Phase 1 Clinical Trial of Single-Vial ID93 + GLA-SE in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1 Clinical Trial of Single-Vial ID93 + GLA-SE in Healthy Adults (NCT03722472), a randomized phase 1 study. The primary outcome is Local Injection Site Reactogenicity.

2. Clinical Question

3. Trial Design

This was a completed phase 1, randomized, double-blind trial with a parallel-group design. The registry record describes a quadruple masking arrangement. Enrollment was 48, and the study compared a single-vial presentation of ID93 + GLA-SE with a two-vial presentation containing lyophilized ID93 and liquid GLA-SE. The trial was designed to evaluate safety, tolerability, and immunogenicity in healthy adults.

The single-vial arm included 23 participants and the two-vial arm included 25. Both arm descriptions specify intramuscular injections on Days 0 and 56, with 2 mcg ID93 and 5 mcg GLA-SE in a 0.5 mL volume per injection. This makes presentation format the stated distinction between the two groups, while the described ingredients, amounts, route, and schedule are the same.

The registry record lists a start date of 2018-10-02 and a primary completion date of 2020-06-15; the study status is completed. The primary outcome was local injection-site reactogenicity, measured as the number of participants experiencing solicited local reactions within 7 days following each study injection. Its population was the safety population, consisting of all subjects receiving at least one study injection.

The record also lists secondary outcomes covering IgG antibody response rate and magnitude, cytokine response, and T cell response. Six secondary outcomes are posted, while the record lists 10 outcome measures overall. The registry record does not report details of the randomization procedure, allocation concealment, the trial’s original sample-size justification, or its complete statistical analysis plan. Those details should not be inferred from the randomized design or from the posted outcome summaries.

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: Safety population (n=48). All subjects receiving at least one study injection.

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: males and females, ages 18-55 inclusive

6. Primary Endpoint

The registry lists the primary outcome as Local Injection Site Reactogenicity, measured over 7 days following each injection.

The primary endpoint counts participants who experienced solicited local injection-site reactions within 7 days following each study injection. It is recorded as a number of participants, not as a measure of reaction severity, duration, or the total number of separate reactions. The endpoint’s population is the safety population: participants who received at least one study injection.

A binary participant-level endpoint is useful for summarizing whether a person experienced at least one event meeting the endpoint definition during the specified observation period. It gives a direct count for each arm and supports comparisons of event frequency between the presentations. In this trial, the posted counts are 22 participants in the single-vial arm and 21 in the two-vial arm, with arm sizes of 23 and 25, respectively.

The endpoint is limited to solicited local reactions during the stated 7-day period after each injection. It does not, on its own, describe systemic reactions, the nature or intensity of each local reaction, or events outside that observation window. The registry record names the endpoint and its time frame, but fuller operational details of how events were elicited, graded, or combined across injections are not reported in the registry record. The counts should therefore be interpreted according to the posted definition, without assuming additional details about the measurement procedure.

7. Results Posted in the Registry

• Two-vial Presentation ID93 + GLA-SE: 84.0% (21/25) versus 95.7% (22/23) on control; risk difference -11.7 percentage points (95% CI -28.3 to 5.0), risk ratio 0.88 (0.72–1.06); unadjusted two-proportion z-test p = 0.187.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either experienced a solicited local injection-site reaction within the stated time frame or did not. The posted arm counts are 22 of 23 for the single-vial presentation and 21 of 25 for the two-vial presentation. A binary outcome can be summarized as a count, as an event proportion, or through a contrast between groups. The registry record reports the counts and a risk difference for the comparison.

What does the risk difference express?

A risk difference subtracts the event proportion in one group from the event proportion in the other, following a defined group order. It is expressed on the probability scale: zero represents equal event proportions, and values on either side represent differences in opposite directions. In the posted comparison, the two-vial presentation is compared with the single-vial presentation, and the estimate is -0.117. This is the estimated contrast, not a count of participants and not a statement that every participant’s outcome differs by that amount.

The estimate is accompanied by a confidence interval from -0.283 to 0.050. A confidence interval conveys uncertainty around an estimated contrast under the method used to construct it. Values inside the interval are compatible with the observed data at the confidence level associated with that interval, under the model’s assumptions. Because the interval includes zero and extends to both sides of zero, it permits a range of possible differences in direction and magnitude. The registry record does not state the confidence level or construction method for this interval, so those details are not inferred.

What does the p-value add?

