Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH) (NCT03883607), a randomized phase 2 study. The primary outcome is Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007).

2. Clinical Question

The study is listed as phase 2 and terminated, with enrollment of 10. Its stated focus was pharmacokinetic profile and safety and tolerability in a pediatric population. The registry also lists pharmacodynamic assessments involving liver markers and glucose homeostasis. Those additional outcomes could describe changes in measured biological markers, but the registry record does not report their results.

3. Trial Design

This was a randomized, multicenter, open-label, parallel-group phase 2 study sponsored by Genfit. Participants were assigned to elafibranor 80 mg or 120 mg, taken orally once daily for 12 weeks. There was no masking, and the record does not describe a placebo or usual-care comparator. Enrollment was 10. The registry lists the study as terminated; it does not report a reason for termination.

The brief description characterizes the treatment period as 3 months. The registered arm descriptions specify 12 weeks. The primary outcome concerned pharmacokinetics: maximum observed plasma concentration of elafibranor and GFT1007. Sampling was scheduled at pre-dose on Day 1; at pre-dose and multiple post-dose times on Day 29; and at 24 hours after the previous day's dose on Day 30 and Day 85. The record defines Cmax as the maximum observed plasma concentration.

Secondary outcomes covered changes from baseline in liver enzymes and other liver markers, as well as fasting plasma glucose. Assessments were scheduled across Days 15, 29, 57, 85, and 113, with the precise schedule varying by marker. These outcomes indicate that the protocol included a broad set of pharmacodynamic measurements, but their results are not reported in the registry record.

The registry record does not report a sample-size justification, detailed allocation procedure, or complete statistical analysis plan. It also does not state why the trial was terminated or whether all planned assessments were completed. These gaps limit assessment of how closely the posted record reflects the study as conducted.

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: Screening was performed up to 4 weeks before study drug administered. Randomization was stratified by age (Cohort 1: greater than or equal to \[\>=\] 12 to less than or equal to \[\<=\] 17 years of age and Cohort 2: \>=8 to \<=11 years of age) and participant's historical fibrosis severity stage (stratum 1: fibrosis stage 0 to 1 and stratum 2: fibrosis stage 2 to 3). Due to lack of efficacy study was prematurely terminated, only Cohort 1 participants were involved in this study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on PK population that included all participants who had received at least 1 dose of the study drug, did not had protocol deviations or adverse events (AEs) that significantly affected the PK, and had at least 1 post-dose PK sample.

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: Analysis was performed on intent-to-treat (ITT) population that had included participants who were randomized and had received at least 1 dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007), measured over Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration.

The primary endpoint was maximum observed plasma concentration, or Cmax, for elafibranor and its active metabolite GFT1007. It is expressed in nanograms per milliliter (ng/mL). Cmax describes the highest measured concentration in the sampled blood-plasma profile. Pharmacokinetic measurements help characterize drug exposure and how that exposure varies with dose; they are not, by themselves, evidence of improvement in NASH or of a clinical benefit.

The sampling schedule included pre-dose and post-dose measurements on Day 29, along with measurements at specified times on Day 1, Day 30, and Day 85. The record specifies that Cmax was defined as the maximum observed concentration. The primary-outcome summary is described in terms of a mean and standard deviation, which would describe the central value and the spread of participant measurements if results were posted.

The registry record does not report Cmax values, standard deviations, participant counts contributing to each result, or a dose-group comparison. It therefore does not establish the magnitude or precision of exposure at either dose, nor whether observed concentrations differed between groups. The PK population definition excludes participants whose protocol deviations or adverse events significantly affected pharmacokinetics and requires at least one post-dose sample, so results for that population would not automatically represent every randomized participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying what was measured, in whom, and at what times. In this study, the primary measure was Cmax for elafibranor and GFT1007. Concentration is a continuous measurement, so a mean can describe the average observed value and a standard deviation can describe how dispersed observations are around that average. Neither statistic is posted for the primary outcome in the registry record, so they cannot be interpreted for this study.

What does a mean and standard deviation describe?

As a general statistical explanation, a mean summarizes the center of a set of continuous observations. A standard deviation describes variation among those observations in the same measurement units. The mean alone does not show whether observations were tightly grouped or widely spread; the standard deviation adds information about that spread. These summaries are most informative when the number of observations and the analysis population are also clear. The registry record specifies the intended summary format but does not report the corresponding Cmax results or the number contributing to each summary.

Why does the sampling schedule matter?

