A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F) (NCT03525548), a randomized phase 3 study. The primary outcome is Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1).

2. Clinical Question

The question is specific to this population, these regimens, and the short treatment period recorded. It is not a comparison with no active treatment: both groups had a tezacaftor/ivacaftor run-in, and the control group continued that regimen during the treatment period. The primary outcome is a lung-function measure, while the registry also lists changes in sweat chloride and the respiratory domain of the Cystic Fibrosis Questionnaire-Revised, as well as safety and drug-concentration outcomes.

The registry record describes a randomized, double-blind, controlled study. Those design features support a comparison between assigned groups, but they do not by themselves establish the details of every analysis decision. The record does not report the original sample-size justification or the full statistical analysis plan.

3. Trial Design

This was a Phase 3, randomized, double-blind, controlled, parallel-group study. The registry lists quadruple masking. It records enrollment of 113 and a completed status. The study start date was 2018-08-03, and primary completion was 2018-12-28. The condition was cystic fibrosis, and the stated target population was people homozygous for the F508del mutation.

The comparison was between VX-445/tezacaftor/ivacaftor triple combination therapy and tezacaftor/ivacaftor. Participants in both groups had a 4-week run-in with tezacaftor/ivacaftor before the 4-week treatment period. In the triple-combination group, the morning fixed-dose combination contained VX-445 200 mg, tezacaftor 100 mg, and ivacaftor 150 mg, with a separate ivacaftor 150 mg evening dose. In the comparator group, the morning fixed-dose combination contained tezacaftor 100 mg and ivacaftor 150 mg, also with a separate ivacaftor 150 mg evening dose.

For the primary outcome, the posted group summaries include 52 participants in the tezacaftor/ivacaftor group and 55 in the triple-combination group. The primary analysis population was the full analysis set, defined in the record as randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug during the triple-combination treatment period. That definition is narrower than simply describing everyone enrolled, and it is the population named for interpreting the reported primary outcome.

The registry does not report the protocol’s original design assumptions, including the target effect used for planning, the sample-size justification, or planned interim analyses. Details about allocation concealment and the precise implementation of masking are also not reported in the registry record. The registry lists other interventions, including ivacaftor and placebo, but the arm descriptions relevant to the posted primary comparison concern the two active regimens.

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 participants with cystic fibrosis (CF) aged 12 years or older.

Overall Study

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 gene (CFTR) allele mutation and received at least 1 dose of study drug in the TC 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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1), measured over From Baseline at Week 4.

The primary endpoint was absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline at Week 4. FEV1 is the volume of air a person can forcibly exhale in one second after a full inspiration. Percent predicted expresses that measurement relative to a predicted value; the posted outcome is expressed in percentage points.

FEV1 is used in cystic fibrosis trials as a measure of lung function. A change from baseline focuses the comparison on how the measure shifted during the study period, rather than on the Week 4 value alone. The registry reports least-squares mean changes for each group and a least-squares mean difference between groups. Least-squares means are model-based group estimates; they are not necessarily the same as simple arithmetic averages.

The reported comparison is for change from baseline at Week 4, following a 4-week treatment period. The registry defines the primary analysis population as the full analysis set, including randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug in the triple-combination treatment period. The endpoint therefore answers a short-term lung-function question for the named analysis population. It does not, by itself, describe longer-term outcomes, other aspects of cystic fibrosis, or the overall balance of benefits and harms.

7. Results Posted in the Registry

• VX-445/TEZ/IVA TC: mean 10.40 versus 0.40 on control; difference 10.00 (95% CI 7.51 to 12.49), standardized effect d = 1.52; 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 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:
  • VX-445/TEZ/IVA TC: mean -43.40 versus 1.70 on control; difference -45.10 (95% CI -49.95 to -40.25), standardized effect d = -3.53; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for VX-445/TEZ/IVA TC than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain 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 errors.
• Result:
  • VX-445/TEZ/IVA TC: mean 16.00 versus -1.40 on control; difference 17.40 (95% CI 11.86 to 22.94), standardized effect d = 1.19; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for VX-445/TEZ/IVA TC than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary comparative results follow a consistent overall pattern across the two measured continuous outcomes: the triple-combination group’s change differs from the tezacaftor/ivacaftor group’s change in the direction reported by the sponsor’s analyses. These outcomes concern sweat chloride and the respiratory domain of the Cystic Fibrosis Questionnaire-Revised. They provide context alongside the primary lung-function result, but they measure different aspects of the trial and should not be treated as substitutes for the primary endpoint.

