Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 (NCT01999231), a randomized phase 1 study. The primary outcome is the Cases of Adverse Events With Participant Injection of ESAT6-CFP10.

2. Clinical Question

3. Trial Design

This is a Phase I clinical tolerability study of recombinant Mycobacterium tuberculosis allergen ESAT6-CFP10 in healthy adults. The registry record lists its status as completed, its allocation as randomized, its masking as none, and its model as single group. Four concentration groups are listed: 1μg/ml, 5μg/ml, 10μg/ml, and 20μg/ml. Each arm description specifies a 0.1ml intradermal injection into the right or left forearm, according to a randomisation scheme. No separate placebo or standard-care arm is described.

The enrollment field reports 32 participants. In contrast, the brief summary says 24 healthy adults were included and describes four groups of 6 people per dose. The posted arm results list 6.0 participants in each group. The registry record does not explain how the enrollment figure relates to the group descriptions or posted arm counts, so these figures should not be treated as interchangeable without clarification.

The brief summary describes assessment of vital signs at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, and 96h after injection; skin reactions and local symptoms; adverse events; and laboratory and other examinations before injection and 7 days after injection. The primary outcome gives an adverse-event timeframe of within 7 days after injections. The study start is listed as 2013-09 and primary completion as 2013-10. The record does not report the randomization procedure, allocation concealment, eligibility criteria beyond healthy status, or a detailed protocol.

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: ESAT6-CFP10 allergen similar to TB-PPD(Tuberculin purified protein derivative ), main ingredients are protein and can cause specific skin allergy in the injection site ( such as redness, swelling, induration, blisters), besides other local reactions, is still listed as adverse events .

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Aged from 18 to 40 years old, the male to female ratio of cases is 1:1 in each group . Body mass index should be in the range of 20 to 27 .

6. Primary Endpoint

The registry lists the primary outcome as the Cases of Adverse Events With Participant Injection of ESAT6-CFP10, measured over within 7 days after the injections.

The primary endpoint is titled as the cases of adverse events with participant injection of ESAT6-CFP10, with a unit of cases and a timeframe of within 7 days after the injections. It is a count outcome: it records the number of adverse-event cases, rather than a mean measurement or a time-to-event estimate. The record describes local skin reactions, including redness, swelling, induration, or blisters, as possible adverse events, alongside other local reactions and events.

A count of adverse events can describe the safety observations made during a short tolerability study. It is relevant to an early-phase study because the stated purpose is preliminary evaluation of safety and tolerability in humans. The endpoint should nevertheless be read according to what it measures: cases recorded during a defined follow-up period. It does not by itself describe severity, duration, causality, or the number of distinct participants affected. Those details are not fully reported in the registry record.

The posted primary counts are 3.0 cases in the 1μg/ml group, 1.0 in the 5μg/ml group, and 0.0 in each of the 10μg/ml and 20μg/ml groups. These are descriptive counts from small groups, not estimates of comparative treatment effects. The registry does not report confidence intervals, a formal statistical test, or an analysis plan for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint mean?

A count endpoint records how many events occurred, rather than the average value of a continuous measurement. Here, the primary outcome is the number of adverse-event cases within 7 days after injections. Counts can be useful when the events themselves are the subject of interest, but interpretation depends on whether the count refers to events or people. One participant may potentially contribute more than one case, whereas a participant count records whether people were affected. The primary endpoint is expressed as cases; the separate adverse-event summary reports participants affected. The registry record does not explain the relationship between these measures.

How should the four dose groups be compared?

The study lists four dose groups and labels the model single group. Randomized allocation is also reported, but no separate comparator arm is described. A numerical difference in counts between dose groups is descriptive unless a suitable analysis accounts for the design and uncertainty. The posted registry record reports no analyses, confidence intervals, or statistical test. It therefore does not establish whether the observed count pattern is compatible with chance variation, a dose-related pattern, or other explanations. A count of zero in a small group should not be interpreted as proof that the event cannot occur at that concentration.

Why does uncertainty matter?

General statistical explanation: a confidence interval describes a range of values compatible with the observed data under a specified method and assumptions. It communicates precision, which is especially important when event counts and group sizes are small. The record does not report confidence intervals for the adverse-event counts. Without such estimates, readers cannot use the posted results to quantify how uncertain an underlying event frequency may be. A formal comparison would also need to account for the outcome definition, follow-up, and group structure.

