Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine (NCT02639351), a randomized phase 1 study. The primary outcome is Number of Subjects With Any Solicited Local and Systemic Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, observer-blind, parallel-group, dosage-escalation study. It compared four LHD153R-adjuvanted MenC-CRM formulations with a MenC-CRM comparator in healthy adults aged 18 to 45 years. The registry lists an enrollment of 80 participants. The adverse-event groups each include 16 participants: four LHD153R formulation groups and one MenC group.

Participants received a single dose. The four investigational formulations contained 12.5 ug, 25 ug, 50 ug, or 100 ug of LHD153R. The comparator was MenC-CRM; the official title describes it as aluminium hydroxide-adjuvanted MenC-CRM. The study was designed to evaluate safety and immunogenicity. Secondary outcomes included hSBA antibody measures against MenC, seroresponse, ELISA antibody concentrations, and the proportion with at least a 4-fold increase in ELISA antibody concentrations.

The registry records the study as completed. Its listed start date is 2016-03-01 and its primary completion date is 2017-08-31. The sponsor is GlaxoSmithKline. Allocation concealment details, the randomization method, and any procedures used to maintain observer blinding are not reported in the registry record. The record also does not describe how the dosage escalation was operationalized, such as whether later groups could proceed only after review of earlier safety data.

This design can describe safety and immune-response observations in the enrolled groups. It does not, by design alone, establish that observed differences are causal or precisely estimated. The groups are small, and a detailed statistical analysis plan is not reported in the registry record. The exact rationale for the enrollment target and the planned comparisons among the four doses and comparator are also not reported.

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

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the Solicited Safety Set which included all enrolled subjects who received a study vaccination and reported solicited local and systemic symptoms.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Any Solicited Local and Systemic Adverse Events (AEs), measured over Within 30 minutes of vaccination (Min) at Day 1.

The primary endpoint is the number of participants with any solicited local or systemic adverse event within 30 minutes of vaccination on Day 1. It focuses on symptoms assessed shortly after vaccination, rather than on all possible adverse events during an unspecified follow-up period. The registry defines local symptoms as injection-site erythema, induration, pain, and swelling. Erythema, induration, or swelling counted when spreading beyond 25 millimeters from the injection site; any occurrence of pain counted regardless of intensity grade.

The solicited systemic symptoms were arthralgia, chills, diarrhea, fatigue, fever, headache, loss of appetite, myalgia, nausea, rash, urticaria, and vomiting. Fever was defined as oral body temperature greater than or equal to 38 degrees Celsius. Any systemic symptom counted regardless of intensity grade. The endpoint combines these local and systemic events into a participant-level count, so it concerns whether a participant experienced at least one listed symptom in the stated window.

Solicited endpoints are used in vaccine safety assessment to collect information about specified symptoms in a consistent way. General explanation: defining symptoms and a collection window can make safety reporting more structured, but a composite endpoint does not show which symptom occurred unless the component results are reported separately. The registry describes the endpoint and analysis population, but the primary endpoint’s group-specific counts and comparison are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General explanation: a randomized parallel-group design assigns participants to separate treatment groups and compares outcomes across those groups. Randomization is intended to make treatment assignment independent of participants’ characteristics, on average, but the method used to generate or conceal assignments is not reported in the registry record. The study is described as observer-blind. The record does not specify who remained unaware of assignment or how blinding was maintained.

What does the primary endpoint count?

The primary measure is a participant count: whether each participant experienced any solicited local or systemic symptom in the specified post-vaccination window. This type of binary outcome reduces multiple symptom observations to a yes-or-no status for each participant. That can give a concise summary, but it does not retain the full detail of symptom type, intensity, duration, or recurrence. The registry’s definition says that any occurrence of pain and any occurrence of a listed systemic symptom counted regardless of intensity grade. For specified local signs, the registry gives a size threshold.

The reported primary outcome timeframe is within 30 minutes of vaccination on Day 1. The endpoint’s stated window is therefore narrow. It should not be interpreted as a summary of all symptoms arising after vaccination over the full study period. The registry lists other adverse-event information separately, but the relationship between those summaries and the primary solicited endpoint is not stated as a single comparative analysis.

How should a group comparison be understood?

General explanation: for a binary outcome, a comparison might describe the event frequency in each group and an effect measure such as a difference or ratio, with a confidence interval to convey uncertainty. A confidence interval represents a range of values compatible with the data and the method’s assumptions; it is not a guarantee that the true effect lies within that range. No primary-endpoint effect estimate, confidence interval, or p-value is reported in the registry record. A new comparison should not be inferred from the safety summaries because the primary outcome was not reduced to one comparison.

