Evaluation of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis (CF) Participants 12 to Less Than 24 Months of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis (CF) Participants 12 to Less Than 24 Months of Age (NCT05882357), a non-randomized phase 3 study. The primary outcome is Part A: Observed Pre-dose Concentration (Ctrough) of ELX, TEZ, IVA, and Their Relevant Metabolites (M23-ELX, M1-TEX, M1-IVA).

2. Clinical Question

In addition to pharmacokinetics, the study description names safety, tolerability, pharmacodynamics, and efficacy as areas of evaluation. The listed secondary outcomes include Part B pre-dose concentrations and change in sweat chloride through Week 24. The registry record gives outcome titles but no numerical results for those outcomes. Accordingly, the available information describes what the study set out to measure and reports selected safety counts; it does not establish a comparative treatment effect.

3. Trial Design

This is a Phase 3, open-label study with non-randomized allocation and a sequential model. It is marked completed and records enrollment of 67 participants. The registry dates are a start date of 2023-06-27 and a primary completion date of 2025-09-04. No randomized comparator is identified, and the record explicitly cautions that the arms are not a like-for-like control comparison.

The study has two described parts. In Part A, participants received ELX 40 mg, TEZ 20 mg, and IVA 30 mg as fixed-dose combination granules once every morning, plus 25 mg IVA once every evening, for 15 Days. Part B is also described as ELX/TEZ/IVA, with one of three dosing regimens selected based on body weight at Day 1. The Part B regimen description ends partway through its third dosage, so the complete dosing details are not reported in the registry record. IVA is also listed separately as an intervention, but the registry material does not clarify a separate comparison involving it.

Open-label means the study is not described as masked. In general, this can matter when outcomes involve subjective assessment or care decisions. The primary outcome is a concentration measure, but the registry record does not report how laboratory assessments were conducted or whether assessors were independent. Non-randomized sequential parts also do not support a simple causal comparison between Part A and Part B: assignment was not randomized, and the parts have different descriptions and purposes.

The total enrollment should not be mistaken for the number in either part or for the PK analysis population. The safety records give 15 participants at risk in Part A and 54 in Part B, while the primary population is defined by receipt of at least one dose. The record does not give additional participant-flow details, exclusions, or the number contributing to each concentration estimate.

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: Baseline characteristics were analyzed based on participants who received at least one dose of study drug, resulting in 69 (15 Part A +54 Part B) dosed participant records across both study parts.

Part A (15 Days)

Part B (24 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PK set included participants who received at least 1 dose of study drug.

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: All participants who are enrolled (defined as participants having data in the clinical database) and carry the intended CFTR allele mutation and received at least 1 dose of study drug were included in the baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Observed Pre-dose Concentration (Ctrough) of ELX, TEZ, IVA, and Their Relevant Metabolites (M23-ELX, M1-TEX, M1-IVA), measured over At Day 15.

The primary endpoint is the observed pre-dose concentration, or Ctrough, of ELX, TEZ, IVA, and their relevant metabolites in Part A at Day 15. The listed metabolites are M23-ELX, M1-TEX, and M1-IVA. The spelling M1-TEX appears in the primary endpoint title, whereas a secondary outcome uses M1-TEZ; the registry record does not explain this difference in labeling.

A pre-dose concentration is measured before a subsequent dose, and pharmacokinetic assessments use such measurements to characterize drug exposure over a dosing interval. In general, concentration data help describe how much drug or metabolite is present at a specified sampling time. They are not, by themselves, direct measures of clinical benefit. The record identifies the reported summary measure as a median with standard deviation as the dispersion measure, and gives micrograms per milliliter as the unit.

The stated PK set includes participants who received at least one dose of study drug. That definition identifies the intended analysis population, but the record does not give the number contributing to the primary endpoint or explain how measurements below assay limits, missing samples, or repeated observations were handled. Most importantly, no median concentrations or standard deviations are reported in the registry record. The endpoint’s purpose and measurement time can therefore be described, but its numerical result and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint measure?

The primary endpoint is a set of pre-dose drug and metabolite concentration measurements in Part A at Day 15. In pharmacokinetics, a pre-dose or trough measurement is obtained before a scheduled dose. In general, this timing can help characterize exposure near the end of a dosing interval. It does not directly measure a participant’s symptoms, lung function, or another clinical outcome. The unit is microgram per milliliter, and the registry identifies the median as the summary measure with standard deviation as the dispersion measure.

The PK set is defined as participants who received at least one dose of study drug. This is an analysis-population definition, not a statement about how many participants had usable Day 15 samples. The number contributing to each concentration estimate is not reported in the registry record. The record also does not explain the assay, sample handling, concentration transformations, or rules for values that could not be quantified. These details matter for understanding how measurements become reported summaries, but they cannot be inferred from the endpoint title.

How should medians and dispersion be understood?

In general, the median describes the central position of observed values and is less influenced by extreme observations than the arithmetic mean. A standard deviation describes spread around a mean; it is commonly used to summarize variability when values are treated on an appropriate scale and distributional assumptions are suitable. The registry’s use of a median together with standard deviation is the stated summary specification, but no numerical estimate is posted. The record does not explain whether the standard deviation is calculated on the original or transformed scale, or how the two summaries are intended to be interpreted together.

