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 Development of Read-outs in Healthy, Hepatitis B Virus Naive Adults Vaccinated With the Hepatitis B Surface Antigen (HBsAg) in Combination With a GlaxoSmithKline (GSK) Biologicals' Adjuvant System (NCT01777295), a randomized phase 2 study. The primary outcome is Concentrations of Cytokines and Chemokines - Step 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01777295 |
| Phase | Phase 2 |
| Condition | Hepatitis B |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 81 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults who were naive to hepatitis B virus. The primary endpoint description refers to an According-To-Protocol cohort for innate immunogenicity through Day 60 in Step 1; its definition includes evaluable, protocol-compliant subjects with available data for at least one innate assay, but the complete eligibility wording is not reported in the registry record.
Intervention
The HBsAg/AS group received placebo at Day -30, followed by two doses of the adjuvanted hepatitis B surface antigen candidate vaccine at Day 0 and Day 30.
Comparator
The Engerix-B group received placebo at Day -30, followed by Engerix-B at Day 0, Day 30 and Day 180. The registry record describes the two groups and their schedules; further details of the comparison are not reported in the registry record.
Primary question
The registered primary endpoint is concentrations of cytokines and chemokines at Day -30, before placebo administration. It describes baseline plasma measurements, rather than a reported post-vaccination comparison. The numerical concentrations and any comparison between groups are not reported in the registry record.
The study’s stated aim was to develop immunological read-outs and technologies for characterizing early immune responses, their kinetics, and adaptive immune responses to adjuvanted vaccines. It also planned to evaluate reactogenicity in the study population. Those aims frame the scientific question, but the registry record does not report numerical primary-endpoint results or an inferential analysis addressing whether the groups differed.
The primary endpoint lists a panel of cytokines and chemokines, with results intended to be expressed as medians and inter-quartile ranges in pg/mL. Because the recorded measurement time was before placebo administration, these measurements describe a baseline time point. They cannot by themselves show how either vaccine schedule changed immune markers after vaccination. Post-vaccination values and estimates of change are not reported in the registry record.
3. Trial Design
This was a Phase 2, randomized, single-masked, parallel study with an enrollment of 81. It was conducted in healthy adults naive to hepatitis B virus, and the listed condition is Hepatitis B. The registry record identifies GlaxoSmithKline as the sponsor and reports the study as completed. The start date was 2013-02-25 and the primary completion date was 2016-05-17.
The registry describes two groups. Subjects in the HBsAg/AS group received one dose of placebo at Day -30, then two doses of HBsAg/AS at Day 0 and Day 30. Subjects in the Engerix-B group received one dose of placebo at Day -30, then three doses of Engerix-B at Day 0, Day 30 and Day 180. The interventions are listed as biological interventions. Further information about allocation procedures, the identity of the masked party, and implementation of masking is not reported in the registry record.
The design is parallel, so the registry describes separate groups following their assigned schedules. Randomization is recorded, but the method used to generate or conceal allocation is not reported in the registry record. The registry’s classification as single-masked does not specify who was masked. No additional design details should be inferred from those labels.
The stated focus combines development of immune measurements with an evaluation of reactogenicity. The primary endpoint is a panel of plasma cytokine and chemokine concentrations at Day -30, before placebo administration. Secondary outcomes include antibody concentrations and several categories of solicited symptoms and adverse events. The registry lists 104 outcome measures and 0 analyses. The absence of listed analyses means numerical estimates, uncertainty intervals, and test results cannot be interpreted from this record.
The registry record does not report a sample-size justification, a detailed statistical analysis plan, or whether any interim analyses were conducted. The enrollment figure is not a basis for inferring the number included in any particular endpoint analysis, because endpoint-specific analysis counts 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.
Overall Study
| Stage | HBsAg/AS_1+2 Group | Engerix-B_1+2 Group |
|---|---|---|
| STARTED | 40 | 41 |
| COMPLETED | 36 | 38 |
| NOT COMPLETED | 4 | 3 |
Reasons for not completing this period:
| Reason | HBsAg/AS_1+2 Group | Engerix-B_1+2 Group |
|---|---|---|
| Withdrawal by Subject | 2 | 2 |
| Pregnancy | 0 | 1 |
| Personal problem | 1 | 0 |
| Investigator call for AEs check | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analyses were performed on the According-To-Protocol (ATP) cohort for innate immunogenicity up to Day 60 (step 1 only), which included all evaluable subjects, who complied with the protocol and for whom data concerning innate immunogenicity were available for at least one innate assay at one post-vaccination time point (up to Day 60).