The registry identifies 68 outcome measures and reports no analysis entries. It lists hSBA geometric mean titers, geometric mean ratios, seroresponse, ELISA antibody concentrations, and the proportion with at least a 4-fold increase among the secondary outcomes. These outcomes use different scales and definitions. General explanation: continuous antibody measures and binary response outcomes require summaries suited to their data types. A geometric mean summarizes values on a multiplicative scale, while a participant count or percentage describes how many participants meet a specified event definition. The record does not provide outcome-specific estimates or methods for these measures in the registry record.

What is the role of the planning illustration?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The assumptions also specify that non-time-to-event outputs are participants per arm, while time-to-event outputs would count total events. No numerical planning results or observed effect values are reported in the registry record. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect.

General explanation: sample-size calculations depend on assumptions about the effect size, outcome variability or event frequency, significance threshold, allocation, and analysis method. Changing an assumed effect changes the number of observations needed to detect it under the model. An illustration based on an observed effect is especially dependent on that estimate, which can be unstable in a small study. The registry does not report the trial’s own sample-size justification, and the posted assumptions should not be presented as the protocol’s original design basis.

What can be inferred from the serious-event counts?

General explanation: sparse event counts provide limited information about the range of plausible event rates. A zero count is an observation in the study group, not proof that an event cannot occur. A count of one is also subject to substantial uncertainty when the group is small. To assess the precision of a rate or a difference, an analysis would ordinarily report an uncertainty measure and clarify the observation period and event definitions. The registry’s serious-event counts do not include a reported confidence interval or comparative test.

The top serious term Joint injury is listed at 6.2%, but the term listing does not state its group or denominator. It should not be assigned to a particular formulation or used to reconstruct an event rate. The group summaries separately report serious-event counts and deaths, which can be described directly without extrapolating to unobserved participants or follow-up.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 68 outcome measures, including multiple immunogenicity outcomes and safety measures. A study with multiple outcomes or comparisons can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. General explanation: statistical plans may address this through a hierarchy of outcomes, adjusted significance thresholds, or clearly exploratory interpretation. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or which comparisons were intended as confirmatory.

The record reports no analysis entries. It does not give a primary-endpoint comparative result, a detailed analysis plan, or a description of any adjustment for multiple testing. It is therefore not possible to determine from the registry record whether the listed outcome analyses were prespecified, how they were conducted, or how their results were intended to be interpreted together.

The primary analysis population is described as the Solicited Safety Set, including enrolled subjects who received a study vaccination and reported solicited local and systemic symptoms. The registry does not report the number excluded from this set, the handling of participants with incomplete symptom records, or how missing observations were treated. It also does not state whether analyses used additional populations for immunogenicity or other safety outcomes. These details matter because the analyzed participants and missing-data method can affect the estimates and their interpretation.

General explanation: missing outcomes can reduce precision, and estimates may be biased if the probability of missingness is related to symptoms or treatment group. The registry does not describe checks or sensitivity analyses addressing that possibility. The specific rationale for enrollment and the statistical procedures for the reported outcomes are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: joint injury (6.2%).

The serious adverse-event summaries list 16 participants at risk in each group. There were 0 serious adverse events in each of the four LHD153R formulation groups and 1 in the MenC group. Deaths were reported as 0 in all five groups. These are counts in the study groups, not estimates of the frequency of all possible harms beyond the participants and observation represented in the registry.

The registry also lists Joint injury at 6.2% among the top serious terms. The term listing does not identify a group or denominator, so it cannot be attributed to a particular arm from the registry record. The listed serious-event figures should not be conflated with the primary endpoint, which counts solicited local and systemic symptoms within 30 minutes of vaccination on Day 1.

General explanation: serious events are typically uncommon, and small group sizes make their rates difficult to estimate precisely. A zero count does not establish zero risk, while one event does not by itself establish a group difference. The registry does not report confidence intervals or a statistical comparison for the serious-event counts. These data support a description of what was recorded, not a conclusion that one vaccine formulation has a different safety profile.

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

The study addresses an early-stage safety and immunogenicity question in healthy adults aged 18 to 45 years. It compares four single-dose LHD153R-adjuvanted MenC-CRM formulations, spanning 12.5 ug to 100 ug, with a MenC-CRM comparator. The registry reports 80 participants overall, distributed as 16 in each of the five groups in the adverse-event summaries. This is a description of a small phase 1 study, not evidence from a large effectiveness trial.

The serious-event counts report 0 in each adjuvanted group and 1 in the comparator group, with 0 deaths in every group. These figures describe the observations recorded in those participants. They do not show that the underlying risk is absent in groups with no recorded events, or that the observed difference in counts reflects a true difference between formulations. No confidence intervals or comparative tests for these counts are reported.