The registry reports model-based comparisons for these outcomes, with 95% confidence intervals and p-values. Those estimates are consistent with the direction of the primary result, but each endpoint has its own measurement scale and interpretation. A pattern across outcomes may be informative, while the analyses still need to be considered in light of their definitions, measurement time, and uncertainty.

Unadjusted secondary results carry less confirmatory weight when several outcomes are tested and no multiplicity strategy is reported. If many hypotheses are examined, the chance of observing nominally notable results can increase. This is a general statistical issue, not evidence that any particular posted result is invalid. The registry record does not report whether secondary tests were adjusted, ranked, or designated as confirmatory versus exploratory.

The record also lists safety and tolerability and observed pre-dose concentrations among the secondary outcomes. Detailed comparative estimates for those outcomes are not presented in the posted continuous-outcome results, so their overall pattern cannot be inferred from the two continuous secondary endpoints.

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

• Absolute Change in Sweat Chloride (SwCl)
• Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
• Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
• Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA

9. Statistical Interpretation

10. Statistical Methods Explained

The primary result is reported as a least-squares mean difference from a mixed-effects model for repeated measures. This is a model-based comparison of the groups’ changes over the recorded measurement period. The registry gives the estimate, a 95% confidence interval, and a p-value, but the detailed model specification and full analysis plan are not reported in the registry record.

What does a least-squares mean represent?

In general, a least-squares mean is an estimate produced by a statistical model. Depending on the model, it may account for specified factors or repeated measurements rather than simply averaging the observed values within each group. The registry names the method as a mixed-effects model for repeated measures, but does not list the covariates, covariance structure, handling of baseline values, or other implementation details. Those choices therefore cannot be reconstructed from the posted summary.

The primary group estimates are 0.4 and 10.4 percentage points, and the sponsor reports their least-squares mean difference as 10 percentage points. The unadjusted recalculation is 10.0, based on the posted group summaries. Such a recalculation is a simple comparison of the available summary statistics, not a replacement for the sponsor’s repeated-measures model. It does not reproduce any model adjustments or account for details that are absent from the summaries.

How should the p-value be read?

In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The sponsor reports p < 0.001 for the primary comparison; the unadjusted recalculation reports p <0.001. These are separate presentations of the model-based and recalculated analyses, rather than competing estimates of the same analysis procedure.

The sponsor labels the reported primary analysis as a superiority comparison. That label describes the intended statistical direction of the reported test. The estimate and interval convey more about magnitude and uncertainty than a thresholded p-value alone. A small p-value does not resolve whether the size of the change is meaningful to patients or how long it persists.

Why can repeated-measures models be useful?

In general, repeated-measures methods can use outcome measurements collected at multiple times and account for the fact that measurements from the same participant are related. Such methods can also estimate a group contrast at a specified time. Here, the endpoint is defined as change from baseline at Week 4, and the named sponsor method is a mixed-effects model for repeated measure. The registry record does not provide enough detail to determine which observations and time points entered the fitted model, or what assumptions were used for incomplete records.

The posted group spreads for the primary endpoint are standard errors, not standard deviations. A standard error describes the estimated uncertainty of a group estimate; it does not directly describe the variability among individual participants. The recalculated comparison includes an approximate pooled standard deviation, marked as approximate in the underlying analysis. In general, dispersion estimates derived from standard errors and group sizes may not match the trial’s participant-level variability exactly, especially when the reported group estimates come from a model.

What does the recalculation add?