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.
| Characteristic | Unit | HBsAg/AS_1+2 Group | Engerix-B_1+2 Group | Total |
|---|---|---|---|---|
| Participants analysed | 40 | 41 | 81 | |
| Age, Continuous | Years | 39.2 (SD 4.1) | 37.5 (SD 5.9) | 38.4 (SD 5.2) |
| Sex: Female, Male: Female | Participants | 25 | 26 | 51 |
| Sex: Female, Male: Male | Participants | 15 | 15 | 30 |
| Race/Ethnicity, Customized: Geographic ancestry – African Heritage / African American | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Geographic ancestry – White - Arabic / North African Heritage | Participants | 1 | 2 | 3 |
| Race/Ethnicity, Customized: Geographic ancestry – White - Caucasian / European Heritage | Participants | 38 | 39 | 77 |
6. Primary Endpoint
The registry lists the primary outcome as Concentrations of Cytokines and Chemokines - Step 1, measured over At Day -30 prior to placebo administration.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | pg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is concentrations of cytokines and chemokines in plasma, expressed in pg/mL. The registry specifies the median as the summary measure and the inter-quartile range as the measure of dispersion. Measurements were taken at Day -30, before placebo administration, and were measured by Multiplex in plasma. The listed panel includes immune signalling and inflammatory markers, including cytokines and chemokines.
In general, a median describes the middle of an ordered set of measurements, while the inter-quartile range describes the spread of the central portion of those measurements. These summaries can describe a distribution without requiring it to be symmetric. The registry does not report the actual medians or inter-quartile ranges for the listed markers, so their values and variability cannot be assessed.
Baseline immune-marker measurements can provide descriptive information about the measured markers before the study vaccine schedules begin. This is a general interpretation of baseline measurements, not a reported finding from this study. Because the registered time point precedes placebo administration, it does not directly quantify a vaccine-associated change. Numerical results at later time points, comparisons between groups, and estimates of change from baseline are not reported in the registry record.
The study’s stated aim was to develop read-outs for characterizing early and adaptive immune responses. The endpoint therefore concerns measurement of immune markers, but the registry record does not establish how well any marker served as a read-out or whether the measurements distinguished responses between schedules.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a baseline immune-marker endpoint, not a numerical treatment-effect estimate. It specifies median plasma concentrations and inter-quartile ranges for cytokines and chemokines at Day -30, before placebo administration. The measured values are not reported in the registry record. As a result, there is no posted primary-endpoint estimate to interpret for magnitude, variability, or a difference between groups.
The endpoint’s timing matters. A measurement before placebo administration characterizes a pre-intervention time point; it cannot alone describe a response to the later vaccine schedules. To assess a change over time, numerical measurements at relevant follow-up times and a clearly described comparison would be needed. Such results are not reported in the registry record. This does not establish that no such data were collected; it means they are not available in the record.
The registry lists 104 outcome measures but 0 analyses. This indicates that the record contains outcome listings without listed analysis results. The secondary outcomes cover anti-HBs antibody concentrations, solicited symptoms, unsolicited adverse events, serious adverse events, potential immune-mediated disorders, and medical-attention events. Their outcome names do not substitute for numerical findings. Counts, estimates, uncertainty intervals, and tests for those outcomes are not reported in the registry record, except for the limited safety figures described separately.
In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval represents the range of values compatible with the data and the method used, under its assumptions. No confidence intervals for the immune-marker outcomes are reported in the registry record, so statistical precision cannot be assessed. Nor is a p-value or other inferential comparison for the primary endpoint reported.
The recorded enrollment and the two group-specific safety denominators do not supply endpoint-specific analysis populations. The primary endpoint description refers to an ATP cohort for innate immunogenicity through Day 60 in Step 1, but the registry record does not provide the number analyzed for each marker or the corresponding numerical results. Therefore, the enrollment figure should not be treated as the analyzed sample size for the primary endpoint.
The listed schedule and study objective provide context for the measurements, but they do not establish an effect of either schedule. Without reported endpoint estimates and a specified analysis, the record cannot support a conclusion about differences in immune-marker concentrations or changes over time. Interpretation should remain limited to the design, endpoint definition, and safety counts actually recorded.
9. Statistical Methods Explained
What does the median and inter-quartile range describe?
