A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del (NCT04105972), a randomized phase 3 study. The primary outcome is Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score.

2. Clinical Question

The clinical question is specifically about the reported patient-reported respiratory score in this trial population and over this treatment period. It is not a comparison with no treatment: both groups received active combination regimens, and both had the TEZ/IVA run-in. The posted primary result therefore describes the contrast between adding ELX to the TEZ/IVA regimen and continuing TEZ/IVA under the study conditions. The record also lists lung function, sweat chloride and safety outcomes, but these are secondary to the prespecified primary question in the registry record. The size and precision of the primary contrast can be read from the estimated difference and its confidence interval, while the design and analysis details determine how that contrast should be interpreted.

3. Trial Design

This was a Phase 3b, randomized, double-blind, controlled, parallel-group study. The registry lists enrollment of 176 participants. The two reported treatment groups were TEZ/IVA and ELX/TEZ/IVA; the primary outcome results include 88 participants in the TEZ/IVA group and 87 in the ELX/TEZ/IVA group. The primary analysis population is described as randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug in the treatment period.

Both groups had a 4-week TEZ/IVA run-in before the 24-week treatment period. During that treatment period, one group continued TEZ/IVA and the other received ELX/TEZ/IVA. The study began on 2019-10-03, had a primary completion date of 2020-07-24, and is listed as completed. The registry describes masking as quadruple; the identities of all parties covered by that masking are not reported in the registry record.

The design supports a comparison between the two assigned regimens in the randomized study population. It does not describe a comparison against an untreated group. Although IVA is listed among the interventions, the reported primary comparison is between the two combination regimens. The registry record does not report the original sample-size justification, allocation ratio, details of the randomization procedure, or the planned analysis population beyond the primary population definition. Those details should not be inferred from the observed group sizes or the planning illustrations.

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: This study was conducted in cystic fibrosis (CF) participants aged 12 years or older.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomized participants who carried the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in treatment 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 Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score, measured over From Baseline Through Week 24.

The primary endpoint was absolute change in the CF Questionnaire-Revised respiratory domain score from baseline through Week 24. The CFQ-R is described in the registry as a validated participant-reported measure of health-related quality of life for people with cystic fibrosis. Its respiratory domain assesses respiratory symptoms. Scores range from 0 to 100, and higher scores indicate fewer symptoms and better health-related quality of life.

A participant-reported measure can capture how symptoms are experienced, rather than relying only on a physiological measurement. In this trial, the endpoint therefore addresses the respiratory symptom and health-related quality-of-life dimension represented by the questionnaire. It is a continuous outcome: the analysis estimates average score change rather than counting participants who cross a threshold. The registry reports least-squares mean changes for each group and a least-squares mean difference between groups.

The primary time point is described as change from baseline through Week 24. The registry does not give a threshold for a change considered important to participants, nor does it report how baseline scores were distributed. Consequently, the magnitude and precision of the group contrast can be described statistically, but the registry record alone does not establish what score difference participants would consider meaningful.

7. Results Posted in the Registry

• ELX/TEZ/IVA: mean 17.10 versus 1.20 on control; difference 15.90 (95% CI 11.74 to 20.06), standardized effect d = 1.13; z-test p = <0.001.

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.

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

• 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 errors.
• Result:
  • ELX/TEZ/IVA: mean 11.20 versus 1.00 on control; difference 10.20 (95% CI 8.26 to 12.14), standardized effect d = 1.56; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for ELX/TEZ/IVA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Absolute Change in Sweat Chloride (SwCl)

• 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 errors.
• Result:
  • ELX/TEZ/IVA: mean -46.20 versus -3.40 on control; difference -42.80 (95% CI -46.27 to -39.33), standardized effect d = -3.66; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for ELX/TEZ/IVA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary results follow a directionally coherent pattern across the two reported continuous measures: the ELX/TEZ/IVA group had a higher estimated ppFEV1 change and a more negative estimated sweat chloride change than the TEZ/IVA group. These measures address different aspects of the study outcomes from the participant-reported respiratory score. Their pattern can be considered alongside the primary result, but it does not make them interchangeable measures or independently establish the meaning of the primary score contrast.