Cmax depends on the concentrations actually measured and the timing of those measurements. A maximum observed concentration is the largest value captured in the sampled profile; it is not necessarily the exact biological peak if the sampling schedule does not capture that point. The registered schedule includes multiple post-dose collection times on Day 29 and later measurements on Day 30 and Day 85. That structure is relevant to interpreting exposure, but the record does not report individual concentration profiles, missing samples, or the method used to handle values that were not observed.

What is a dose-group comparison?

A comparison between the 80 mg and 120 mg groups would quantify how the observed endpoint differs between assigned doses. Statistical uncertainty around a comparison is commonly expressed with a confidence interval. As a general explanation, a confidence interval describes a range of values compatible with the data and the specified statistical method; it reflects precision as well as the estimate itself. The registry record does not post a dose contrast, confidence interval, or test result for Cmax. It is therefore not possible to assess the size or precision of a difference.

Why do small groups affect precision?

As a general principle, estimates based on few observations tend to be less precise than estimates based on more observations, especially when individual measurements vary. The enrollment of 10 indicates that the overall study was small, but the count contributing to each PK outcome is not reported. The safety record lists 5 participants at risk in each group, which should not be substituted for the PK analysis count. Without the outcome-specific counts and variability, the precision of any pharmacokinetic estimate cannot be evaluated.

What is over-dispersion?

As a general explanation, over-dispersion occurs when observed variation is greater than a statistical model expects. It matters because a model that understates variability can produce confidence intervals that are too narrow and tests that appear more conclusive than warranted. The posted record does not identify a model for the primary endpoint, report a dispersion assessment, or provide data that would allow over-dispersion to be evaluated. Because the primary outcome is summarized as a mean with standard deviation, it is not appropriate to assert that a particular model or variance adjustment was used.

How should planning calculations be understood?

As a general explanation, sample-size planning uses assumptions about the outcome, variability, allocation, and target effect to illustrate the amount of information a study might need. Such calculations are not results from participants and do not establish the power actually achieved. The registry record does not report the trial's own sample-size justification. Any planning illustration based on an observed effect is a separate, assumption-dependent calculation; it cannot be treated as the trial's original design rationale or as observed power.

The registry record does not report whether interim analyses were planned or conducted, how missing measurements were handled, or which statistical tests or models were prespecified. Those details matter because analysis choices can affect estimates and uncertainty, especially with a small study and repeated measurements. In their absence, interpretation should stay with the registered design and the results actually posted: enrollment and safety counts are available, while primary and secondary outcome analyses are not.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a broad set of secondary pharmacodynamic outcomes, including liver enzymes, other liver markers, and fasting plasma glucose measured at scheduled visits. Testing many markers and time points raises a general multiplicity concern: the more statistical comparisons made, the greater the chance that some may appear notable by chance alone. A prespecified hierarchy, adjustment method, or distinction between confirmatory and exploratory analyses can help readers interpret such results. These analysis details are not reported in the registry record, and no outcome analyses are posted.

Missing-data handling is also not reported. The study schedule includes repeated measurements, but the record does not state how absent samples or incomplete follow-up were treated in the planned analyses. It does not report the number of observations available for each marker and visit. Without this information, the effect of incomplete measurement on estimates cannot be assessed.

The registry describes a PK population requiring at least 1 study-drug dose and at least 1 post-dose PK sample, while excluding participants with protocol deviations or adverse events that significantly affected PK. The number in that population is not reported. The record does not describe an intention-to-treat analysis population or explain how randomized participants who did not meet the PK criteria were handled for other outcomes.

The statistical analysis plan, any interim analyses, and multiplicity adjustments are not reported in the registry record. No assumption about these procedures is warranted. These omissions, together with the absence of posted outcome analyses, prevent evaluation of outcome-specific denominators, missingness, and the interpretation of any potential findings across the many registered measures.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists 5 participants at risk in the elafibranor 80 mg group and 5 in the 120 mg group. It records 0 serious adverse events in each group and 0 deaths in each group. For other adverse events, the record lists 2 affected participants in the 80 mg group and 0 in the 120 mg group.

These are participant counts, not event rates calculated for comparison. The record does not report the terms of the other adverse events, their severity, timing, duration, or whether investigators considered them related to elafibranor. It also does not describe the observation time for each participant or provide a detailed account of adverse-event collection. The registry's serious-event terms list is empty, so specific serious-event descriptions are not reported in the registry record.

Zero recorded serious adverse events or deaths in a small study does not establish that such events cannot occur. Likewise, the difference in other-adverse-event counts should not be interpreted as evidence that one dose is safer: the counts are small, event details are absent, and the registry does not report a comparative safety analysis. These figures describe what is posted, not a complete estimate of risk.