The registry specifies that cytokine and chemokine concentrations are summarized using the median and inter-quartile range. In general, the median is the central value when observations are ordered. The inter-quartile range describes the spread between the lower and upper quartiles. Together, these summaries convey a typical value and the spread of the central part of a distribution. They do not show every observation, and they do not by themselves estimate a difference between groups.
These summaries are often useful when measurements are not well represented by a symmetric distribution. This is a general statistical consideration, not a statement about the actual distributions in this study. The registry record does not report individual measurements, distribution plots, medians, or inter-quartile ranges. It is therefore not possible to assess the shape or spread of the measured cytokine and chemokine values.
What does the measurement time imply?
The registered timeframe is Day -30, before placebo administration. This identifies the measurement as occurring before the scheduled placebo and vaccine doses. In general, measurements taken before an intervention can describe a baseline state. Estimating change requires measurements at later time points and a defined approach to comparing those measurements with baseline. The registry record does not report numerical values at follow-up or an analysis of change.
The study aim concerns early immune responses, their kinetics, and adaptive immune responses, but the primary endpoint description available in the registry identifies this baseline measurement. The endpoint’s stated time is not evidence of a post-vaccination effect. Numerical measurements for other time points and analyses of response kinetics are not reported in the registry record.
What can a group comparison establish?
In general, a comparison between randomized groups can estimate a difference associated with assignment to their respective schedules, subject to the analysis population, outcome definition, missing data, and assumptions used. A difference estimate alone does not convey precision; a confidence interval can show the uncertainty around that estimate. A test statistic or p-value addresses a different question and should be interpreted alongside the estimated magnitude and uncertainty.
For this trial, the registry identifies randomized parallel groups and gives their schedules, but does not report a numerical primary-endpoint comparison, confidence interval, or p-value. No comparative effect should be inferred from the group descriptions or from the study’s stated aims.
How should the analysis population be understood?
The primary endpoint description names an According-To-Protocol cohort for innate immunogenicity through Day 60 in Step 1. It describes inclusion of evaluable subjects who complied with the protocol and had data concerning innate immunogenicity for at least one innate assay at a post-vaccination visit; the available wording is incomplete. The complete cohort definition, the number analyzed, and handling of protocol deviations are not reported in the registry record.
In general, an analysis population determines which participants contribute to an estimate. An according-to-protocol population can exclude participants who do not meet specified criteria, while another analysis set may follow different rules. These choices can affect interpretation, especially if inclusion depends on events after randomization. The record does not provide enough detail to assess the consequences of the stated cohort definition.
What does the planning illustration represent?
The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not results from an analysis of participants, and they should not be read as observed power. The numerical planning outputs and the effect fraction are not reported in the registry record.
In general, a sample-size calculation asks how much information a future study might need under chosen assumptions. Its output depends on the assumed effect, variability, allocation, significance level, and desired power. Changing an assumption can change the planning estimate. A calculation based on an observed effect is especially dependent on how that effect was estimated; it does not show that the same effect will occur in a new study. The registry record does not report the trial’s own sample-size justification or the assumptions used in its original design.
For time-to-event planning, the record describes total events as the planning quantity, using the Schoenfeld approach; other planning results are described as participants per arm. No time-to-event primary endpoint is identified in the listed primary outcome. No resulting planning values are available in the registry record for interpretation.
What is not available for statistical interpretation?
The registry lists 104 outcome measures and 0 analyses. It does not report the numerical primary endpoint results, endpoint-specific analysis counts, uncertainty intervals, or inferential tests. The statistical analysis plan, missing-data procedures, multiplicity procedures, and interim-analysis details are not reported in the registry record. Without these details, it is not possible to reconstruct the intended analysis or verify how individual outcome results would have been interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 104 outcome measures, including a panel of cytokines and chemokines and secondary outcomes spanning antibody concentrations and safety or symptom categories. Testing or estimating many outcomes can raise multiplicity concerns. In general, when multiple hypotheses are examined, the chance of at least one apparently notable result can increase if no adjustment or interpretation strategy is used. The registry record does not report whether any multiplicity adjustment, hierarchy, or other strategy was planned.
The registry reports 0 analyses. It therefore does not provide numerical estimates for the listed immune outcomes, tests, confidence intervals, or results of any multiplicity procedure. A statistical plan describing primary and secondary hypotheses, decision rules, or treatment of exploratory endpoints is not reported in the registry record. The outcome listings alone do not reveal which findings, if any, were intended to be confirmatory.