The registry reports a sponsor analysis for ppFEV1 with a confidence interval and p-value, and reports a sponsor contrast and confidence interval for sweat chloride without a p-value in the record. The simple recalculations for the secondary outcomes are unadjusted. As requested for interpretation, the endpoint-specific estimates and intervals are best read with their own displays rather than repeated as a second list of results.

In general, multiple outcomes create multiple opportunities to observe nominally unusual results. If several outcomes are tested, unadjusted p-values do not account for that multiplicity. A result that appears statistically persuasive on its own may provide less confirmatory evidence when it is one of several analyses, especially if no adjustment or hierarchy was planned. The registry record does not report a multiplicity strategy for the secondary outcomes, so their p-values should not be treated as if family-wise error or false discovery had been controlled.

Secondary findings can add context and help describe whether related outcomes point in a similar or different direction. They should not be used to overrule the primary endpoint or to claim a broader conclusion than the record supports. The statistical weight of each secondary result depends on its prespecified status, analysis plan, measurement properties and multiplicity handling; those details are not reported in the registry record. The displayed estimates describe the posted outcomes, while their confirmatory status remains uncertain from the available record.

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

• Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
• Absolute Change in Sweat Chloride (SwCl)
• Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, because it is a score measured on a numerical scale. The registry reports least-squares means for the two treatment groups and a least-squares mean difference. A least-squares mean is a model-based group estimate; unlike a simple arithmetic average, it can reflect the structure and terms of the fitted model. The registry's primary analysis method is a Mixed-effects Model for Repeated Measure.

What does a repeated-measures model do?

In general, repeated-measures methods analyze observations taken at multiple time points while accounting for the fact that observations from the same participant are related. A mixed-effects model can represent both average patterns across participants and variation among participants. The sponsor's reported primary method is identified as a repeated-measures model, but the registry record does not report its full specification, including the covariance structure, fixed effects, handling of baseline values, or other model terms. Those details should not be reconstructed from the reported endpoint summary.

What does the least-squares mean difference express?

The reported contrast is the model-based difference between the treatment-group estimates for the endpoint. Its unit is CFQ-R score units. The registry reports 15.9 as the estimate and a 95% confidence interval from 11.7 to 20.1. A positive contrast corresponds to a higher estimated score for ELX/TEZ/IVA than TEZ/IVA, consistent with the score direction in which higher values indicate fewer symptoms and better health-related quality of life. The estimate describes an average contrast and does not say that every participant had the same outcome.

How should the p-value be understood?

In general, a p-value measures how incompatible the observed data, or data more extreme, are with a specified null model. It is not the probability that the null hypothesis is true and it does not measure the size or importance of an effect. The registry reports p < 0.001 for the primary analysis. This is evidence against a zero-difference null under the reported analysis, but the p-value does not address all questions about model validity, generalizability or clinical importance.

Why distinguish standard errors from standard deviations?

The registry labels the dispersion accompanying the group least-squares means as a standard error. In general, a standard error describes the precision of an estimated mean, while a standard deviation describes the spread of individual observations. They are not interchangeable. The simple recalculation uses an approximate pooled standard deviation derived from the posted standard errors and group sizes; the registry labels that approximation as such. It is not a participant-level estimate of variability and should not be confused with the sponsor's model-based analysis.

The simple recalculated contrast is unadjusted and based on posted summary statistics. Its p-value is reported as p < 0.001. The sponsor's analysis is the registry's repeated-measures result and should be read as the primary inferential analysis. The two displays serve different purposes: one reports the study's model-based result, while the other offers a transparent, simple comparison based on aggregate values. Neither the recalculation nor the planning illustrations can reconstruct participant-level data or omitted model details.

For secondary continuous outcomes, the registry also reports least-squares means, standard errors and between-group contrasts. The ppFEV1 analysis is identified as using a Mixed-effects Model for Repeated Measure. The analysis method for sweat chloride is not reported in the registry record. General statistical principles about repeated observations apply only to the extent that the method was used as described; no unreported modeling details should be assumed.

