A Study to Assess Safety, Tolerability and Immunogenicity of the Live Attenuated hRSV Vaccine rBCG-N-hRSV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Safety, Tolerability and Immunogenicity of the Live Attenuated hRSV Vaccine rBCG-N-hRSV (NCT03213405), a randomized phase 1 study. The primary outcome is Number of Subjects With Required Adverse Events Grade II, III, and IV, Laboratory Adverse Events Grade II, III, and IV, and Severe Considered Adverse Events Related to the Vaccine..

2. Clinical Question

3. Trial Design

This was a randomized, controlled, sequential dose-escalation Phase I study. The registry identifies quadruple masking, while the official study title describes the study as double blind and controlled by conventional BCG. The record does not explain how those masking descriptions relate to one another or specify which roles were masked.

The trial enrolled 24 healthy adult males and assigned six participants to each of four groups: conventional BCG full dose, recombinant BCG at 1/100 dose, recombinant BCG at 1/10 dose, and recombinant BCG full dose. Each group received one intradermal injection at study entry. The record identifies the study model as sequential, but the detailed dose-escalation procedures, criteria for moving between doses, and decision authority are not reported in the registry record.

The study's stated aims were to evaluate safety, tolerability, and immunogenicity. The recorded primary outcome is a count of participants with specified adverse events, with follow-up up to 180 days after vaccination; the timeframe also describes the whole study as 11 months and 6 days. The registry lists one outcome measure and no analyses. It does not report immunogenicity results in the information available for this analysis.

The study is marked completed. Its recorded start date is 2017-06-27 and its primary completion date is 2018-06-01. No additional details about recruitment, participant flow, protocol amendments, or the conduct of dose escalation are 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

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 Required Adverse Events Grade II, III, and IV, Laboratory Adverse Events Grade II, III, and IV, and Severe Considered Adverse Events Related to the Vaccine., measured over Up to 180 days post-vaccination (A total of 11 months and 6 days for the whole study).

The primary endpoint counts participants with adverse events meeting the endpoint's specified criteria. It includes required adverse events of grades II, III, and IV; laboratory adverse events of grades II, III, and IV; and severe adverse events considered related to vaccination. The record says required events included pain, induration, pustule, fever, headache, myalgia, and diarrhea, among others. These were collected through diary cards, study visits, and study phone calls. Laboratory events included hematological and biochemical measures such as blood counts, transaminases, cholesterol, creatine phosphokinase, and urine analyses.

The registry defines severe adverse events by serious consequences such as death, a life-threatening event, hospitalization, or disability, among others. Grade 4 laboratory adverse events were also treated as severe adverse events. The endpoint is useful in an early-phase study because event counts can describe the types and frequency of observed safety concerns during the stated follow-up. It is not a single clinical event: it combines different kinds and grades of events, so interpretation depends on the separate event categories and their definitions.

The outcome is recorded as a count of participants, not as a comparative effect estimate. The registry record does not report results for each component of the endpoint, or a single summarized primary-outcome result by group. It therefore does not establish how the groups compare on the full endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome in the sense that each participant either meets a specified event criterion or does not. The registry expresses the outcome as a count of participants. Counts are straightforward to interpret: they state how many participants in a group experienced an event matching the definition. They do not, by themselves, describe how many events each person had, how long each event lasted, or how severe it was beyond the grades included in the endpoint.

In general, a participant-level count differs from an event count. One participant can experience more than one event, and different event categories can overlap. A total across categories cannot be assumed to equal the number of distinct participants unless the record says the categories are mutually exclusive. That detail is not reported in the registry record for this endpoint. The endpoint also brings together clinical symptoms, laboratory findings, and severe events, which have different meanings and ascertainment methods. A single count can therefore conceal meaningful differences in event type.

The endpoint's ascertainment methods include participant diary cards, study visits, and study phone calls for required events. Laboratory adverse events were based on hematological and biochemical parameters. In general, different collection methods may affect when and how an event is detected or recorded. Interpreting the counts benefits from knowing the monitoring schedule, the thresholds used for laboratory grades, and how missing diary entries or missed tests were handled. Those details are not reported in the registry record.

Randomization is intended, in general, to make comparison groups similar on average with respect to factors that could affect outcomes. With six participants in each group, however, randomization cannot ensure that the groups are closely balanced on every characteristic. The record identifies randomized allocation but does not report baseline characteristics or the randomization procedure. The sequential model indicates an ordered dose-escalation design, but the order, escalation rules, and any stopping criteria are not reported. Those details matter because decisions to proceed through dose levels can influence which observations accrue in each group and when they are reviewed.