Why can event data be over-dispersed?

General statistical explanation: count data are sometimes more variable than a simple statistical model expects. This is called over-dispersion. It can arise when events cluster among participants or when people differ in their underlying event rates. If over-dispersion is present and not accounted for, standard errors may be too small and confidence intervals too narrow. Whether over-dispersion is relevant depends on the data and model; the registry record does not report a count model, an over-dispersion assessment, or analyses from which to evaluate it.

What can be inferred from the posted analyses?

The record lists zero analyses. It gives the primary counts by arm, but no inferential statistical plan, adjusted or unadjusted comparison, model, or handling of repeated events. It is not reported in the registry record whether analyses were planned at the participant level, event level, or both. General statistical explanation: when a trial includes multiple outcomes or comparisons, prespecifying the primary analysis helps distinguish planned questions from exploratory ones. The protocol and analysis plan are not reported in the registry record, so the intended inferential framework cannot be described.

The record also does not report sample-size justification. The listed group sizes and event counts describe the study as recorded; they do not reveal what effect size the trial was designed to detect or how precisely it could estimate event rates. Any sample-size illustration elsewhere should be treated as a planning exercise based on stated assumptions, not as observed power or evidence that the study was adequately powered. General statistical explanation: observed power calculated from an observed result does not resolve uncertainty; estimates and confidence intervals are more informative for interpreting precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary adverse-event endpoint and five secondary outcomes concerning the number of participants with induration and/or redness at 2h, 24h, 48h, 72h, and 96h after application. The record reports no analyses for these outcomes. It does not describe a prespecified statistical plan, a method for controlling the chance of false-positive findings across multiple outcomes, or a hierarchy among secondary questions. General statistical explanation: examining multiple outcomes or time points can increase the chance of finding a nominally unusual result by chance, so interpretation depends on whether analyses were planned and how multiplicity was handled. Those details are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The record does not state whether all enrolled participants completed every follow-up assessment, how missing observations were handled, or whether the analysis population differed from the enrolled population. The enrollment field reports 32, while the brief summary describes 24 adults and four groups of 6, and the posted arm results list 6.0 per group. The record does not explain the relationship among these figures. That uncertainty makes it difficult to determine the denominator used for every outcome or whether any participants lacked outcome data.

The registry record does not define analysis populations such as all randomized participants or participants who completed follow-up. It also does not report a participant flow account. Without these details, the posted counts can be described as reported results, but their completeness and the handling of missing observations cannot be independently assessed from the record.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event summary reports 0 affected participants in each of the four dose groups. The group summaries list 6 participants at risk in each group. This means that no serious adverse events are recorded in the posted summary for the stated groups; it does not establish that the true risk is zero or rule out events that were not observed during the study.

The same summary separately reports other adverse events affecting 2 participants in the 1μg/ml group, 1 participant in the 5μg/ml group, and 0 participants in each of the 10μg/ml and 20μg/ml groups. These are participant counts for other adverse events, not counts of all adverse-event cases. The primary endpoint reports cases, with 3.0, 1.0, 0.0, and 0.0 across the corresponding groups. The registry record does not explain how cases map to affected participants, so the measures should not be treated as equivalent.

The posted summary does not provide event descriptions, severity grades, timing by event, or individual-level narratives. The serious-event figures should therefore be read narrowly as the reported participant counts, not as a comprehensive characterization of safety or a comparison among doses.

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

The registry record describes an early-phase study of intradermal ESAT6-CFP10 in healthy adults, with four dose groups and short-term safety and tolerability assessment. The primary outcome counts adverse-event cases within 7 days after injection. The posted counts are 3.0 in the 1μg/ml group, 1.0 in the 5μg/ml group, and 0.0 in each of the 10μg/ml and 20μg/ml groups. The separate adverse-event summary reports no serious adverse events affecting participants in any group, and other adverse events affecting 2, 1, 0, and 0 participants, respectively.

These findings describe the events recorded in the registry. They do not establish a causal relationship, a dose-response pattern, or a comparative safety difference. The groups are small, the record contains no uncertainty estimates or statistical analyses, and a zero observed count does not imply zero underlying risk. The endpoint also distinguishes cases from participants, and the relationship between those counts is not explained.

