Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients (NCT01417780), a randomized phase 2 study. The primary outcome is Number of Subjects With One or More Adverse Events (AEs) During the Treatment Period.

2. Clinical Question

The central statistical question is descriptive and comparative: what adverse-event counts were recorded in each randomized group, and how uncertain are the differences between each AB103 dose and placebo? The primary outcome counts participants with at least one event, not the total number of separate events. An individual with multiple adverse events is still counted as a participant with an event for this endpoint.

This distinction matters because the trial’s listed secondary measures address other aspects of clinical status, including C-reactive Protein (CRP), Day 14 Sequential Organ Failure Assessment (SOFA) Score, hospital length of stay, and days free of intensive care or ventilation. Those outcomes do not change the definition of the primary safety measure. The registry record lists these secondary outcomes, but results for CRP, ICU-free days and ventilator-free days are not reported in the registry record.

3. Trial Design

The registry describes a completed phase 2, randomized, triple-masked, parallel-group trial sponsored by Atox Bio Ltd. It enrolled 43 participants with necrotizing soft tissue infections. The groups received AB103 0.25 mg/kg, AB103 0.5 mg/kg, or placebo. The placebo is identified as normal saline (0.9% sodium chloride). The record states that urgent surgical intervention was scheduled as part of standard care.

The reported primary safety analysis population consisted of randomized patients who received study drug. The number analyzed for an outcome was defined as the number with non-missing data in that population. For the primary adverse-event measure, the listed group denominators are 15 for AB103 0.25 mg/kg, 17 for AB103 0.5 mg/kg, and 11 for placebo. The corresponding participant counts with one or more adverse events are 14, 16, and 9.

Triple masking indicates that the registry classifies the trial as masked, but which trial roles were masked is not reported in the registry record. The method used to generate the random allocation sequence, the allocation concealment procedure, and the planned allocation ratio are not reported in the registry record. The study’s own sample-size justification and its original statistical analysis plan are also not reported in the registry record.

The primary endpoint timeframe is 7 days. Some secondary outcomes have a 14-day timeframe, while hospital length of stay is recorded over 28 days. A treatment administration schedule and the duration of study-drug exposure are not reported in the registry record. The registry lists 25 outcome measures and 5 analyses, but the reported results available for interpretation include the primary safety outcome and a subset of secondary outcomes. The results for other listed secondary outcomes 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.

Before assignment: Of 43 randomized patients who received AB103 or placebo (intent-to-treat \[ITT\] population; safety analyses), 3 patients were excluded to form the modified intent-to-treat (mITT) population before unblinding due to protocol violations. Therefore, a total of 40 patients were included in the mITT efficacy analyses. With respect to any variable, the number of patients analyzed is the number of patients with non-missing data within the respective population.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The safety analysis population consisted of all randomized patients who received study drug (N=43). The number of patients analyzed is the number of patients with non-missing data in this population.

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: Data are from the modified intent-to-treat (mITT) population. The mITT population consisted of all randomized patients who received the proper study drug (AB103 or placebo) and dose, had a definitive surgical diagnosis of NSTI, and did not have a CD4 count \<200 cells/mm3.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With One or More Adverse Events (AEs) During the Treatment Period, measured over 7 days.

The primary endpoint is the number of participants with one or more adverse events during the treatment period, which is specified as 7 days. The registry defines an adverse event as an untoward medical occurrence in a participant who received study drug, whether or not the event is considered related to the drug. It can include an unfavorable sign, symptom, disease, or abnormal laboratory finding that occurs in temporal association with study-drug use.

This endpoint is used to describe the occurrence of any adverse event within each group. It is a participant-level count: it answers how many people experienced at least one event, rather than how many events occurred in total or how severe they were. The definition also means that the recorded event need not have been judged caused by treatment.

In the AB103 0.25 mg/kg group, 14 of 15 participants had one or more adverse events. In the AB103 0.5 mg/kg group, the corresponding count was 16 of 17; in the placebo group, it was 9 of 11. These counts describe the participants included in the safety analysis for this outcome. The endpoint alone does not describe the kinds of events, their duration, severity, or relationship to study drug; those are separate safety details. Nor does a participant count establish whether a difference between groups is due to treatment rather than chance or other factors.