The primary endpoint was designed to count participants with any solicited local or systemic symptoms within 30 minutes on Day 1. Although its symptom definitions and analysis population are described, a group-by-group primary endpoint result is not reported. The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The broader adverse-event summaries cannot substitute for the missing primary-endpoint comparison.

The registry identifies immunogenicity outcomes, but the outcome-specific results are not reported in the registry record for this interpretation. The listed outcomes alone do not establish the magnitude or precision of an antibody response. Nor does a sample-size planning illustration establish observed power; it describes assumptions for planning and is not a probability that the study detected a true effect.

Accordingly, the posted record permits a description of the design, outcome definitions, group sizes, and reported serious-event counts. It does not support a definitive comparative conclusion about safety or immunogenicity. The absence of detailed analysis results, uncertainty estimates, multiplicity procedures, and missing-data methods limits how strongly the observations can be interpreted.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the challenges of interpreting early-phase, multi-arm vaccine studies. Four investigational formulations were compared with a single comparator, with 16 participants listed in each group. Such a layout can support descriptive assessment across dose formulations, but the small group counts limit the precision with which uncommon events or between-group differences can be characterized.

The primary endpoint is a composite participant-level measure. It brings several local and systemic symptoms together, while the registry also defines distinct components and a specific assessment window. This makes clear why knowing the endpoint definition is essential: a count of participants with any symptom answers a different question from counts for each symptom, severity, or events over a longer period. The registry does not report a single result for this primary measure.

The study also illustrates the importance of separating observed safety counts from inferential conclusions. The serious-event summaries report zero in the four LHD153R groups and one in the comparator group, but do not include uncertainty estimates or a comparative test. General explanation: event counts in small groups can be compatible with a range of underlying rates, so the raw counts alone are not a reliable basis for ranking groups.

Finally, the record lists many outcome measures and does not report a detailed statistical analysis plan or multiplicity approach. That matters because the interpretation of multiple immune-response and safety outcomes depends on which questions were prespecified and how comparisons were handled. The record is useful for identifying the study’s design and planned outcome domains, while the limited outcome analyses available constrain conclusions about comparative effects.

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 the registry record does not report a group-specific result or comparative estimate for the solicited local and systemic endpoint. The outcome is defined as any listed symptom within 30 minutes of vaccination on Day 1, but the posted adverse-event group summaries do not provide that endpoint as a single comparison. As a result, the primary safety question cannot be answered from the reported counts alone.

The study included 80 participants, with 16 listed in each adverse-event group. These group sizes limit precision, particularly for uncommon outcomes. The serious-event summary reports 0 in four groups and 1 in the MenC group, but does not provide confidence intervals or comparative tests. The Joint injury term is listed at 6.2% without a group or denominator, preventing a group-specific interpretation of that listing.

The registry lists 68 outcome measures and no analysis entries. It does not report a detailed statistical analysis plan, a multiplicity procedure, or the intended hierarchy of outcomes. Missing-data handling and the number excluded from the stated Solicited Safety Set are also not reported. These omissions make it difficult to assess whether the posted summaries represent all planned analyses or how incomplete reporting could affect interpretation.

The sample-size assumptions are described as a planning illustration based on an observed effect, but numerical planning results and the observed effect are not reported. The trial’s own sample-size justification is not reported in the registry record. The record also does not explain the randomization method, allocation concealment, blinding procedures, or how dose escalation decisions were made. These design details would be relevant when assessing potential bias and the scope of the conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine — NCT02639351.
• Registry record last updated 2019-06-28; status last verified 2019-06.
• Results first posted 2019-06-07.
• 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.

18. Record Summary

NCT02639351 is a completed phase 1 randomized, observer-blind, parallel-group dosage-escalation study sponsored by GlaxoSmithKline. It enrolled 80 healthy adults aged 18 to 45 years and compared single doses of four LHD153R-adjuvanted MenC-CRM formulations with MenC-CRM. The listed LHD153R amounts were 12.5 ug, 25 ug, 50 ug, and 100 ug, with 16 participants in each of the five adverse-event groups.

The primary endpoint was the number of participants with any solicited local or systemic adverse event within 30 minutes of vaccination on Day 1. Its symptom definitions and analysis population are described, but a single comparative primary result is not reported. Serious-event counts were 0 in each LHD153R group and 1 in the MenC group; deaths were 0 in all groups. The registry lists immunogenicity outcomes but does not report their results in the registry record used for this summary. Detailed analysis methods, multiplicity procedures, and missing-data handling are not reported in the registry record.