Anti-LPS Antibody Treatment for Pediatric NAFLD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anti-LPS Antibody Treatment for Pediatric NAFLD (NCT03042767), a randomized phase 2 study. The primary outcome is Percent Change in Alanine Aminotransferase (ALT) Level.

2. Clinical Question

The contrast is between two randomized groups over the same treatment period. The main outcome is a change from baseline, expressed as a percentage, rather than the absolute ALT value at the end of treatment. The registry record does not report a target difference that investigators considered clinically important, or additional details about how standard of care was delivered.

3. Trial Design

This was a phase 2, randomized, double-masked, parallel-group trial of IMM-124E and placebo in children with NAFLD. The registry record lists enrollment of 40 and a completed study. The recorded start date is 2017-02-01, and primary completion is listed as 2019-10-23. These are registry dates, not a description of how long each participant was followed.

Participants assigned to IMM-124E were to receive 600mg of powder three times daily for twelve weeks. Participants assigned to placebo were to receive placebo powder on the same schedule. The study summary describes both treatments as being used with standard of care. Details of that care are not reported in the registry record.

The randomized, parallel design compares separate groups assigned to different treatments. Double masking indicates that the registry identifies the study as masked, but it does not report who specifically was masked or how masking was maintained. Details of sequence generation, allocation concealment, stratification, and site procedures are not reported in the registry record.

Although enrollment was 40, the posted primary outcome reports 11 participants per group. The registry record does not explain the difference between the enrollment figure and the outcome counts. It also does not describe the original sample-size justification or say whether the study was designed to provide a definitive test. The study is described as a pilot, which is relevant when interpreting the size and precision of its estimates.

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: 40 participants were enrolled, 15 of them screenfailed. 25 participants were randomized.

Overall Study

Reasons for not completing this period:

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 Percent Change in Alanine Aminotransferase (ALT) Level, measured over Baseline (Week 0), End of Treatment (Week 12).

The primary endpoint is percent change in alanine aminotransferase (ALT) from baseline, identified as Week 0, to the end of treatment, identified as Week 12. The registry describes ALT as the measure used to assess liver inflammation for the study’s main objective. ALT is a continuous laboratory measure, so the reported group results are means with standard deviations.

Expressing change as a percentage focuses the comparison on relative change from each participant’s baseline rather than on the group’s end-of-treatment level alone. The primary comparison is the difference between the mean percentage changes in the IMM-124E and placebo groups. A positive difference means the IMM-124E group’s reported mean change was higher than the placebo group’s, using the comparison direction in the registry results. The clinical interpretation of that direction depends on the endpoint and should not be confused with a treatment conclusion.

The registry record does not report a threshold for a clinically important ALT change, or further details about the laboratory measurement and analysis procedures. The endpoint therefore describes a measured change over the treatment period; by itself, it does not establish how meaningful that change is for participants or how it relates to other aspects of liver health.

7. Results Posted in the Registry

• IMM-124E Group: mean 11.99 versus -7.99 on control; difference 19.98 (95% CI 1.83 to 38.13), standardized effect d = 0.92; z-test p = 0.031.

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.

Percent Change in Visceral Adiposity

• 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:
  • IMM-124E Group: mean 1.23 versus 1.77 on control; difference -0.54 (95% CI -7.94 to 6.86), standardized effect d = -0.06; z-test p = 0.886.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IMM-124E Group and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change in Hepatic Fat Percent

• 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:
  • IMM-124E Group: mean -5.70 versus -6.61 on control; difference 0.91 (95% CI -13.28 to 15.10), standardized effect d = 0.05; z-test p = 0.900.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IMM-124E Group and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change in PROMIS Fatigue Questionnaire 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:
  • IMM-124E Group: mean -10.17 versus -4.67 on control; difference -5.50 (95% CI -18.94 to 7.94), standardized effect d = -0.34; z-test p = 0.422.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IMM-124E Group and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary comparisons do not present the same pattern as a clear, consistent separation between treatment groups. Their estimates are close to zero for some measures, while the fatigue measure has a wider difference estimate; the intervals for all three posted secondary comparisons include zero. In general, this means the observed results do not clearly distinguish the groups on those measures, but it does not establish that the groups are equivalent.

These outcomes add context to the primary ALT result because they concern other metabolic, liver-related, or participant-reported measures over the same baseline-to-end-of-treatment period. They are not substitutes for the primary endpoint, and their results do not confirm or negate the primary comparison. The registry lists 15 secondary outcomes, while the posted outcome information includes results for selected secondary measures. The record does not report a prespecified hierarchy for interpreting them.