11. Confidence Intervals and Precision

The primary 95% confidence interval is 11.7 to 20.1 units for the reported mean difference. In general, a confidence interval conveys the uncertainty around an estimate: intervals that are narrower indicate greater statistical precision than wider intervals, given the model and data. The interval is entirely above zero, so the reported primary result is inconsistent with a zero difference at the conventional two-sided 5% level under the fitted analysis. Its width still matters: the data are compatible with a range of positive contrasts, not just the point estimate of 15.9.

The interval does not mean there is a 95% probability that the true effect lies within these particular bounds. In repeated-sampling terms, the method is designed to produce intervals covering the underlying parameter at the stated rate when its assumptions hold. The registry does not provide enough information to evaluate every model assumption or the effect of missing observations. The confidence interval should therefore be read as conditional on the analysis method and its assumptions.

The primary result is reported with one decimal place for the confidence limits. The simple recalculation gives a separate interval of 11.74 to 20.06, but the sponsor's reported model-based interval is the principal interval for interpreting the trial's primary analysis. These intervals arise from different approaches and should not be treated as independent confirmations. The calculated interval from summary statistics does not capture all features of the repeated-measures model.

Precision is distinct from importance. A narrow interval can estimate an effect precisely without establishing whether its size matters to participants; a wide interval can leave substantial uncertainty even when a point estimate appears large. No clinically important difference threshold is reported for the CFQ-R respiratory domain in this registry record, so the confidence interval alone cannot classify the whole range as meaningful or unimportant.

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 table and curve are planning illustrations based on the observed effect, not the trial's original design calculations. The figures are participants per arm because these are continuous outcomes, not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the selected effect under those assumptions, if that effect is the true one. The 90% power column gives the corresponding per-arm count for a design targeting 90% power. These are prospective planning concepts, not statements about what the completed trial actually had power to detect. The displayed counts are illustrations, not a reconstruction of the enrollment decision.

The rows that plan for 100%, 75% and 50% of the observed effect show how the assumed effect size changes the planning count. Smaller effects need more participants to detect under otherwise unchanged assumptions. For example, the primary endpoint illustration at 100% of the observed effect lists 13 participants per arm for 80% power and 17 for 90% power; at 50% of the observed effect it lists 49 and 66 per arm, respectively. This is not observed power. The calculations rely on the observed effect and simplified assumptions and should not be used as evidence that the completed trial was adequately or inadequately powered.

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 = 15.900; pooled standard deviation σ = 14.031.
2. n = 2 × (1.96 + 0.842)² × 14.031² / 15.900² = 12.2, rounded up to 13 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 <- 15.9                      # observed difference in means
sigma <- 14.0314469278893                     # 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(4105972)
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 = 13 (80% power), 17 (90% power)
 75% of observed effect: n per arm = 22 (80% power), 30 (90% power)
 50% of observed effect: n per arm = 49 (80% power), 66 (90% power)
power.t.test: 13.3 
Simulated power at n = 13 per arm: 0.790 (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. Analyses Reported by the Sponsor

The sponsor's reported primary analysis is a Mixed-effects Model for Repeated Measure. It gives a least-squares mean difference of 15.9, a 95% confidence interval from 11.7 to 20.1, and p < 0.001. The posted group means are 17.1 for ELX/TEZ/IVA and 1.2 for TEZ/IVA.

The simple recalculation from the posted summary statistics also gives a mean difference of 15.9, with an unadjusted p < 0.001. Its confidence limits are 11.74 to 20.06; the sponsor's model-based interval is reported at one decimal place. The registry does not flag a discrepancy. This close numerical correspondence is not a reason to treat the aggregate recalculation as the sponsor's model, since the methods differ and the recalculation cannot represent all details of repeated observations.