7. Results Posted in the Registry

• AB103 0.25 mg/kg: 93.3% (14/15) versus 81.8% (9/11) on control; risk difference 11.5 percentage points (95% CI -14.5 to 37.6), risk ratio 1.14 (0.84–1.55); unadjusted two-proportion z-test p = 0.364.
• AB103 0.5 mg/kg: 94.1% (16/17) versus 81.8% (9/11) on control; risk difference 12.3 percentage points (95% CI -13.1 to 37.7), risk ratio 1.15 (0.85–1.56); unadjusted two-proportion z-test p = 0.304.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Day 14 Sequential Organ Failure Assessment (SOFA) Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AB103 0.25 mg/kg: mean 1.07 versus 2.70 on control; difference -1.63 (95% CI -3.44 to 0.18), standardized effect d = -0.84; z-test p = 0.077.
  • AB103 0.5 mg/kg: mean 0.71 versus 2.70 on control; difference -1.99 (95% CI -3.77 to -0.21), standardized effect d = -1.05; z-test p = 0.029.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AB103 0.25 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for AB103 0.5 mg/kg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Day 14 Sequential Organ Failure Assessment (SOFA) Score Less Than or Equal to 1

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • AB103 0.25 mg/kg: 71.4% (10/14) versus 40.0% (4/10) on control; risk difference 31.4 percentage points (95% CI -7.1 to 69.9), risk ratio 1.79 (0.78–4.09); unadjusted two-proportion z-test p = 0.124.
  • AB103 0.5 mg/kg: 92.9% (13/14) versus 40.0% (4/10) on control; risk difference 52.9 percentage points (95% CI 19.6 to 86.1), risk ratio 2.32 (1.07–5.03); unadjusted two-proportion z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AB103 0.25 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for AB103 0.5 mg/kg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Hospital Length of Stay (LOS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AB103 0.25 mg/kg: mean 17.10 versus 20.00 on control; difference -2.90 (95% CI -8.79 to 2.99), standardized effect d = -0.38; z-test p = 0.334.
  • AB103 0.5 mg/kg: mean 17.40 versus 20.00 on control; difference -2.60 (95% CI -8.89 to 3.69), standardized effect d = -0.31; z-test p = 0.418.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AB103 0.25 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AB103 0.5 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary findings do not form a single consistent pattern across outcome types. The SOFA measures show lower posted group means or more participants meeting the specified threshold in the AB103 groups than in placebo, while the hospital length-of-stay estimates are less clearly separated. The secondary comparisons also differ in their overall and pairwise analyses. This range of results is a reason to interpret each measure according to its definition, method, and uncertainty rather than treating all outcomes as interchangeable evidence.

These outcomes complement the primary safety endpoint but answer different questions. SOFA score describes organ dysfunction, the threshold version classifies participants according to a specified score, and hospital length of stay measures time in hospital. CRP, ICU-free days and ventilator-free days are also listed as secondary outcomes, but their results are not reported in the registry record. Differences across these measures do not directly establish a difference in adverse-event risk, which is what the primary endpoint measures.

Unadjusted secondary results carry less weight because multiple outcomes and comparisons create more opportunities for chance findings. The registry record does not report a multiplicity-adjustment plan or an adjusted set of secondary p-values. General explanation: when many hypotheses are tested, the chance of obtaining at least one apparently noteworthy result by chance can increase. Without a stated testing hierarchy or adjustment, isolated secondary p-values should be treated as exploratory rather than as confirmatory evidence.

The overall secondary pattern can help identify questions for future study, but it does not resolve the primary safety comparison or replace its uncertainty. Nor does a nominally small secondary p-value by itself show that a result is robust to different analysis choices, missing data, or multiplicity. The registry record does not report enough detail to assess all those issues.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• C-reactive Protein (CRP)
• Day 14 Sequential Organ Failure Assessment (SOFA) Score
• Day 14 Sequential Organ Failure Assessment (SOFA) Score Less Than or Equal to 1
• Hospital Length of Stay (LOS)
• Intensive Care Unit-free Days (ICU-free Days)
• Ventilator-free Days

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

The primary comparisons use risk differences, contrasting the proportion of participants with an adverse event in each AB103 group with the proportion in placebo. A risk difference is expressed on the probability scale: zero represents no difference, a positive estimate means a higher observed event risk in the AB103 group, and a negative estimate means a lower observed event risk. For the 0.25 mg/kg comparison, the estimate is 0.115; for the 0.5 mg/kg comparison, it is 0.123. These are unadjusted comparisons based on the posted group counts.

General explanation: a risk difference is an absolute contrast, not a relative measure. Relative risks and odds ratios answer different questions and can give a different numerical impression, especially when an outcome is common. The registry record also includes relative-risk and odds-ratio estimates, but those measures do not replace the risk-difference scale used for the main comparisons.