A confidence interval, when reported, expresses uncertainty around an estimate under a specified statistical procedure. It is not a range that guarantees the true value lies within its bounds. No confidence interval for the primary endpoint is reported. Without an estimate, a precision interval, and the number of observations contributing to it, readers cannot assess the magnitude or statistical precision of the concentration summaries.

What does the study structure permit?

Allocation is identified as non-randomized, masking as none, and the model as sequential. In general, random assignment helps balance both measured and unmeasured characteristics across comparison groups, while masking can reduce the influence of expectations on some study processes. Neither feature is described for this study. The registry therefore does not support treating Part A and Part B as randomized comparators. Their different roles and dosing descriptions should be kept distinct rather than combined into a head-to-head claim.

The study is open-label. For objective laboratory measurements, the potential for subjective assessment may differ from that for symptom or clinician-rated outcomes, but the record does not describe laboratory blinding or independent assessment. It would be speculative to assume either was or was not used. The protocol’s allocation procedures, detailed analysis plan, and any planned comparisons are not reported in the registry record.

How should safety counts be read?

The safety groups list the number at risk, the number affected by serious adverse events, the number affected by other adverse events, and deaths. These are participant counts within Part A and Part B. In general, an affected-participant count differs from an event count: one participant may experience multiple events, while the affected count records whether a participant had at least one event in the category. The registry does not provide enough detail to reconstruct event counts, event timing, duration, severity beyond the serious classification, or causal attribution.

The serious adverse event terms and percentages are registry listings. The denominator and event-counting basis for each term are not separately explained in the record. They should not be combined with the affected-participant totals or interpreted as a comparative measure between study parts. The counts are descriptive and do not establish that study drug caused an event.

What are the planning assumptions?

The registry’s sample-size assumptions describe planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. In general, a significance level sets a threshold for a statistical test under its assumptions; equal allocation and a normal approximation are modeling choices for a planning calculation. The registry also distinguishes the type of quantity used for time-to-event planning from other planning calculations. These assumptions do not describe the trial’s own design justification, and the record does not report that justification.

Planning calculations are not observed power and do not establish the probability that a trial result is true. They also cannot remedy the absence of a randomized comparator or replace the missing endpoint estimates. The record does not report the effect estimates needed to evaluate any such illustration, nor does it report a formal statistical analysis of the primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and secondary outcomes, but it does not describe a multiplicity strategy. Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, conducting multiple tests can increase the chance of at least one apparently notable result if no adjustment or hierarchy is specified. The record does not state whether endpoints were tested formally, whether any testing hierarchy was planned, or whether adjustments were made. It therefore does not support claims about control of a family-wise error rate or another multiplicity criterion.

Missing-data handling is also not reported in the registry record. The primary population includes participants who received at least one dose, but that does not state how many had a Day 15 concentration measurement or how missing samples were treated. The record does not describe imputation, exclusion rules, sensitivity analyses, or reasons for missing observations. For the secondary outcome of change in sweat chloride from baseline through Week 24, it does not report the available measurement counts or missing-data methods.

The record identifies a PK set for the primary endpoint, but does not give a complete account of analysis populations for all outcomes. It does not report whether there were safety, per-protocol, or other analysis sets beyond the group counts. Nor does it provide a statistical analysis plan, a detailed participant flow, or outcome-level estimates. The absence of these details limits assessment of how missing observations, multiple outcomes, and analysis-population choices may affect interpretation. These are reporting gaps; they do not establish that particular methods were or were not used outside what the registry record states.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infective pulmonary exacerbation of cystic fibrosis (7.4%), respiratory syncytial virus infection (1.9%), viral upper respiratory tract infection (1.9%), pseudomonas test positive (1.9%).

The safety record lists Part A with 15 participants at risk and Part B with 54. Serious adverse events affected 0 participants in Part A and 6 in Part B. Other adverse events affected 14 participants in Part A and 53 in Part B. Deaths are listed as 0 in each part. These counts describe the recorded groups and should be read separately by category.

“Affected” refers to participants with an event in the listed category; it is not necessarily the number of individual event occurrences. A participant can experience more than one event, and the registry record does not provide the full event-level data needed to determine counts, timing, duration, or recurrence. The serious-event terms listed include infective pulmonary exacerbation of cystic fibrosis at 7.4%, respiratory syncytial virus infection at 1.9%, viral upper respiratory tract infection at 1.9%, and Pseudomonas test positive at 1.9%.

These figures are descriptive, not a randomized comparison. The study parts are non-randomized and are not identified as like-for-like control groups. The counts cannot establish that an event was caused by treatment, and they do not by themselves characterize clinical severity beyond the serious-event classification. The registry record does not give additional information about attribution or event-level context.

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

The record supports a description of a Phase 3, open-label, non-randomized study of ELX/TEZ/IVA in participants with cystic fibrosis, with two study parts and a primary pharmacokinetic endpoint in Part A. It also supports reporting the listed safety counts and the titles of secondary outcomes. It does not include numerical estimates for the primary concentration endpoint, so no conclusion about the size or precision of the measured concentrations can be drawn from the posted results.