The recalculated results offer a transparent, unadjusted check using the posted summary estimates. They can help readers understand the rough scale and uncertainty of a group contrast, but they are not a second trial analysis based on participant-level observations. The reported recalculated confidence interval for the primary comparison is 7.505 to 12.49, compared with the sponsor’s model-based interval of 7.4 to 12.6. Since the discrepancy flag is false, the registry’s reported analysis and the simple recalculation are broadly aligned; the sponsor’s modeled result remains the primary reported estimate.

General statistical caution applies to all model-based estimates: validity depends on the study design, the quality of measurement, the model specification, and how missing observations are handled. The registry does not report enough information to evaluate each of those elements in detail. The analysis population definition is reported, but information on protocol deviations, analysis exclusions beyond that definition, and sensitivity analyses is not reported in the registry record.

11. Confidence Intervals and Precision

The sponsor’s 95% confidence interval for the primary least-squares mean difference extends from 7.4 to 12.6 percentage points. It describes a range of values compatible with the data under the model and its assumptions. Because the interval excludes zero, it is consistent with the reported superiority test. The interval is not a guarantee that the true effect lies within its limits, nor does it express the range of individual participant responses.

The unadjusted recalculation gives a 95% confidence interval from 7.505 to 12.49 percentage points. Its limits are close to those from the sponsor’s repeated-measures model. Differences in the limits are expected when the methods differ: the sponsor reports a model-based estimate, while the recalculation uses posted summary statistics and is unadjusted. The record does not flag a discrepancy between these analyses.

Precision concerns how narrowly an estimate is determined, whereas clinical importance concerns whether the magnitude matters in practice. A confidence interval can inform the former, but the registry record does not provide a threshold for interpreting the primary endpoint’s clinical importance. Nor does the interval describe how results vary among individuals. The group-level estimate and its interval should therefore be read as uncertainty about the average contrast, not as a forecast for any particular participant.

The reported group standard errors are 0.9 for both arms. They quantify uncertainty in the estimated group means, not participant-to-participant spread. The sponsor’s confidence interval is the relevant interval for the model-based primary analysis; the recalculated interval is best understood as a simple unadjusted check.

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 figures are planning illustrations based on the observed effect, not the original trial design. For continuous outcomes such as these, the listed figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect as the effect to detect. The registry record does not report the trial’s own original sample-size assumptions.

The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column uses a higher chance of detection and therefore generally calls for more participants per arm for the same effect. These are planning quantities, not probabilities that the observed result is correct.

Rows that plan for a smaller fraction of the observed effect require more participants per arm than rows planning for the full observed effect. This reflects a general statistical principle: smaller group differences are harder to distinguish from random variation at a fixed level of precision. The displayed values should not be treated as recommendations for another study without considering its population, endpoint, design, variability, and analysis approach. This is not observed power.

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 = 10.000; pooled standard deviation σ = 6.586.
2. n = 2 × (1.96 + 0.842)² × 6.586² / 10.000² = 6.8, rounded up to 7 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 <- 10                      # observed difference in means
sigma <- 6.58556863799279                     # 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(3525548)
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 = 7 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 13 (80% power), 17 (90% power)
 50% of observed effect: n per arm = 28 (80% power), 37 (90% power)
power.t.test: 7.9 
Simulated power at n = 7 per arm: 0.746 (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 primary analysis is reported as a mixed-effects model for repeated measures, with a least-squares mean difference of 10 percentage points, a 95% confidence interval from 7.4 to 12.6, and p < 0.001. The registry labels it a superiority analysis. This is the trial’s own reported result and should be distinguished from the simple unadjusted recalculation.

The recalculation based on the posted summary statistics estimates a difference of 10.0 percentage points, with a 95% confidence interval from 7.505 to 12.49 and p <0.001. The recalculated value is close to the sponsor’s estimate, and the record does not identify a discrepancy. The slightly different interval limits and p-value presentation reflect the different analysis approaches and reporting precision.