How should confidence intervals and p-values be read?

General explanation: a confidence interval describes a range of effect values compatible with the observed data under the method’s assumptions. A wider interval indicates less precision. When an interval for a difference includes zero, it does not rule out no difference at the confidence level used for that interval. It may also include potentially important differences in either direction, so the estimate should not be reduced to a yes-or-no conclusion.

A p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary comparison p-values are unadjusted. The primary outcome’s sponsor-reported inferential method and p-value are not reported in the registry record; the displayed primary contrasts are unadjusted re-calculations from posted summary counts.

The registry reports overall analyses for several secondary outcomes. Day 14 SOFA score was analyzed with ANOVA, with p=0.016 for the three groups. The binary Day 14 SOFA outcome was analyzed with a Chi-squared test, with p=0.019. Hospital length of stay was analyzed with a Wilcoxon (Mann-Whitney) method, with p=0.11. These are overall group tests, not the same as the pairwise AB103-versus-placebo contrasts. The registry record does not report the full specifications for these tests, including any adjustments or assumptions beyond the named method.

Why are continuous and binary outcomes handled differently?

The primary adverse-event endpoint and the SOFA threshold outcome are binary at the participant level: each participant either meets the specified event definition or does not. SOFA score and hospital length of stay are continuous measures summarized by means and standard deviations in the posted results. A mean describes the group average; a standard deviation describes how spread out individual observations are around that average.

General explanation: continuous outcomes can be analyzed by comparing means when the analysis assumptions are appropriate. Rank-based methods such as Wilcoxon compare the ordering of observations and do not require the same interpretation as a difference in means. For outcomes with skewed distributions or outliers, a mean and standard deviation may not fully convey the distribution. The registry record does not provide participant-level observations or enough distributional information to assess those features.

What can the small groups tell us?

The group sizes are small, and the posted confidence intervals are correspondingly important for judging uncertainty. General explanation: sparse data can make estimates sensitive to a small number of observations, particularly for binary outcomes. A result that appears numerically different between groups may still be estimated imprecisely. Conversely, a non-small p-value does not demonstrate that groups are equivalent. The primary comparisons therefore need to be read through their effect estimates and intervals, not p-values alone.

The registry’s stated planning illustration uses the observed effect as a starting point and varies the effect to detect. It assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For these non-time-to-event outcomes, the listed planning values are participants per arm. The illustration is not the trial’s original design calculation; the original sample-size assumptions are not reported in the registry record. These projected sample sizes are planning illustrations, not observed power.

11. Confidence Intervals and Precision

The primary risk-difference estimates are imprecise. For AB103 0.25 mg/kg versus placebo, the confidence interval runs from -0.145 to 0.376. For AB103 0.5 mg/kg versus placebo, it runs from -0.131 to 0.377. Both intervals cross zero, leaving no clear separation between a no-difference value and a range of effects in either direction. This uncertainty is consistent with the modest group sizes and the high event counts in all groups.

General explanation: an interval is more informative than a point estimate alone because it conveys how much uncertainty remains around the estimated contrast. A confidence interval that includes zero should not be read as proof of no effect. Nor should its point estimate be treated as a precise forecast of what would occur in a larger population. The interval’s span captures uncertainty under the calculation’s assumptions, not every possible source of bias or variability.

The secondary results also vary in precision. For the 0.25 mg/kg SOFA mean contrast, the confidence interval includes zero; for the 0.5 mg/kg contrast, the interval runs from -3.773 to -0.207. The two binary SOFA comparisons have confidence intervals of different widths, and the interval for the 0.25 mg/kg contrast includes zero. Both hospital-length-of-stay pairwise confidence intervals include zero. These intervals caution against treating point estimates as definitive, even where a reported p-value is small.

Precision is distinct from clinical importance. The registry record does not specify a threshold for a clinically important difference, and such a threshold is not reported in the registry record. The estimates and intervals therefore describe statistical uncertainty, but cannot by themselves determine whether an observed difference would matter clinically.

12. 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 display is a planning illustration for two-group comparisons, rather than a description of the trial’s enrollment target. For these outcomes, its figures are participants per arm, not totals across groups. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for planning is a stated fraction of the observed effect. The original design assumptions and the trial’s own sample-size justification are not reported in the registry record.