The study is not described as a randomized comparison, and the registry explicitly notes that the arms are not like-for-like control groups. Consequently, Part A and Part B should not be treated as treatment and control arms in a causal comparison. Non-randomized study-part counts can describe what was recorded in each part, but they do not isolate a treatment effect from differences in participants, dosing, timing, or study context.

The primary endpoint is pharmacokinetic rather than a direct clinical outcome. In general, concentration data provide information about drug exposure at a defined sampling time. They do not, without additional evidence, establish clinical benefit or harm. The brief summary mentions pharmacodynamics and efficacy, and a secondary outcome concerns change in sweat chloride through Week 24, but numerical results for those measures are not reported in the registry record.

The safety listings indicate that serious adverse events and other adverse events were recorded in the study groups, and that no deaths are listed. These registry entries do not establish causation or comparative risk. The record also does not provide enough event-level detail to assess timing, recurrence, or attribution. Any interpretation should remain descriptive and bounded by the reported counts.

In short, the record describes the study framework and selected safety observations but does not furnish the primary numerical results needed to quantify the pharmacokinetic endpoint. It cannot establish a treatment effect, a benefit-risk conclusion, or a comparison against an untreated or randomized control group. Those conclusions would require evidence beyond the information reported in this registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a pharmacokinetic objective and a clinical treatment comparison. Its primary endpoint focuses on pre-dose concentrations of ELX, TEZ, IVA, and metabolites, rather than a direct clinical outcome. Such measurements can be useful for characterizing exposure, but the statistical meaning of a concentration summary depends on the observations, variability, and analysis details. The registry record names the summary approach but does not report the actual estimates.

The non-randomized, sequential structure also matters. Part A and Part B are not interchangeable arms of a controlled comparison: Part B dosing is based on body weight, and the parts have different descriptions. This makes it important to distinguish descriptive summaries from comparative inference. Counts from both parts can document what the record reports, but they cannot by themselves answer what would have occurred under an alternative treatment or control condition.

The endpoint and population definitions illustrate why analysis-set details matter. The primary PK set includes participants who received at least one dose, while the safety listings give group sizes at risk. The number with usable endpoint measurements is not reported. Without that information and corresponding estimates of uncertainty, readers cannot assess how complete or precise the concentration summaries are.

Finally, the record names several domains of evaluation, including safety, pharmacodynamics, and efficacy, but posts no numerical results for the primary endpoint or listed secondary outcomes. This gap is central to interpretation: a completed study status and an endpoint description are not substitutes for outcome estimates. The statistically appropriate reading separates the design and descriptive safety counts from claims about treatment effects that the registry record does not establish.

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.

Several limitations are specific to the information recorded for this study. First, the registry title and official title identify participants 12 to less than 24 months of age, while the brief summary says 2 to less than 24 months. The lower age limit is therefore inconsistent in the record. The listed Part B dosing text is also incomplete, ending during the description of the third regimen. The complete regimen details cannot be established from the record.

Second, the primary endpoint title spells one metabolite as M1-TEX, while a secondary outcome uses M1-TEZ. The record does not explain whether these labels refer to the same analyte or reflect different terminology. The primary endpoint’s numerical concentrations and dispersion are not reported, and neither are numerical results for the listed secondary outcomes. The endpoint population is defined, but the number contributing measurements and the handling of missing samples are not stated.

Third, the study is open-label, non-randomized, and sequential, with no like-for-like randomized control comparison. This limits causal interpretation of differences between study parts. The registry does not describe masking of laboratory assessments, detailed allocation procedures, or a statistical analysis plan. It also does not report multiplicity procedures, missing-data methods, detailed participant flow, or the protocol’s sample-size justification.

Finally, the safety information is presented as group-level affected-participant counts and selected serious-event terms. Event-level context, attribution, and detailed timing are not reported. These limitations do not show that particular methods were absent from study conduct; they identify details not reported in the registry record and therefore unavailable for evaluating the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis (CF) Participants 12 to Less Than 24 Months of Age — NCT05882357.
• Registry record last updated 2026-10-15; status last verified 2026-10.
• Results first posted 2026-10-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed Phase 3, open-label, non-randomized sequential study of ELX/TEZ/IVA in cystic fibrosis, with enrollment of 67 participants. The title gives an age range of 12 to less than 24 months, although the brief summary gives a different lower age limit. Part A assessed pre-dose concentrations at Day 15; Part B used body-weight-based dosing and included listed secondary outcomes through Week 24.

The primary endpoint is summarized in the record as a median with standard deviation, but no numerical endpoint results are reported. Selected safety counts include serious adverse events affecting 0 of 15 participants in Part A and 6 of 54 in Part B, with 0 deaths listed in each part. Because allocation was non-randomized and the parts are not like-for-like control groups, the counts are descriptive rather than a controlled treatment comparison. The record does not report detailed analysis methods, missing-data handling, or numerical secondary outcome results.