The unadjusted p-value is 0.187. A p-value describes how unusual results at least as incompatible with a specified null model would be if that model and its assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the probability that the observed result arose by chance in a general sense. It also does not measure the clinical importance of a difference. Interpretation should consider the effect estimate and its interval, not the p-value alone.

The record identifies this p-value as unadjusted. The registry record does not report a multiplicity adjustment for this endpoint, nor does it report a full statistical analysis plan. The result should not be described as adjusted for other outcomes or comparisons. The record lists 10 outcome measures and six posted secondary outcomes, but it does not report analyses for the primary endpoint in a way that permits assessment of any broader testing strategy.

Why can small group sizes limit precision?

With small groups, the observed proportions can change noticeably when a small number of participant outcomes changes. The resulting estimates may be imprecise, as reflected by uncertainty around the risk difference. This is a general statistical consideration, not a claim about unreported participant-level data. The arm sizes were 23 and 25, and the endpoint counts were 22 and 21.

For binary outcomes, the precision of an estimate depends on the number of participants and on how frequently the event occurs. When an outcome is common in both arms, the arm-level counts still do not remove uncertainty about the difference between the underlying event probabilities. The posted interval is more informative about that uncertainty than the point estimate alone. The risk ratio and odds ratio are also listed in the record, but the interpretation emphasizes the risk difference because it is the comparison metric used in the posted main estimate.

What can be said about the analysis population?

The primary endpoint population is defined as the safety population, comprising all subjects who received at least one study injection. The registry record gives this population as n=48 and reports arm sizes of 23 and 25. The record does not explain whether any endpoint observations were missing, how such observations would have been handled, or whether any alternative analysis population was used. The posted counts should therefore be read as the registry’s reported endpoint summaries, without assuming an unreported imputation or exclusion procedure.

The statistical results also need to be separated from the trial’s design objective. The trial’s phase 1 purpose included safety, tolerability, and immunogenicity; the primary endpoint concerns local reactogenicity. The endpoint comparison does not establish findings for immunogenicity, which is represented by separate secondary outcomes. Those analyses are not posted in the record. Likewise, the absence of a reported serious adverse event is a separate safety observation and does not determine the result of the local-reaction comparison.

In general, confidence intervals and p-values rely on assumptions about the data and the statistical procedure. The registry record does not report the model, variance method, or other analysis details underlying the posted comparison. Consequently, the numerical results can be described as posted, while more detailed evaluation of their derivation is not possible from the registry record alone.

10. Confidence Intervals and Precision

The posted risk-difference estimate is -0.117, with a confidence interval from -0.283 to 0.050. The interval spans zero, so the data are compatible with differences favoring either presentation as well as with no difference in the underlying event proportions. Its width signals substantial uncertainty about the magnitude of the contrast. The point estimate alone would give an incomplete account of the evidence.

A confidence interval is a range generated by a statistical procedure to represent uncertainty in an estimate. In repeated use under the procedure’s assumptions, intervals constructed at a stated confidence level have a long-run coverage interpretation. The registry record does not state the confidence level or the method used for this particular interval. It is therefore appropriate to focus on its posted endpoints and whether it includes zero, without assigning an unreported confidence level or making claims about the interval’s construction.

The group sizes were 23 in the single-vial arm and 25 in the two-vial arm. The endpoint counts were 22 and 21. These modest arm sizes mean that the estimate is based on a limited set of participant outcomes. The interval’s breadth is consistent with the need for caution: it does not tightly locate the difference, despite the point estimate favoring a lower event proportion in the two-vial arm.

The p-value of 0.187 provides another summary of compatibility with a null comparison, but it does not replace the interval or indicate the probability that either presentation is better. The registry record does not provide additional precision measures for this endpoint. Taken together, the posted estimate and interval show that the trial’s primary comparison is uncertain, and the data do not pin down a narrow range for the difference.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning values are illustrations based on the observed effect, not the trial’s original design assumptions. For this binary outcome, the listed values are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The registry record does not report the assumptions or justification used to set the original trial enrollment.

The 80% power column gives the planned number of participants per arm for a hypothetical study designed to have an 80% chance of detecting the specified effect, if that effect and the planning assumptions held. The 90% power column gives the corresponding number per arm for a higher target chance of detection under the same assumptions. These figures are not estimates of the power achieved by this completed trial.