Each unadjusted secondary p-value is considered without accounting for the number of outcomes tested. In general, testing many outcomes increases the chance that at least one result will appear notable by chance, even when there is no corresponding underlying difference. Without a reported multiplicity plan, individual secondary results should therefore carry less weight than a prespecified primary comparison. Their estimates and intervals are more useful as descriptions of uncertainty and as context for future research than as independent confirmation of a treatment effect.

The secondary results are also based on 11 participants per group, and the record does not explain missingness or analysis-population choices. This limits how much can be inferred from apparent patterns across endpoints. No adjustment for baseline values or other covariates is reported, and it is not reported whether the secondary analyses were specified before results were examined. These uncertainties favor a cautious, descriptive reading rather than a definitive conclusion across outcomes.

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

• Percent Change in Fasting Glucose Level
• Change in Fasting Insulin Level
• Change in Hemoglobin A1C Level
• Change in Adipose Tissue Insulin Resistance (Adipo-IR)
• Change in Triglyceride/HDL (TG/HDL) Ratio
• Percent Change in Blood Glucose Level
• Change in Insulin Levels
• Percent Change in Body Mass Index (BMI) Z-Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s result is expressed as a percent change in ALT, and the registry reports the mean and standard deviation for each group. The main comparison is the difference between those two group means. This is a straightforward way to describe the average separation between randomized groups on the endpoint’s stated scale.

What does the mean difference describe?

The IMM-124E group mean was 11.99 and the placebo group mean was -7.99. The reported mean difference was 19.98, with the comparison oriented as IMM-124E minus placebo. This means that the average percentage change was higher in the IMM-124E group by the reported amount. It does not describe each participant’s response, and it does not show how many participants improved or worsened.

The standard deviation describes the spread of participant results around a group mean. The reported standard deviations were 25.87 for IMM-124E and 16.54 for placebo. In general, a larger standard deviation means the individual observations are more dispersed around their group average. It is not the same as the uncertainty in the estimated group mean or the uncertainty in the difference between groups.

How should the confidence interval be read?

The registry reports a confidence interval from 1.835 to 38.13 for the mean difference. A confidence interval gives a range of values compatible with the observed data and the method’s assumptions; it communicates uncertainty about the estimated difference. It is not a range containing a fixed proportion of individual participant outcomes, and it does not assign a probability to the true effect being within this particular interval. The confidence level and the specific procedure used to construct the interval are not reported in the registry record.

What does the p-value add?

The unadjusted p-value for the primary comparison is 0.031. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of the difference. Because the registry labels this result unadjusted, it should not be read as accounting for the testing of other outcomes.

The registry record does not describe the exact test used, the model specification, or any covariate adjustment. It reports 11 participants in each group for this outcome, but it does not say which analysis population was used or how missing outcome data were handled. Those details matter because statistical estimates and their uncertainty can depend on the analysis method and the observations included.

Why does variation matter?

When participant results vary considerably, an estimated group difference is less precise unless the study has enough observations to distinguish the group averages from that variation. In general, the standard error reflects uncertainty in an estimate, while the standard deviation describes variation among observations. The registry reports standard errors for the two group means as 4.987 and 7.8; the precise procedure used to calculate them is not described. The confidence interval for the difference is the most direct posted summary of uncertainty about the primary contrast.

In general, over-dispersion means that observed variability is greater than a statistical model expects. A model that fails to allow for extra variability can underestimate uncertainty and make evidence appear stronger than it is. The registry record does not say that over-dispersion was assessed or that a model requiring such an assessment was used; this concept is relevant as general statistical context, not as a claim about this trial’s analysis.

What can be inferred about the analysis plan?

The record identifies the primary outcome and posts group summaries and a comparison, but does not report a detailed statistical analysis plan. The model, assumptions, missing-data approach, analysis population, and handling of repeated measures are not reported in the registry record. No interim analyses or original sample-size justification are reported there either. The posted statistics can be described, but these omissions prevent a full audit of how the analysis was planned and carried out.

The trial’s sample-size planning illustrations are separate from the primary outcome analysis. They use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set to a stated fraction of the observed effect. They are prospective planning examples based on the observed estimate, not evidence that the trial had a particular probability of detecting its result. The original design assumptions for this trial are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is 19.98, and its reported confidence interval extends from 1.835 to 38.13. The interval excludes zero, but it also spans a substantial range of possible differences. The estimate therefore has uncertainty about its magnitude even though the posted interval is on one side of zero. The confidence level and construction method are not reported in the registry record, so the interval should be interpreted using only the information the record provides.