The sponsor's analysis is the trial's reported inferential result. The recalculation is useful as a plain aggregate check, but it does not replace the repeated-measures model or reveal its unreported specifications. For the primary interpretation, the sponsor-reported estimate, interval and p-value take precedence as the posted trial analysis. The registry does not report further details needed to independently reproduce that model.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, time points, groups or analyses. In general, the more statistical tests considered, the greater the chance that at least one will cross a conventional significance threshold by chance if all null hypotheses are true. A prespecified testing hierarchy or adjustment can address this issue, but the registry record does not report whether such a strategy was used for the primary and secondary outcomes. The secondary results therefore should not be interpreted as multiplicity-adjusted unless that is explicitly stated in the record.

The primary outcome is identified, which helps distinguish the main reported question from secondary measures. However, the registry does not report details about interim analyses, stopping rules, or any adjustments for repeated looks at the data. It also does not report a full statistical analysis plan, including all covariates, model specifications, sensitivity analyses or criteria for selecting analyses. The absence of these details in the registry should not be filled in by assumption.

The primary analysis population is defined as the full analysis set of randomized participants with the intended CFTR allele mutation who received at least 1 dose of study drug in the treatment period. The registry does not state how many participants were excluded from that set, whether all randomized participants were included in each endpoint analysis, or how missing endpoint observations were handled. These details matter because missingness can affect the estimated contrast if the participants with observed data differ systematically from those without observed data.

In general, repeated-measures models can use available observations under assumptions about the relationship between missingness and observed data. That general property does not establish which missing-data assumptions were made in this trial. The registry record does not report imputation methods, reasons for missing data, sensitivity analyses for missingness, or outcome-specific analysis populations. Consequently, the posted estimates can be described, but the robustness of those estimates to missing-data choices cannot be assessed from this record alone.

The record gives enrollment of 176 and primary outcome group counts of 88 and 87. The registry does not explain the difference between the enrollment total and the sum of those outcome counts. It is not appropriate to infer a reason from those figures alone. Full participant disposition and outcome-specific missingness information are not reported in the registry record.

16. 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 (10.2%), thrombocytopenia (1.1%), alanine aminotransferase increased (1.1%), type 3 diabetes mellitus (1.1%), anxiety (1.1%).

The registry reports serious adverse events in 14 of 88 participants in the TEZ/IVA group and 5 of 87 in the ELX/TEZ/IVA group. It reports other adverse events in 72 of 88 and 59 of 87 participants, respectively. Deaths are listed as 0 in both groups. These are participant counts, not estimates of comparative risk adjusted for follow-up or other factors.

Serious adverse events and other adverse events are distinct reported categories; the counts should not be combined. The record lists infective pulmonary exacerbation of cystic fibrosis at 10.2% among the serious-event terms, and also lists thrombocytopenia, alanine aminotransferase increased, type 3 diabetes mellitus, anxiety and depression at 1.1% each. The denominator and event-term reporting details for these percentages are not stated in the record, so they should not be converted into participant counts or compared as though their denominators were confirmed.

These summaries describe events recorded during the trial and do not establish causation. The registry record does not provide event timing, duration, exposure-adjusted rates, adjudication details or a full account of how events were attributed. Small group counts also limit what can be inferred about uncommon events. The figures are descriptive safety information for this study, not a complete characterization of risk.

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

The posted results show a positive estimated difference in CFQ-R respiratory-domain score for ELX/TEZ/IVA compared with TEZ/IVA through Week 24, with a 95% confidence interval that excludes zero. The score direction means that a higher value corresponds to fewer reported respiratory symptoms and better health-related quality of life. The registry's p-value also indicates that the model-based result is statistically inconsistent with a zero difference under the reported analysis assumptions.

This does not mean that every participant had a better score, that every participant's symptoms changed by the group-average amount, or that the effect applies to people outside the trial population. A group mean can mask differences in individual outcomes. The registry does not report the distribution of individual changes or the proportion of participants who improved by a particular amount.

Statistical significance is not, by itself, a measure of clinical importance. No clinically important difference threshold is reported for this endpoint in the registry record. The result therefore supports describing the size and precision of the estimated group contrast, but not categorizing that size as definitively meaningful to participants based only on this information.