The rows consider planning for 100%, 75%, and 50% of the observed effect. For planning for 100% of the observed effect, the illustration lists 105 participants per arm for 80% power and 140 participants per arm for 90% power. For planning for 75% of the observed effect, it lists 163 per arm for 80% power and 217 per arm for 90% power. For planning for 50% of the observed effect, it lists 311 per arm for 80% power and 415 per arm for 90% power.

Smaller effects are harder to distinguish from random variation, so planning to detect a smaller effect requires more participants. These figures are illustrative and depend on the assumptions stated above; they should not be treated as an enrollment recommendation for a future study or as evidence about the trial’s original planning. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.957; treatment proportion p₁ = 0.840; average p̄ = 0.898.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4275 = 0.8379.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4195 = 0.3531.
4. n = (0.8379 + 0.3531)² / (-0.1165)² = 104.5, rounded up to 105 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.956521739130435                          # control proportion
p1 <- 0.84                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(3722472)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 105 (80% power), 140 (90% power)
 75% of observed effect: n per arm = 163 (80% power), 217 (90% power)
 50% of observed effect: n per arm = 311 (80% power), 415 (90% power)
power.prop.test: 104.5 
Simulated power at n = 105 per arm: 0.828 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures overall and six posted secondary outcomes. The secondary outcomes include IgG antibody response rate and magnitude, cytokine response, and T cell response. The primary outcome is local injection-site reactogenicity. The record reports an unadjusted p-value of 0.187 for the posted primary comparison, but it does not report whether or how multiplicity was addressed across outcomes or analyses.

Multiplicity arises when multiple hypotheses or outcomes are assessed. When many comparisons are made, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the broader set of tests. Whether adjustment is appropriate depends on the trial’s objectives and analysis plan. Since the registry record does not report a complete statistical analysis plan or a multiplicity strategy, the p-value should be understood as the posted unadjusted result, not as an adjusted finding across all endpoints.

The registry record lists zero analyses in the analysis summary, and no analyses are posted for the secondary outcomes in the available results. That does not establish that no analyses were conducted; it means the registry record does not report them. The record does not give analysis details such as model specification, covariate adjustment, or any hierarchy among outcomes.

The primary endpoint population is the safety population: all subjects receiving at least one study injection, reported as 48 participants. The record does not report how missing endpoint observations were handled, whether any participants were excluded from an analysis, or whether a separate intention-to-treat or per-protocol population was analyzed. There is no basis in the registry record to infer a missing-data method, such as imputation or complete-case analysis.

These omissions matter because population definitions and missing-data decisions can affect how a comparison is interpreted. The posted result can still be described using its reported arm counts and estimate, but readers cannot fully reconstruct the analysis from the registry record. The original sample-size rationale and planned handling of interim analyses are also not reported in the registry record.

14. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports zero serious adverse events among 23 participants in the single-vial arm and zero among 25 in the two-vial arm. It also reports zero deaths in both groups. These are counts of participants at risk and affected for the serious-event summary, not estimates showing that serious events are impossible or that no risk exists.

For other adverse events, the record reports 23 affected participants among 23 at risk in the single-vial arm and 24 among 25 at risk in the two-vial arm. The categories should be kept distinct: the primary endpoint counts solicited local injection-site reactions within 7 days following each injection, while the adverse-event summary reports serious events and other events. The categories may describe different aspects of safety and should not be treated as interchangeable.

The registry record does not list serious adverse-event terms, and the serious-event counts are zero in both arms. Zero observed events in a small trial is a description of what was recorded during the study, not proof that an event cannot occur. These counts also do not establish comparative safety across broader populations or longer periods than those described in the record.

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

The posted primary result describes local injection-site reactogenicity among participants who received at least one study injection. The single-vial arm had 22 participants with reactions among 23, and the two-vial arm had 21 among 25. The risk-difference estimate for two-vial compared with single-vial was -0.117, with a confidence interval that includes zero. The observed point estimate therefore favors a lower event proportion in the two-vial arm, but the uncertainty interval does not establish a clear direction or precise magnitude of difference.

This result does not show that the presentations are identical. A confidence interval spanning zero can reflect uncertainty that is too broad to rule out differences in either direction. Nor does the point estimate establish that the presentations differ. The sample included 48 participants, and the primary comparison is based on relatively small arm sizes. The result is best read as an imprecise estimate from this phase 1 trial.