Only 11 participants per group contribute to the posted primary outcome. A small outcome count can limit precision, particularly when the observed results vary across participants. The standard deviations of 25.87 and 16.54 indicate spread within both groups. The confidence interval expresses uncertainty about the difference between group means; it does not show the range of individual ALT changes.

Precision and clinical importance are separate questions. The interval addresses uncertainty about the statistical contrast, while the registry record does not provide a threshold for deciding what size of ALT difference would be clinically important. Nor does the interval establish whether the result would be similar in another study or population. The trial is identified as a pilot, and the posted counts and interval support cautious interpretation rather than a claim of a precisely determined effect.

For the posted secondary comparisons, the intervals include zero. That pattern indicates considerable uncertainty about the direction and size of those group differences. It does not demonstrate equivalence between groups: showing that differences are small enough to be unimportant would require a prespecified equivalence margin and an appropriate analysis, neither of which is reported in the registry record.

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 planning figures are participants per arm, not total participants and not total events. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a target effect equal to a stated fraction of the observed effect. These assumptions describe the illustrations; the trial’s original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one and the model assumptions hold. The 90% power column gives the corresponding per-arm planning number for a design with a 90% chance under the same conditional interpretation. These are planning quantities, not guarantees about a future study’s result.

As the assumed effect gets smaller, more participants are needed to distinguish it from random variation under the same planning approach. The illustrations use fractions of the observed effect rather than an independently established clinically important effect. Consequently, they show how sample size changes with the selected target effect; they do not establish what sample size is appropriate for a definitive study.

These figures are not observed power. Observed power is not an informative substitute for examining the estimated effect and its uncertainty after a study. The trial enrolled 40, while the posted primary outcome reports 11 participants in each group; the record does not explain this difference. The planning illustrations should not be used to infer why the observed outcome counts were what they were.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 19.980; pooled standard deviation σ = 21.712.
2. n = 2 × (1.96 + 0.842)² × 21.712² / 19.980² = 18.5, rounded up to 19 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
delta <- 19.98                      # observed difference in means
sigma <- 21.7120761328805                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3042767)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 19 (80% power), 25 (90% power)
 75% of observed effect: n per arm = 33 (80% power), 45 (90% power)
 50% of observed effect: n per arm = 75 (80% power), 100 (90% power)
power.t.test: 19.5 
Simulated power at n = 19 per arm: 0.789 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 identifies one primary outcome and lists 15 secondary outcomes. The primary comparison has an unadjusted p-value, and the posted secondary comparisons also have unadjusted p-values. The registry record does not report a strategy for controlling the chance of false-positive findings across these outcomes, such as a testing hierarchy or a multiplicity adjustment. As a result, the primary result can be described as posted, but the strength of evidence should be considered in the context of the several outcomes being evaluated.

Multiplicity matters because repeated statistical tests create more opportunities for a result to appear unusual by chance. In general, an adjustment or prespecified ordering can help distinguish the main confirmatory question from exploratory comparisons. No such approach is reported in the registry record. This absence does not show that no approach was used; it means the record does not document one.

The posted primary endpoint count is 11 in each group, compared with registry enrollment of 40. The record does not explain this difference or identify whether participants were excluded, lacked a measurement, or were handled in another way. The reason should not be inferred from the counts alone. Missing-data handling, imputation, and sensitivity analyses are not reported in the registry record.

The analysis population is also not reported. It is therefore unclear from the registry record whether the posted results are based on all randomized participants, participants who completed treatment, or another defined group. Details of adherence and withdrawals are not reported. The record also does not describe interim analyses, the original sample-size justification, or a detailed statistical analysis plan. These omissions limit assessment of how the analysis choices may affect the posted estimates and their interpretation.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 12 participants at risk in the IMM-124E group and zero among 13 at risk in the placebo group. It also reports zero deaths in both groups. No serious adverse event terms are listed in the record.

These figures describe the recorded counts and denominators; they do not establish that serious events could not occur. The safety denominators differ from the 11 participants per group reported for the primary outcome, and the registry record does not explain the difference. The counts at risk should therefore be read as the denominators reported for these safety entries, not assumed to represent the endpoint analysis population.

The record also reports other adverse events affecting 8 of 12 participants in the IMM-124E group and 10 of 13 in the placebo group. These are listed separately from serious adverse events. The posted safety information does not provide further detail on event types, severity, timing, or attribution. The counts alone do not support conclusions about comparative safety.