The results do not establish longer-term safety, effects in populations other than healthy adults, or outcomes beyond the recorded follow-up. The registry's brief summary describes examinations before injection and 7 days after injection, while the primary endpoint specifies events within 7 days. The record does not provide detailed results for every examination or follow-up assessment. It also does not report a protocol or statistical analysis plan.

The enrollment field and brief summary give different enrollment descriptions: 32 in the enrollment field, compared with 24 in the summary, which also describes four groups of 6. The posted arm results list 6.0 participants per group. Because the record does not reconcile these figures, interpretation should not assume a single enrollment total beyond the individual entries. The results are best understood as limited descriptive evidence from a small, short-term Phase I study, rather than as a definitive estimate of the frequency or comparative distribution of adverse events.

13. Why This Trial Matters Statistically

This study illustrates an important statistical feature of early-phase safety research: the first objective may be to characterize observed events and tolerability, rather than to estimate a precise comparative effect. The record describes a short follow-up period and four dose groups, with the primary endpoint expressed as adverse-event cases. Such counts can provide a basic account of what was recorded, but small groups and sparse events place limits on the precision of any broader inference.

The distinction between event counts and participant counts matters. The primary endpoint reports cases, while the separate safety summary reports participants affected by serious and other adverse events. Without detail on how repeated events were counted or linked to participants, the measures answer different descriptive questions. This is a general lesson for clinical-trial reporting: endpoint definitions and denominators need to be explicit for readers to interpret counts consistently.

The registry also demonstrates why design and analysis details matter alongside numerical results. It identifies randomized allocation and a single-group model, but does not describe a separate comparator or report analyses. The record does not provide the statistical plan, sample-size justification, missing-data handling, or confidence intervals. As a result, the counts can be read directly, but their uncertainty and the intended inferential comparisons remain unclear.

Finally, the enrollment figures are not reconciled: the enrollment field reports 32, while the brief summary describes 24 participants and four groups of 6, and the posted arm results list 6.0 per group. Explicitly documenting participant flow and the analysis population would help readers understand the basis of each result. These reporting issues are relevant to interpretation without changing the narrow descriptive meaning of the observed counts.

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 posted results are limited by the small group sizes and sparse adverse-event counts. Each arm is listed with 6.0 participants, and two groups have 0.0 cases for the primary endpoint. The record provides no confidence intervals or inferential analyses, so precision and comparative uncertainty cannot be assessed from the reported results.

The enrollment information is not internally reconciled. The enrollment field reports 32, whereas the brief summary describes 24 participants divided into four groups of 6; the posted arm results list 6.0 in each group. The registry record does not explain these figures or specify the analysis population. This leaves uncertainty about how the overall enrollment entry relates to the reported arm data.

The primary endpoint counts cases, while the safety summary counts participants affected. Event-level detail is not reported, so the correspondence between the two summaries is unclear. The record also does not provide event severity, descriptions, onset, duration, or participant-level information. Although the brief summary describes several assessments, detailed results for those examinations are not presented in the posted primary outcome information.

The record lists five secondary skin-reaction outcomes but reports no analyses. Statistical methods, missing-data handling, multiplicity procedures, randomization details, and sample-size justification are not reported in the registry record. Follow-up for the primary endpoint is within 7 days, so the reported results do not characterize longer-term events. These limitations restrict interpretation to the descriptive results and study details recorded, without supporting precise estimates or conclusions about dose differences.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 — NCT01999231.
• Registry record last updated 2015-03-31; status last verified 2015-03.
• Results first posted 2015-03-31.
• 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

The registry record describes a completed Phase I study of intradermal ESAT6-CFP10 in healthy adults, with randomized allocation, no masking, and a single-group model. Four concentrations are listed: 1μg/ml, 5μg/ml, 10μg/ml, and 20μg/ml. The primary endpoint is adverse-event cases within 7 days after injections.

Posted primary counts are 3.0, 1.0, 0.0, and 0.0 across the four groups, respectively. The serious adverse-event summary lists 0 affected participants in each group. Other adverse events are reported for 2, 1, 0, and 0 participants, respectively. The record lists five secondary skin-reaction outcomes but no analyses.

The enrollment field reports 32, while the brief summary describes 24 participants and four groups of 6; posted arm results list 6.0 per group. The record does not reconcile these figures or report confidence intervals, a statistical analysis plan, or missing-data methods. The results therefore support a descriptive account of the recorded short-term counts, not a precise comparison among doses.