The comparison is between two active combination regimens, after a shared run-in, in participants with the stated genotype and over a 24-week treatment period. It does not answer questions about comparisons with no active treatment, other patient groups, other treatment schedules or longer-term outcomes. Secondary measures add context, but their multiplicity handling is not reported and should not be used to overstate the primary finding.

The safety counts are also descriptive and do not establish that a regimen caused or prevented a particular event. Missing-data handling, full analysis details and original sample-size justification are not reported. These limits do not erase the posted estimates; they define what conclusions can reasonably be drawn from this registry record.

18. Why This Trial Matters Statistically

This trial illustrates why an outcome's scale and direction should be understood before interpreting a treatment contrast. The CFQ-R respiratory score is participant-reported, ranges from 0 to 100 and is oriented so that higher scores indicate fewer symptoms and better health-related quality of life. With that context, the positive mean difference can be interpreted without confusing a score increase with worsening symptoms.

It also illustrates the distinction between a model-based analysis and a simple calculation from group summaries. The primary sponsor analysis uses a repeated-measures model, while the recalculation is an unadjusted aggregate comparison. Their estimates are numerically close, but they do not answer exactly the same methodological question. The registry's stated model result remains the main inferential analysis.

Precision, statistical evidence and importance are separate issues. A confidence interval quantifies uncertainty under a model; a p-value addresses compatibility with a null hypothesis; neither alone determines whether a difference matters to participants. The registry does not give a clinically important threshold, so statistical interpretation should not be stretched into a claim about importance.

Finally, the record shows how secondary endpoints and safety counts can broaden a statistical description while also introducing interpretive limits. Multiplicity adjustment, missing-data procedures and several analysis details are not reported. Clear reporting of these elements is essential for evaluating how robust results are and how far they can be generalized. The trial is thus useful not only as a numerical comparison but also as an example of why estimates should be read alongside their design, outcome definitions and reporting gaps.

19. 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 what the registry record reports. The primary comparison is limited to participants with cystic fibrosis who were homozygous for F508del and met the full analysis set definition. The record does not establish how well that population represents people with other genotypes or clinical characteristics. The treatment-period comparison lasted 24 weeks after a 4-week run-in, so the posted result addresses that period rather than longer-term outcomes.

The study compared two active combination regimens. It therefore does not provide a contrast against no treatment or an untreated control. The registry lists 176 enrolled participants, while the primary outcome groups contain 88 and 87 participants; the record does not explain the difference. Participant disposition and endpoint-specific missingness are not reported in enough detail to evaluate that difference.

The primary analysis method is named, but its full model specification is not reported. The registry does not report missing-data procedures, sensitivity analyses, multiplicity handling, interim analyses or the original sample-size justification. The clinically important difference threshold for the primary score is also not reported. These omissions limit independent assessment of robustness, confirmatory status and clinical importance.

The safety summaries are counts and listed terms; event timing, exposure-adjusted rates and attribution details are not reported. The registry also does not provide individual participant outcome distributions. As a result, the group estimates cannot describe variation in individual response or fully characterize uncommon safety outcomes. These are limitations of interpretation from the registry record, not evidence that any unreported analysis or procedure was or was not performed.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del — NCT04105972.
• 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.

23. Record Summary

This completed Phase 3b randomized, double-blind, controlled, parallel-group study enrolled 176 participants with cystic fibrosis who were homozygous for F508del. After a 4-week TEZ/IVA run-in, participants received either TEZ/IVA or ELX/TEZ/IVA during a 24-week treatment period.

The primary endpoint was change in CFQ-R respiratory-domain score from baseline through Week 24. The sponsor-reported model estimated a least-squares mean difference of 15.9 units for ELX/TEZ/IVA compared with TEZ/IVA, with a 95% confidence interval from 11.7 to 20.1 and p < 0.001. Higher scores indicate fewer symptoms and better health-related quality of life.

The registry also reports secondary lung-function and sweat-chloride outcomes and adverse-event counts. Multiplicity procedures, missing-data methods, full model specifications and the original sample-size justification are not reported in the registry record. Interpretation should remain specific to the stated population, comparison and follow-up period.