Masking can reduce the influence of expectations on participant reports, clinical assessments, or other decisions. The registry identifies quadruple masking, while the official title calls the study double blind. The registry does not define the masked roles or clarify the terminology. It is therefore possible to describe the recorded masking labels, but not to assess from the record which participants or study personnel knew the assigned intervention.

For a binary endpoint, a general analysis might compare the proportion of participants with an event in each group, estimate a difference or ratio, and report uncertainty around that estimate. The registry does not report such comparative estimates for the primary outcome. It lists no analyses, and the primary outcome was not reduced to one comparison because it has several categories or time points. No adjustment strategy, model, or inferential method for this endpoint is reported in the registry record.

In general, sparse event data can make estimates unstable and confidence intervals wide. Standard methods may also behave poorly when a group has no observed events; an appropriate analysis depends on the intended estimand and the analysis plan. This is a methodological consideration, not a claim that a particular model was used in this study. No model details or confidence intervals for the primary endpoint are reported.

Multiplicity is a concern in general when many outcomes, categories, time points, or comparisons are examined. The chance of at least one apparently unusual result can rise when many tests are conducted without a planned approach to multiplicity. Here, the recorded endpoint covers multiple event categories and the record does not describe adjustment, outcome hierarchy, or a strategy for interpreting multiple comparisons. It also does not report whether interim analyses were conducted. These omissions prevent a reader from reconstructing a formal testing plan.

The record includes assumptions for planning illustrations: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Such illustrations are not the trial's design justification and do not represent observed power. In general, planning calculations describe hypothetical sample sizes under stated assumptions; they do not establish the probability that the completed study detected an effect. The registry record does not report the original sample-size justification or a formal power calculation for this trial.

Finally, analysis populations can affect results. For example, a protocol may define which randomized participants are included in a primary analysis and how participants who do not complete follow-up are treated. Those definitions, along with missing-data handling and participant disposition, are not reported in the registry record. Without them, the reported counts should be understood as the recorded descriptive counts rather than as results from a fully specified analysis population.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but that measure combines required clinical events, laboratory events, and severe events, and its description includes several categories and grades. The record explicitly does not reduce the primary outcome to one comparison. It does not describe a hierarchy among event categories, define a single summary estimand, or report a multiplicity adjustment. The registry also lists no analyses. As a result, there is no reported confirmatory testing framework from which to interpret a family of primary-outcome comparisons.

Missing-data procedures are not reported in the registry record. The record does not say how missing diary cards, missed visits, unavailable laboratory measurements, or incomplete follow-up were handled. It also does not report the number of participants with evaluable data for each endpoint component or explain whether participants with missing information were excluded from particular counts.

Analysis populations are likewise not specified. The registry record does not state whether the primary endpoint was analyzed among all randomized participants, all vaccinated participants, or another defined group. Although the arm descriptions specify vaccination at study entry and the adverse-event listing gives six participants at risk in each group, the record does not provide a participant-flow account or the analysis rules behind those denominators.

Interim analyses and stopping rules are not reported in the registry record. In a general statistical sense, such details can matter in a sequential dose-escalation study because the timing and use of accumulating safety information affect interpretation. The available record does not allow those procedures to be reconstructed.

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: increase in cpk (16.7%).

The serious adverse-event figures count participants affected, rather than giving a complete inventory of event episodes. The registry records one affected participant among the six in the conventional BCG full-dose group, and zero affected participants among the six in each recombinant BCG group. It records zero deaths in all four groups. These are descriptive counts from the study; they are not, by themselves, a comparative estimate of the chance of a serious event.

Increase in CPK is listed as a top serious adverse-event term at 16.7%. The registry does not provide the term's arm-specific distribution or enough detail to connect it to an individual group count. It also does not report the event's timing, duration, grade, or participant-level context in the information available for this analysis.

The serious-event definition includes death, life-threatening events, hospitalization, or disability, among other criteria, and grade 4 laboratory events were also treated as serious. An event can meet a seriousness criterion without being common, and a count of zero in a small group does not establish that the underlying risk is zero. In general, rare events are difficult to characterize precisely in small studies. The record's counts should therefore be read as observations within this trial, not as a definitive comparison of safety across the interventions.

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

The registry record documents a randomized Phase I study of three doses of recombinant BCG expressing RSV nucleoprotein and a conventional BCG control in healthy adult males. The recorded safety information includes serious adverse-event counts, a top serious-event term, and counts for other adverse events. Those data describe what was recorded in this study during the stated follow-up; they do not provide a full comparative analysis of the primary endpoint.

The serious-event counts are small, with one affected participant in the conventional BCG group and none in the recombinant-vaccine groups. No deaths are recorded. Because there are six participants per group, these observations cannot precisely characterize uncommon events or establish equivalence between groups. A zero count means no event was recorded in that group in this study, not that such an event cannot occur.