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

The central posted result is a mean difference of 19.98 percentage points in percent change in ALT, with the IMM-124E group having the higher mean change. The confidence interval ranges from 1.835 to 38.13, and the unadjusted p-value is 0.031. These statistics describe the observed comparison and its uncertainty; they do not by themselves determine whether the difference is clinically important.

The study summary frames ALT as a measure of liver inflammation and identifies reduction in ALT as the study objective. The posted direction is therefore important to describe accurately: the mean percentage change was higher in the IMM-124E group than in the placebo group. This statistical finding should not be translated into advice or a general claim about what treatment does. The registry record does not report a clinically meaningful threshold for the endpoint, and the trial is described as a pilot.

The result does not show that every participant had a higher ALT change, or that the groups differed on all relevant outcomes. Group means conceal individual variation. The secondary comparisons are uncertain and do not supply clear corroboration across the posted measures. The record does not report multiplicity handling, missing-data procedures, or the analysis population, which are important for judging the robustness of the findings.

Nor does the result establish what would happen with a different treatment duration, population, or care context. The trial concerns children with NAFLD and a twelve-week treatment period. Further details about participant characteristics and standard of care are not reported in the registry record. The appropriate conclusion is limited to describing the posted data and their precision, without extending them beyond the study’s recorded comparison.

17. Why This Trial Matters Statistically

This trial illustrates why a reported mean difference should be read together with its direction, interval, and study context. The primary point estimate is separated from zero according to the posted interval, but the interval still covers a wide range of possible magnitudes. The group means and standard deviations also show why the estimate should not be treated as a description of every participant’s experience.

It also highlights the distinction between a pilot study’s observed effect and a design target for later research. The sample-size illustrations are based on fractions of the observed effect, under stated planning assumptions. Because estimates from small studies can be imprecise, planning directly from an observed effect can be sensitive to that uncertainty. The illustrations are not the trial’s original justification and do not establish a definitive target sample size.

Multiplicity and reporting completeness matter as well. The registry lists numerous secondary outcomes, but does not report a multiplicity strategy, missing-data approach, or analysis population. Those details are necessary for a fuller appraisal of how much confidence to place in individual findings. The primary result can be described faithfully while still recognizing these limits.

For biostatisticians and clinical researchers, the record is a useful example of separating a statistical signal from clinical interpretation, and a planning illustration from observed trial evidence. Transparent reporting of analysis decisions, participant flow, and prespecified outcome priorities would make the results easier to evaluate and reproduce.

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 primary outcome is reported for 11 participants per group, although enrollment is listed as 40. The registry record does not explain this difference. Without participant flow, reasons for missing measurements, or an analysis population definition, it is not possible to determine from the record how representative the posted outcome counts are of the randomized groups.

The study is described as a pilot and reports a twelve-week treatment period. This is a limited setting for interpreting the size and precision of an endpoint change, and the result should not be generalized to longer treatment or other populations. The record does not provide further participant characteristics, so the extent to which the study population represents children with NAFLD more broadly cannot be assessed.

ALT is used as a measure of liver inflammation in the study summary, but the record does not report a clinically important change threshold or additional outcomes that would establish the broader significance of an ALT difference. The primary result’s direction is higher mean percent change in the IMM-124E group. Statistical interpretation should retain that direction and avoid treating the point estimate as evidence of benefit.

Several analysis details are absent: the exact statistical test, covariate adjustment, handling of missing data, analysis population, and multiplicity strategy are not reported in the registry record. The standard of care described in the summary is not further specified. Safety information is also limited to counts and denominators, without event descriptions. These trial-specific reporting gaps constrain interpretation of both efficacy-related outcomes and safety counts.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Anti-LPS Antibody Treatment for Pediatric NAFLD — NCT03042767.
• Registry record last updated 2021-05-24; status last verified 2021-04.
• Results first posted 2021-01-05.
• 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

The registry record describes a completed phase 2, randomized, double-masked, parallel-group pilot trial of IMM-124E versus placebo in children with NAFLD. The study summary identifies a twelve-week treatment period alongside standard of care. Enrollment is listed as 40.

The primary outcome is percent change in ALT from Week 0 to Week 12. Its posted mean difference was 19.98 percentage points, with a confidence interval from 1.835 to 38.13 and an unadjusted p-value of 0.031. The outcome count was 11 participants per group. The direction of the estimate was a higher mean percentage change in the IMM-124E group.

The record also posts selected secondary outcomes and safety counts. It does not report a detailed analysis plan, multiplicity handling, missing-data methods, or reasons for the difference between enrollment and outcome counts. These limitations should accompany interpretation of the results.