Each planning row asks what group size would be needed if the effect to detect were 100%, 75%, or 50% of the observed effect. The 80% power column describes the participant count per arm calculated to give an 80% chance of detecting the specified effect under the stated assumptions, if that effect is real. The 90% power column uses a higher target chance of detection, so it generally requires more participants per arm. Smaller effects are harder to distinguish from chance variation and therefore require more participants. For example, the planning illustration for the primary AB103 0.25 mg/kg comparison lists 128 participants per arm for 80% power at 100% of the observed effect, and 613 participants per arm at 50% of the observed effect.

These projections are not observed power. Observed power is not a measure of how likely the trial’s conclusion is to be correct; the planning values instead show how sample size changes under specified assumptions and effect sizes. The registry record does not report whether the original trial design used these assumptions or planning targets. The display should therefore be read as an illustration based on the observed estimates, not as a reconstruction of the study’s original design process.

13. 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 = 0.818; treatment proportion p₁ = 0.933; average p̄ = 0.876.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4665 = 0.9143.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4593 = 0.3866.
4. n = (0.9143 + 0.3866)² / (0.1152)² = 127.6, rounded up to 128 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 <- 0.818181818181818                          # control proportion
p1 <- 0.933333333333333                          # 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(1417780)
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 = 128 (80% power), 171 (90% power)
 75% of observed effect: n per arm = 251 (80% power), 335 (90% power)
 50% of observed effect: n per arm = 613 (80% power), 820 (90% power)
power.prop.test: 127.6 
Simulated power at n = 128 per arm: 0.810 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures and reports several secondary analyses, but a plan for controlling multiplicity is not reported in the registry record. In particular, it is not reported whether the study designated a hierarchy among secondary endpoints, adjusted p-values for multiple comparisons, or treated the reported tests as exploratory. The primary endpoint includes two dose-versus-placebo comparisons, and the secondary results include both overall group tests and pairwise contrasts. Without a prespecified multiplicity strategy, nominal p-values should not be interpreted as if they were the only hypothesis tests performed.

The primary safety population is described as all randomized patients who received study drug, with the number analyzed determined by non-missing outcome data. The primary denominators are 15, 17, and 11 across the three groups. The record does not provide details about missing primary outcome observations beyond the rule that non-missing data were analyzed. For secondary outcomes, the analyzed group counts vary by outcome. The reasons for those differences, the handling of missing values, and any imputation method are not reported in the registry record.

The registry record does not report the full statistical analysis plan, including whether analyses were adjusted for baseline characteristics, how protocol deviations were handled, or whether any interim analyses were performed. It also does not report details that would establish whether the analyzed population for each secondary endpoint followed an intention-to-treat approach. These omissions limit the ability to assess the prespecification and robustness of the reported tests.

General explanation: multiplicity and missing data are separate concerns. Multiplicity affects how confidently a collection of p-values can be interpreted; missingness can affect the comparability and representativeness of the analyzed groups. Neither issue can be resolved simply by looking at a small p-value. The available estimates remain useful descriptions of the posted results, but the unreported analysis details limit stronger inferential claims.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (20.0%), respiratory failure (17.6%), septic shock (9.1%), renal failure acute (9.1%), bradycardia (9.1%).

The serious adverse event counts are 8 of 15 participants in the AB103 0.25 mg/kg group, 5 of 17 in the AB103 0.5 mg/kg group, and 4 of 11 in the placebo group. Deaths are listed for 1, 1, and 2 participants, respectively. These are group-level counts; they do not establish the cause of an event or whether an event was considered related to study drug. The registry record does not report further details about event timing, severity grading, or individual-level overlap between serious events and deaths.

The record lists hypotension (20.0%), respiratory failure (17.6%), septic shock (9.1%), renal failure acute (9.1%), bradycardia (9.1%), and cardiac arrest (9.1%) among the top serious-event terms. Those percentages should be read as reported event summaries, not as evidence that the events were caused by treatment. In a small trial, serious safety counts can be unstable and descriptive comparisons should be interpreted cautiously. The counts alone cannot determine comparative safety, especially without fuller information on event definitions, clinical context, and attribution.

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

The registry results describe a small randomized comparison of two AB103 dose groups with placebo in patients with necrotizing soft tissue infections. For the primary endpoint, adverse events were frequent in all three groups. The unadjusted risk-difference estimates favor neither a definitive conclusion of greater risk nor a conclusion of no difference: their confidence intervals include zero and extend across a broad range. The results therefore leave substantial uncertainty about the size and direction of the between-group differences.

The secondary outcomes provide additional descriptions of organ-function scores and hospital stay, but they do not remove the uncertainty in the primary safety comparison. Several secondary contrasts have nominally small p-values, while others do not; a multiplicity plan is not reported in the registry record. Results for some listed secondary outcomes are also not reported in the registry record. The pattern should be read as a set of limited, outcome-specific findings rather than as a single definitive overall result.

