sample size and the distribution of responses. A small sample with few events can therefore produce uncertainty that is large relative to the observed proportion. The Day 21 secondary outcome has low response percentages in every group, and its confidence intervals are broad relative to the estimates. That helps explain why the secondary comparison intervals include zero even though some point estimates differ from placebo.

The reported statistical material includes simple unadjusted comparisons, but the registry record does not provide a fuller statistical analysis plan, model specification, covariate adjustment, or multiplicity strategy. Those omissions limit what can be concluded about the intended inferential framework. The results can still be described as posted, while distinguishing the observed group summaries from any claim about a prespecified confirmatory analysis.

11. Confidence Intervals and Precision

Precision is best judged from the confidence intervals, not from the point estimates alone. For Day 42, the placebo response was 0.0% with a reported interval of 0.0 to 0.0. The vaccine-group intervals are wider: 21.0 to 45.0 for PanBlok 135µg without adjuvant; 8.0 to 27.0 for 45µg without adjuvant; and, among adjuvanted groups, 69.0 to 90.0, 62.0 to 84.0, 53.0 to 77.0, and 58.0 to 82.0. These ranges show uncertainty around the estimated response in each group despite the apparent separation between placebo and the adjuvanted groups.

The risk-difference intervals for the primary comparisons with placebo are 0.191 to 0.439 for 135µg without adjuvant, 0.053 to 0.243 for 45µg without adjuvant, 0.711 to 0.918 for 45µg with GLA-SE, 0.637 to 0.863 for 15µg with GLA-SE, 0.533 to 0.788 for 7.5µg with GLA-SE, and 0.596 to 0.838 for 3.8µg with GLA-SE. Each of these intervals lies above zero. This is evidence of a positive observed difference under the reported unadjusted comparisons, but it does not remove uncertainty about the magnitude of the difference.

General statistical explanation: an interval estimates uncertainty under a sampling model and the available data. It does not cover uncertainty from unreported design choices, missing-data handling, endpoint definitions, or selective reporting. The registry does not report a method for missing data or the exact confidence-interval construction method. Group sizes for the primary endpoint are between 53 and 57 participants, so the estimates remain based on a modest number of observations. The placebo interval of 0.0 to 0.0 should be read in light of the observed zero responses and the stated reported interval, rather than as proof that the underlying response probability is exactly zero.

12. Multiplicity, Missing Data and Analysis Populations

The registry describes several treatment groups, a primary endpoint, and secondary outcomes. It reports unadjusted p-values for comparisons with placebo, but a multiplicity adjustment or testing hierarchy is not reported in the registry record. General statistical explanation: when multiple comparisons are made, the chance of at least one false-positive result can increase if each comparison is judged separately at the same threshold. The primary p-values are therefore nominal; they should not be described as multiplicity-controlled confirmatory evidence.

The primary analysis population is defined as randomized participants who received study vaccine and had Day 0 and Day 42 efficacy data. This definition makes clear that not every randomized participant necessarily appears in the endpoint denominators. However, the registry does not provide a participant disposition accounting for why participants may be absent from an endpoint analysis. A missing-data method, assumptions about missing outcomes, and sensitivity analyses are not reported in the registry record.

The registry’s secondary outcome descriptions refer to healthy adults 18-64 years of age, while the primary description refers to adults 18-49 years of age. The record does not explain the difference in stated age ranges or how it relates to the actual analysis populations. The primary outcome description identifies use of whole virus and analysis by Southern Research Institute, but a fuller statistical analysis plan, including the exact seroconversion definition and the specified comparison methods, is not reported in the registry record.

Interim analyses, stopping rules, sample-size justification, and any prespecified subgroup analyses are not reported in the registry record. Their absence from the record should not be interpreted as evidence that a particular procedure was or was not used. It means that the posted information does not support an assessment of those design and analysis decisions.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: fractured/cracked vertebrae (1.8%), costochondritis (1.8%), left upper lobe lung nodule with organizing abscess (1.8%), ovarian cyst (1.8%), pinched nerve between c3-6 (1.8%).

The safety summaries report serious adverse events and other adverse events by group. Serious adverse events affected 1 participant in placebo, 2 in PanBlok 135µg without adjuvant, 1 in PanBlok 45µg without adjuvant, 1 in the 45µg GLA-SE group, 2 in the 15µg GLA-SE group, 0 in the 7.5µg GLA-SE group, and 3 in the 3.8µg GLA-SE group. The corresponding numbers at risk range from 53 to 60 across these safety groups.

These counts are descriptive. They do not establish whether an event was caused by study vaccine, and they do not provide a reliable basis for comparing uncommon events across groups. The registry lists serious-event terms including fractured/cracked vertebrae, costochondritis, left upper lobe lung nodule with organizing abscess, ovarian cyst, pinched nerve between C3-6, and post-operative infection; each is listed as 1.8%. The record does not provide enough context in these figures to assess the clinical circumstances or attribution for each event. Death counts are not reported in the registry record. The presence of a serious adverse event in a study report should not by itself be interpreted as evidence of causation.