The endpoint is limited to solicited local reactions during the 7 days following each injection. It does not answer every safety question, describe the severity or duration of each reaction, or characterize outcomes beyond the defined period. The registry record’s separate serious adverse-event summary reports zero serious events and zero deaths in each arm, but those observations do not demonstrate absence of all possible harms.

The study also set out to evaluate immunogenicity, and the registry record lists secondary outcomes for antibody, cytokine, and T cell responses. The analyses for these secondary outcomes are not posted in the statistical results summarized in the record. The primary local-reactogenicity result cannot be used to infer immunogenicity findings.

Finally, the population consisted of healthy adults aged 18–55. The result should not be generalized beyond the studied setting without further evidence. It is a report of the trial’s posted data, not medical advice and not a conclusion about treatment or protection.

16. Why This Trial Matters Statistically

This trial is statistically informative because it compares two presentations while describing the same stated vaccine components, amounts, route, and injection schedule in each arm. A randomized parallel design provides a framework for comparing outcomes between the presentations. The primary endpoint is clearly framed as a participant count for local reactions within a specified period following each injection.

The main statistical lesson is the difference between a point estimate and the uncertainty around it. The posted risk difference is negative, but its confidence interval includes zero and extends across values on both sides. The point estimate alone might suggest a directional contrast; the interval shows why the evidence is not precise enough to settle the direction or size of the difference. The unadjusted p-value of 0.187 likewise needs to be read alongside the estimate and interval, not as a stand-alone verdict.

The trial’s limited enrollment is also relevant to interpretation. With 23 and 25 participants in the arms, the estimate reflects a small number of observed participants. The planning illustrations indicate how hypothetical sample sizes vary with the effect targeted and the desired power, but those illustrations are distinct from the trial’s original enrollment rationale, which is not reported in the registry record.

Finally, the record demonstrates why endpoint-specific interpretation matters. Local reactogenicity, serious adverse events, other adverse events, and immunogenicity outcomes are different measures. A finding about one does not substitute for results on another. The registry record’s missing analysis details and unposted secondary analyses limit how comprehensively the trial’s statistical evidence can be assessed.

17. 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 primary comparison is based on 48 participants, with 23 in the single-vial arm and 25 in the two-vial arm. These small groups limit precision, and the posted confidence interval for the risk difference includes zero. The endpoint counts are high in both arms, but the registry record does not report more detailed participant-level information that would allow evaluation of reaction severity, duration, or recurrence across injections.

The endpoint is restricted to solicited local injection-site reactions within 7 days following each study injection. The registry record does not report the detailed elicitation or grading procedures, nor does it clarify how reactions across the two injection periods were combined into the participant count. Other safety outcomes are reported separately and do not extend the endpoint definition.

The record does not report the original sample-size justification, full statistical analysis plan, randomization procedure, or allocation concealment details. It also does not report the confidence-interval construction method, missing-data handling, or any multiplicity strategy. These gaps constrain independent assessment of the posted analysis and mean that unreported procedures should not be assumed.

The record lists secondary immunogenicity outcomes, but their analyses are not posted in the statistical results. The trial population was healthy adults aged 18–55, so the primary result is specific to that study population and setting. The record’s safety summaries report no serious adverse events or deaths, but a small study cannot characterize uncommon events with precision.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Phase 1 Clinical Trial of Single-Vial ID93 + GLA-SE in Healthy Adults — NCT03722472.
• Registry record last updated 2023-06-01; status last verified 2023-05.
• Results first posted 2023-06-01.
• 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.

21. Record Summary

This completed phase 1 randomized, double-blind, parallel-group trial enrolled 48 healthy adults aged 18–55. It compared single-vial and two-vial presentations of ID93 + GLA-SE, with both arm descriptions specifying two intramuscular injections on Days 0 and 56. The primary endpoint was participants experiencing solicited local injection-site reactions within 7 days following each injection.

The registry record reports 22 participants with reactions among 23 in the single-vial arm and 21 among 25 in the two-vial arm. The posted risk-difference estimate for two-vial compared with single-vial was -0.117, with a confidence interval from -0.283 to 0.050 and an unadjusted p-value of 0.187. The interval includes zero, leaving substantial uncertainty about the direction and size of the difference.

The record reports zero serious adverse events and zero deaths in each arm. It lists secondary immunogenicity outcomes, but their analyses are not posted in the statistical results summarized in the record. Details of the original sample-size justification and several analysis procedures are not reported in the registry record.