General explanation: a randomized design can help make group comparisons meaningful, but randomization does not guarantee that small groups will be balanced on every characteristic. The registry record does not report baseline characteristics or enough details about allocation procedures to evaluate balance and implementation. Likewise, statistical significance is not the same as clinical importance, and a non-significant result is not proof of equivalence.

These data do not establish that AB103 causes or prevents adverse events, and they do not establish that the groups have the same safety profile. They are not a basis for medical advice. The results are best understood as estimates from this completed phase 2 trial, with substantial uncertainty and limited detail on analysis choices. Any broader claim would require evidence beyond the posted results, including a fuller assessment of the design, analysis, and complete outcome reporting.

17. Why This Trial Matters Statistically

This trial illustrates a central challenge in clinical biostatistics: an observed difference is not the same as a precise or conclusive difference. The primary outcome counts participants with at least one adverse event, and the event counts are high across all groups. Although the point estimates distinguish the AB103 groups from placebo, their confidence intervals are wide and include no difference. Reporting the counts, estimates, intervals, and p-values together makes the uncertainty visible rather than allowing a single statistic to dominate interpretation.

It also demonstrates why endpoint definitions matter. The primary safety outcome counts people with an event, not total events, and the definition includes events regardless of whether investigators considered them related to study drug. Serious adverse event counts and deaths provide other safety descriptions, but they are not interchangeable with the primary endpoint. A reader needs to distinguish the question each measure answers before comparing the results.

The secondary results show how a study can report different patterns across outcomes, analysis methods, and timeframes. Overall tests and pairwise contrasts address different hypotheses, while unadjusted testing across numerous outcomes increases the need for caution. The registry does not report a multiplicity plan or the full statistical analysis plan, so the status of secondary findings as confirmatory or exploratory cannot be established from the record.

Finally, the planning illustrations connect uncertainty in an observed estimate with future study design. They show that planning for smaller effects calls for larger participant counts under the stated assumptions. They do not describe the original trial’s design calculation or substitute for a prespecified justification. Together, these features make the record useful for understanding how endpoint choice, precision, and analysis transparency shape interpretation of a clinical trial.

18. 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 group sizes are small, and the primary confidence intervals are broad. As a result, the estimates allow a wide range of possible differences in adverse-event risk. The registry record gives limited information about participant characteristics, so the comparability of the groups at baseline cannot be assessed from the posted details. Randomization is reported, but the sequence-generation and allocation-concealment methods are not reported in the registry record.

The record identifies triple masking but does not state which roles were masked or how masking was maintained. The primary endpoint is defined as any adverse event during 7 days; additional detail about event ascertainment and adjudication is not reported in the registry record. The listed serious adverse event terms and deaths provide descriptive safety information, but event-level timing, relatedness, and participant overlap are not specified.

For several outcomes, the registry reports group summaries and selected analyses without a complete statistical analysis plan. The primary sponsor-reported inferential method is not reported in the registry record, and multiplicity handling is not reported. Missing-data reasons and methods are also not reported, while the number analyzed varies across secondary outcomes. These gaps make it difficult to evaluate sensitivity to analysis choices or missing observations.

Not all listed secondary outcomes have results in the registry record. In particular, results for CRP, ICU-free days, and ventilator-free days are not reported in the registry record. The trial’s original sample-size justification, interim-analysis plan, and stopping rules are not reported in the registry record. The sample-size illustrations based on observed effects cannot address those design limitations or establish how the trial was originally planned.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients — NCT01417780.
• Registry record last updated 2021-08-18; status last verified 2021-07.
• Results first posted 2021-08-18.
• 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.

22. Record Summary

This completed phase 2 randomized, triple-masked, parallel-group trial evaluated AB103 at 0.25 mg/kg and 0.5 mg/kg against placebo in patients with necrotizing soft tissue infections. The primary endpoint was the number of participants with one or more adverse events during the 7-day treatment period. The primary event counts were 14 of 15, 16 of 17, and 9 of 11, respectively.

The unadjusted risk-difference confidence intervals include zero for both comparisons with placebo, and the estimates are imprecise. Secondary results vary across SOFA measures and hospital length of stay; multiplicity handling is not reported in the registry record. Several listed secondary outcomes and important design and analysis details are also not reported in the registry record. The posted results are descriptive and do not establish a definitive comparative safety conclusion.