The primary endpoint includes several kinds of adverse events and grades, but the registry does not report all component results or a combined comparison. There are no listed analyses, confidence intervals, or p-values for that endpoint. Consequently, the record does not support a formal claim that one group had a higher or lower rate on the full primary endpoint. The listed counts should not be interpreted as evidence that any intervention works or does not work.

The study's stated aims also include tolerability and immunogenicity, but results for those aims are not reported in the registry record available for this analysis. The record does not include the original sample-size justification, detailed analysis populations, missing-data methods, or dose-escalation rules. These gaps limit both statistical interpretation and the ability to reproduce the study's analysis.

In general, early-phase studies can provide descriptive information that helps characterize outcomes and inform further research, but their conclusions depend on the design, outcome definitions, follow-up, and completeness of reporting. Here, the most defensible reading is limited to the recorded counts and the stated study design. Broader claims require information and analyses not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for combining a sequential dose-escalation design with a randomized comparison across three recombinant vaccine doses and a conventional BCG control. That design addresses early-phase questions about safety and tolerability while also identifying immunogenicity as an aim. The record's descriptions make clear that several distinct dose groups were studied, rather than a single intervention against a control.

The primary endpoint illustrates a common challenge in safety reporting: one outcome label may cover different event types, severity grades, collection methods, and follow-up observations. Counting affected participants is interpretable, but a count alone does not preserve the distinctions among symptoms, laboratory findings, and serious events. The registry does not report component-level primary results or a single comparison, leaving the reader without a unified estimate that captures the endpoint as a whole.

The small groups also highlight a general limitation of early-phase safety data. When only a small number of participants are observed, the absence of recorded events in a group provides limited information about uncommon outcomes. Descriptive counts can still be useful for documenting what occurred, but precision and comparative interpretation depend on fuller reporting, including uncertainty estimates and the analysis plan.

The record therefore offers a useful example of why clinical trial interpretation requires more than intervention labels and event totals. Details about outcome definitions, analysis populations, missing observations, masking, dose-escalation decisions, and multiplicity can influence what conclusions are justified. Several of those details are not reported in the registry record, so the statistical reading must remain descriptive and bounded by the information recorded.

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 trial-specific limitation is the small enrollment: 24 participants were divided into four groups of six. Such group sizes provide limited precision for estimates of event frequency, particularly for uncommon serious events. The observed absence of serious events in three groups should not be read as proof that no such events can occur.

The primary outcome combines several categories and grades, yet the registry record does not report a single summarized comparison or results for every component. It lists no analyses. The serious-event counts and other adverse-event counts do not substitute for a complete report of required clinical events and laboratory events under the primary endpoint definition.

The record does not report baseline characteristics, participant flow, missing-data procedures, analysis populations, or the original sample-size justification. It also does not specify the statistical methods used for any outcome, or whether interim analyses were conducted. These omissions make it difficult to assess balance between randomized groups, evaluate completeness of follow-up, or reproduce an analysis.

Specifics of the sequential escalation process are not reported, including the order of dose administration, the rules for dose progression, and any stopping criteria. The masking description is also incomplete: the registry identifies quadruple masking, while the official title says double blind, without defining the roles involved. These design details would help assess how the trial was conducted and how potential sources of bias were addressed.

Finally, the record identifies immunogenicity and tolerability as study aims but does not report their results in the information available for this analysis. The stated adverse-event follow-up is up to 180 days post-vaccination, while the timeframe also describes the whole study as 11 months and 6 days; additional detail on observation schedules is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess Safety, Tolerability and Immunogenicity of the Live Attenuated hRSV Vaccine rBCG-N-hRSV — NCT03213405.
• Registry record last updated 2020-12-11; status last verified 2020-11.
• Results first posted 2020-12-11.
• 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

NCT03213405 is a completed randomized, sequential Phase I study of recombinant BCG expressing human RSV nucleoprotein in healthy males aged 18 to 50 years. The registry records enrollment of 24 participants, six per group, across recombinant BCG doses of 1/100, 1/10, and full dose, and a conventional BCG full-dose control. Each intervention was a single intradermal injection at study entry.

The primary safety outcome counts participants with specified clinical and laboratory adverse events of grades II, III, and IV, as well as severe adverse events considered related to vaccination, with follow-up up to 180 days post-vaccination. Serious-event counts are one participant in the conventional BCG group and zero in each recombinant BCG group; no deaths are recorded. Increase in CPK is listed as a top serious-event term at 16.7%.

The registry lists no analyses and does not report a single comparative result for the multi-category primary outcome. Detailed analysis methods, missing-data procedures, analysis populations, and dose-escalation rules are not reported in the registry record.