The primary outcome description refers to an According-To-Protocol cohort for innate immunogenicity through Day 60 in Step 1. It gives a general inclusion description, but the available wording is incomplete. The number analyzed for each marker, the reasons participants might be excluded, and the handling of missing measurements are not reported in the registry record.
In general, missing measurements can affect estimates if the participants with observed data differ from those without data. The impact depends on how much information is missing, why it is missing, and the analysis approach. None of those details can be assessed for the primary endpoint from the registry record. The record also does not report whether analyses used an imputation method, a complete-case approach, or another procedure.
These omissions limit interpretation of precision and representativeness. They do not establish that particular analyses or procedures were absent from the conduct of the study; they indicate that the registry record does not report them.
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 |
|---|---|---|---|
| HBsAg/AS_1+2 Group | 0 | 38 | 0.0% |
| Engerix-B_1+2 Group | 1 | 40 | 2.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HBsAg/AS_1+2 Group | 0 of 38 |
| Engerix-B_1+2 Group | 0 of 40 |
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 |
|---|---|
| HBsAg/AS_1+2 Group | 16 of 38 |
| Engerix-B_1+2 Group | 13 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | HBsAg/AS_1+2 Group | Engerix-B_1+2 Group |
|---|---|---|---|
| Cholecystitis | Hepatobiliary disorders | 0 of 38 | 1 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HBsAg/AS_1+2 Group | Engerix-B_1+2 Group |
|---|---|---|---|
| Headache | Nervous system disorders | 2 of 38 | 5 of 40 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 6 of 38 | 1 of 40 |
| Nasopharyngitis | Infections and infestations | 5 of 38 | 1 of 40 |
| Back pain | Musculoskeletal and connective tissue disorders | 3 of 38 | 0 of 40 |
| Dysmenorrhoea | Reproductive system and breast disorders | 0 of 38 | 3 of 40 |
| Oral herpes | Infections and infestations | 2 of 38 | 1 of 40 |
| Fatigue | General disorders | 0 of 38 | 2 of 40 |
| Influenza like illness | General disorders | 2 of 38 | 0 of 40 |
| Migraine | Nervous system disorders | 0 of 38 | 2 of 40 |
| Toothache | Gastrointestinal disorders | 0 of 38 | 2 of 40 |
Serious events with the highest arm-level rate: cholecystitis (2.5%).
The registry reports serious-adverse-event figures for the HBsAg/AS 1+2 Group and the Engerix-B 1+2 Group. The number at risk for serious adverse events was 38 in the HBsAg/AS 1+2 Group, with 0 affected, and 40 in the Engerix-B 1+2 Group, with 1 affected. Deaths were recorded as 0 in each group. These are the counts recorded; they do not by themselves establish a comparative safety effect.
The registry lists Cholecystitis at 2.5% as the top serious term. The record excerpt does not identify the group for that term or provide further event-level context. The timing, duration of follow-up for these safety counts, event definitions, and details of relatedness are not reported in the registry record. The recorded count should therefore be read alongside those limitations.
In general, safety counts describe events observed and recorded in a defined group during a stated observation period. A count does not describe the severity or clinical course of every event, and a comparison between groups requires attention to follow-up, exposure, and the way events were collected. Those details are not reported in the registry record. The listed counts are descriptive and should not be treated as proof that an event risk is absent or that the groups differ.
12. What the Result Does, and Does Not, Mean
The registry record supports a description of the study design, vaccine schedules, endpoint definition, and selected serious-adverse-event counts. It does not report numerical results for the primary cytokine and chemokine endpoint. Consequently, it cannot show the measured baseline concentrations, their variability, or a difference between the randomized groups for that endpoint.
The primary endpoint was measured at Day -30, before placebo administration. This timing is important: baseline values do not quantify a response to the later vaccine schedules. The study’s stated aim was to develop immune read-outs and characterize early and adaptive responses, but the registry record does not report numerical evidence about whether the listed markers changed over time or differentiated the groups.
The registry lists 104 outcome measures and 0 analyses. The outcome names indicate areas the study intended to assess, including antibody concentrations, symptoms, and adverse events. Except for the limited safety counts, numerical results for these outcomes are not reported in the registry record. An outcome’s inclusion in the record is not evidence of a particular finding.
In general, an estimate and its uncertainty are both needed to judge how precisely a result is known. A difference observed in data may be compatible with a range of values, and the width of a confidence interval conveys information about that uncertainty. No primary-endpoint estimates or confidence intervals are reported, so neither magnitude nor precision can be judged.