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

The primary result shows that Day 42 seroconversion percentages differed across the randomized groups. The recorded rates were highest in the adjuvanted formulations, lower in the two non-adjuvanted formulations, and zero in placebo. The unadjusted risk-difference intervals for each vaccine group versus placebo lie above zero. These observations describe the posted immunogenicity data and their statistical uncertainty.

They do not establish that any formulation prevents influenza illness, reduces complications, or provides protection over a particular duration. The primary endpoint is seroconversion, not a clinical disease outcome, and the registry does not report clinical influenza outcomes in the results. The data also do not establish that the adjuvant alone caused the differences: the reported groups include multiple formulation and dose differences, and direct adjuvanted-versus-unadjuvanted estimates are not reported in the registry record.

The registry’s endpoint description refers to a regulatory criterion for licensure, but the numerical criterion and its decision rule are not reported in the registry record. Consequently, the posted response rates and confidence intervals cannot be used to determine whether that criterion was satisfied. The lack of a reported multiplicity strategy, the modest endpoint group sizes, and unreported details about missing data also constrain the strength of inferential conclusions.

The results are specific to the studied formulations, assessment time, and described healthy-adult populations. They should not be generalized automatically to other ages, populations, vaccine formulations, or later time points. General statistical interpretation: a randomized comparison can support causal interpretation when the design and analysis assumptions are met, but uncertainty about the actual analysis population, missing data, and unreported analytic procedures remains relevant. The registry record supports a description of the observed immunogenicity pattern, not a broad claim of clinical effectiveness or a complete evaluation of safety.

15. Why This Trial Matters Statistically

Statistically, this study is informative because it reports a binary immunogenicity outcome across placebo, unadjuvanted formulations, and several adjuvanted dose levels. That structure makes the pattern across formulation groups visible: the reported Day 42 response percentages are higher in the adjuvanted groups than in the non-adjuvanted groups, with placebo at zero. The confidence intervals and risk differences make clear that the point estimates are not exact, even where the comparisons with placebo are separated from zero.

The study also illustrates why endpoint definition and assessment time matter. The Day 42 primary endpoint and Day 21 secondary response endpoint are not interchangeable. The registry’s secondary results have low response proportions and broad uncertainty, while the primary results show a different pattern. Interpreting them together requires attention to what was measured, when it was measured, and which age range each outcome describes.

The report is also a useful example of the distinction between an observed effect and a design assumption. Sample-size illustrations based on the observed secondary effects are hypothetical planning calculations, not evidence of the study’s original design or its power. Their sensitivity to the observed effect is particularly relevant when response events are uncommon. A stated sample-size justification, analysis plan, and multiplicity strategy would help readers understand how the study was intended to support its inferences; those details are not reported in the registry record.

Finally, the registry separates immunogenicity findings from safety counts, but neither should be overread. The primary response measure is not a clinical outcome, and the serious adverse event counts are descriptive and uncommon. Sound interpretation depends on matching each conclusion to the outcome and uncertainty actually recorded.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations specific to this record affect interpretation. First, the primary endpoint group sizes are 53 to 57, which leaves appreciable uncertainty around the response estimates. Second, the registry does not report a participant-flow account or missing-data methods, even though the primary analysis population requires Day 0 and Day 42 efficacy data. It is therefore not possible to determine from the posted results how missing endpoint observations were handled or whether their absence could affect the estimates.

Third, the registry gives different age ranges across outcome descriptions: 18-49 years for the primary endpoint and 18-64 years for the secondary outcome descriptions. The relationship between those ranges and the participants included in each result is not explained. Fourth, the outcome is serologic rather than clinical. The posted primary result does not report influenza illness, and the registry results do not establish clinical protection or duration of response.

Fifth, the treatment groups differ in formulation and dose, and the posted comparison estimates are against placebo. Direct contrasts between adjuvanted and unadjuvanted vaccine groups are not reported in the registry record. That restricts conclusions about the independent contribution of the adjuvant. The registry also does not state the exact seroconversion criterion, the statistical method for the confidence intervals, or a multiplicity plan.

Finally, the safety summaries provide counts but not detailed event-level context or causality assessments in the results. Death counts and longer-term safety outcomes are not reported in the registry record. These gaps do not invalidate the posted summaries, but they limit how fully the design, analysis, safety profile, and generalizability can be assessed.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of PanBlok Influenza Vaccine in Healthy Adults — NCT01147068.
• Registry record last updated 2012-11-26; status last verified 2012-10.
• Results first posted 2012-11-26.
• 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.

20. Record Summary

The registry record describes a completed randomized, quadruple-masked, placebo-controlled Phase 1 and Phase 2 study of PanBlok recombinant H5N1 hemagglutinin vaccine in healthy adults. Enrollment was 392. The study compared two unadjuvanted dose levels and four GLA-SE-adjuvanted dose levels with placebo, using two intramuscular injections 21 days apart.

The primary outcome was Day 42 seroconversion. Reported percentages were 0.0% for placebo, 15.0% and 32.0% for the unadjuvanted groups, and 66.0% to 82.0% for the adjuvanted groups. Unadjusted comparisons with placebo had risk-difference confidence intervals above zero. The registry also reports Day 21 secondary response results, but no numeric geometric mean titer results. Multiplicity handling, missing-data methods, the sample-size justification, and the regulatory decision criterion are not reported in the registry record.