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

The registry record establishes that a randomized, open-label phase 2 study was designed to assess elafibranor pharmacokinetics, pharmacodynamics, safety, and tolerability in children and adolescents 8 to 17 years of age with NASH. It identifies two once-daily dose groups, 80 mg and 120 mg, and describes a 12-week treatment period. It also provides a primary endpoint definition and scheduled PK sampling times.

What the record does not establish is the primary outcome result. No mean Cmax values, standard deviations, dose comparison, or statistical uncertainty are posted. Nor are results reported for the registered secondary liver-marker and glucose outcomes. The absence of those results means the registry entry cannot show whether exposure differed by dose or whether measured biological markers changed during the study.

The safety entries are limited to participant counts: no serious adverse events or deaths are listed in either group; other adverse events are listed for 2 participants in the 80 mg group and none in the 120 mg group. Event descriptions and comparative analyses are not reported. These counts should not be taken as proof of safety or as evidence of a difference between doses.

The study's terminated status is recorded, but the reason is not reported in the registry record. Termination alone does not explain whether the study ended early, whether planned assessments were completed, or why outcome analyses are absent. Enrollment of 10 and the lack of posted analyses constrain what can be learned from this record.

In short, the record documents a study design and limited safety counts, not a complete set of findings. It does not permit conclusions about NASH improvement, clinical benefit, dose selection, or comparative safety. Those questions would require reported outcome data and sufficient information about analysis populations, missing measurements, and statistical methods.

13. Why This Trial Matters Statistically

This trial is statistically notable because it asks a pharmacokinetic question in a pediatric population using a randomized comparison of two active dose levels. Drug concentration measurements can characterize exposure, while the associated pharmacodynamic outcomes can describe changes in biological markers. Keeping these questions distinct is important: a pharmacokinetic endpoint measures drug concentration, whereas a marker change or clinical outcome addresses a different aspect of the study.

The design also illustrates why registration details alone are not equivalent to analyzable results. The registry specifies a Cmax endpoint, a concentration unit, a summary format, and sampling times. Those details clarify what the investigators intended to measure, but the absence of endpoint values and analyses means readers cannot evaluate the observed exposure or its precision. The distinction between a defined endpoint and a reported result is central to evidence appraisal.

The listed PK population criteria are another important statistical feature. A PK analysis based on participants meeting post-dose sampling and data-quality criteria may differ from a population defined by randomization. Knowing the analysis population and its size is necessary to interpret estimates and understand who contributed data. The record gives the criteria but not the number meeting them.

The many registered secondary outcomes also raise the general issue of multiplicity. Multiple markers and assessment times can create many possible comparisons, making a prespecified analysis strategy important. That strategy and the results are not reported. Finally, the small enrollment and sparse safety counts make descriptive restraint essential: counts can be stated, but they cannot support precise comparative safety conclusions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation of the registry record is the absence of posted primary and secondary outcome results. Although the primary endpoint and measurement schedule are described, no Cmax values, standard deviations, outcome-specific sample counts, or dose comparisons are reported. The listed secondary outcomes likewise have no posted analyses. This prevents assessment of estimates, variability, and precision.

Enrollment was 10, and the registry lists 5 participants at risk in each group for safety. The PK analysis population has additional criteria, but its size is not reported. The record does not say how many randomized participants completed treatment or contributed each scheduled measurement. The effect of missing or unusable samples therefore cannot be evaluated.

The study was open label and had no masking. The record does not describe assay methods, laboratory quality controls, adherence, or procedures for handling protocol deviations beyond the PK population definition. It does not report the reason for termination or whether the planned follow-up and assessments were completed.

Important analysis details are also absent: the sample-size justification, statistical tests or models, handling of repeated measurements, missing-data procedures, multiplicity strategy, and any interim analyses are not reported in the registry record. Without those details, even posted estimates would be harder to interpret; without the estimates themselves, the study's pharmacokinetic and pharmacodynamic findings cannot be assessed from this record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH) — NCT03883607.
• Registry record last updated 2021-10-28; status last verified 2021-09.
• Results first posted 2021-10-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03883607 is a randomized, open-label, parallel-group phase 2 study of elafibranor in children and adolescents 8 to 17 years of age with NASH. It compared once-daily 80 mg and 120 mg doses over 12 weeks. Enrollment was 10, and the registry lists the study as terminated.

The primary endpoint was maximum observed plasma concentration of elafibranor and GFT1007. Pharmacodynamic outcomes included liver markers and fasting plasma glucose. The registry record does not report primary or secondary outcome analyses, the reason for termination, a sample-size justification, or detailed statistical methods.

The safety record lists no serious adverse events or deaths in either group. Other adverse events are listed for 2 participants in the 80 mg group and none in the 120 mg group. Event details are not reported.