The safety figures show 0 serious adverse events recorded in the HBsAg/AS 1+2 Group and 1 in the Engerix-B 1+2 Group, with 0 deaths recorded in each group. These counts are descriptive. The registry information does not establish a causal explanation for an event or a comparative safety conclusion.
Overall, the record is informative about what was planned and which outcomes were registered, but it does not provide the numerical primary results needed to assess immune-marker findings. It cannot establish that either schedule produced a particular immune response or that one schedule differed from the other.
13. Why This Trial Matters Statistically
This study is statistically notable for its emphasis on developing measurements of immune response rather than presenting a single clinical efficacy comparison in the registry record. Its stated purpose was to develop immunological read-outs and technologies for characterizing early response, response kinetics, and adaptive responses to adjuvanted vaccines. That goal makes measurement definition and timing central to interpretation.
The primary endpoint is a panel of plasma cytokine and chemokine concentrations summarized by medians and inter-quartile ranges. This highlights an important statistical distinction: describing a marker’s distribution is not the same as estimating a treatment effect. A baseline summary can characterize measurements at a point in time, while a claim about change or a difference between schedules requires appropriately timed measurements and a defined comparison. The registered primary time point, Day -30 before placebo administration, is baseline rather than a post-vaccination measurement.
The study also illustrates why a large outcome listing does not itself provide evidence of a result. The registry lists 104 outcome measures but 0 analyses. Without numerical estimates, uncertainty intervals, and analysis details, readers cannot judge the magnitude, precision, or consistency of findings across outcomes. Multiplicity and missing-data methods are also not reported in the registry record.
In general, exploratory immune markers may require careful interpretation because measurement, variability, timing, and analysis choices all affect what can be concluded. This is a general statistical point, not a finding that any particular marker in this study was exploratory or unreliable. The available record supports understanding the research aim and design, while leaving the actual primary-endpoint results unreported.
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 this trial from the registry record is that numerical results for the primary endpoint are not reported. Although the record specifies a panel of plasma cytokines and chemokines, the measurement time, units, and summary statistics, it does not give the observed concentrations, inter-quartile ranges, or comparisons between groups. The magnitude and precision of the primary findings therefore cannot be assessed.
The primary measurement time was Day -30, before placebo administration. This defines a baseline measurement, but the registry record does not provide later numerical measurements or estimates of change. The study’s stated aim includes characterizing early and adaptive immune responses, yet the available outcome information does not permit assessment of response kinetics.
The primary endpoint population description refers to an ATP cohort through Day 60 in Step 1, but its wording is incomplete. Endpoint-specific numbers analyzed, missing-data handling, protocol-deviation rules, and reasons for exclusion are not reported in the registry record. The statistical analysis plan, multiplicity strategy, and interim-analysis details are also not reported.
For safety, the registry provides limited counts, but further event context and the observation period for these figures are not reported in the registry record. The listed serious-event term is not accompanied by group attribution in the available information. These limits constrain interpretation of the safety counts.
Finally, the registry lists 104 outcome measures and 0 analyses. This leaves a substantial gap between the breadth of registered outcomes and the numerical results available for interpretation. The design and objectives can be described, but conclusions about immune-marker differences, changes over time, or comparative outcomes cannot be drawn from the reported information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Development of Read-outs in Healthy, Hepatitis B Virus Naive Adults Vaccinated With the Hepatitis B Surface Antigen (HBsAg) in Combination With a GlaxoSmithKline (GSK) Biologicals' Adjuvant System — NCT01777295.
- Registry record last updated 2019-01-04; status last verified 2018-06.
- Results first posted 2019-01-04.
- 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.
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18. Record Summary
NCT01777295 was a completed, randomized, single-masked, parallel Phase 2 study sponsored by GlaxoSmithKline, with an enrollment of 81. It enrolled healthy adults naive to hepatitis B virus and investigated immune read-outs and reactogenicity.
The HBsAg/AS group received placebo at Day -30 followed by vaccine doses at Day 0 and Day 30. The Engerix-B group received placebo at Day -30 followed by doses at Day 0, Day 30 and Day 180. The primary endpoint was plasma cytokine and chemokine concentrations at Day -30, summarized as medians and inter-quartile ranges.
The registry lists 104 outcome measures and 0 analyses. Numerical primary-endpoint results are not reported in the registry record. Serious-adverse-event counts were 0 in the HBsAg/AS 1+2 Group and 1 in the Engerix-B 1+2 Group; deaths were recorded as 0 in both groups.