The recalculation is useful as a check on the scale of the posted contrast, but it cannot reproduce the sponsor’s repeated-measures model or its unreported implementation details. It should not displace the sponsor’s own analysis. The registry record does not report the full model specification, the trial’s original sample-size rationale, or whether additional sensitivity analyses were conducted.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, time point, contrast, or hypothesis. In general, each additional test can create another opportunity for a result to appear statistically notable by chance. Whether an adjustment is appropriate depends on the study’s goals and prespecified analysis strategy. The registry lists a primary outcome and multiple secondary outcomes, but the multiplicity strategy is not reported in the registry record.

The primary result is reported with a 95% confidence interval and a p-value from the sponsor’s mixed-effects model for repeated measures. The record does not state whether that primary test was part of a hierarchy, whether secondary outcomes were tested only after a primary result, or whether any family-wise error or false-discovery procedure was used. Accordingly, the secondary p-values should not automatically be interpreted as confirmatory evidence independent of the primary analysis.

The record defines the primary analysis population as the full analysis set: randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug during the triple-combination treatment period. That definition is important for understanding who contributes to the stated primary analysis. The registry does not report how many participants were excluded from that set, the reasons for any exclusions, or how the analysis addressed protocol deviations.

Missing-data handling is also not reported in the registry record. The mixed-effects model name alone does not reveal what happened when a participant missed a visit or had an unavailable measurement. Details about assumptions for missing outcomes, imputation, sensitivity analyses, and robustness checks are not reported. These omissions limit a full assessment of how incomplete data could affect the estimates, but they do not alter the numerical results that the registry reports.

The registry also does not report interim analyses or stopping rules. No conclusion about whether such procedures were planned or performed should be inferred from their absence in the posted 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 (1.9%), rash (1.8%).

The registry reports serious adverse events in 1 participant among 52 at risk in the tezacaftor/ivacaftor group and 2 participants among 55 at risk in the VX-445/tezacaftor/ivacaftor group. Other adverse events were reported for 25 participants among 52 at risk and 24 among 55 at risk, respectively. The registry records no deaths in either group.

These are participant counts within the groups shown in the registry, not estimates of comparative risk adjusted for exposure or other factors. The record lists infective pulmonary exacerbation of cystic fibrosis at 1.9% and rash at 1.8% among the top serious terms, but does not give enough detail in these summaries to assign those terms to a specific arm. The counts describe events recorded during the trial; they do not establish that a regimen caused an event or rule out uncommon harms.

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

The result describes a group-level difference in change in ppFEV1 from baseline to Week 4 between the two regimens in the primary analysis population. The sponsor’s repeated-measures analysis estimates a difference of 10 percentage points, with a 95% confidence interval from 7.4 to 12.6. The reported interval and p-value indicate that the model-based comparison is inconsistent with a zero difference under the analysis assumptions.

That finding does not, by itself, establish how important the difference is to participants. The registry does not provide a clinical-importance threshold for the endpoint, and statistical evidence is not the same as clinical interpretation. A group mean also does not show whether every participant changed in the same way, how many improved or worsened, or how individual responses were distributed.

The result is limited to the population and treatment comparison described: participants with cystic fibrosis homozygous for F508del, after a tezacaftor/ivacaftor run-in, comparing triple combination therapy with continued tezacaftor/ivacaftor. It addresses the Week 4 outcome after a 4-week treatment period. It does not establish what happened over longer follow-up or in other cystic fibrosis populations.

The registry also posts secondary outcome comparisons and safety counts. Those results add context but do not answer the same question as the primary endpoint, and the record does not report a multiplicity strategy for the secondary analyses. Safety counts are descriptive and should not be read as a complete account of all possible harms. The results do not provide medical advice or a basis for individual treatment decisions.

18. Why This Trial Matters Statistically

Statistically, this trial is an example of a randomized active-regimen comparison in which the primary result is presented using both a model-based analysis and a simple recalculation from posted summaries. The sponsor’s repeated-measures model reports the least-squares mean contrast, while the recalculation offers a separate, unadjusted check. Their close estimates illustrate how a summary-statistic check can help readers understand the scale of a reported result without replacing the trial analysis.

The design also clarifies the comparison being estimated. Both groups had a tezacaftor/ivacaftor run-in, and the treatment contrast concerns adding VX-445 during the treatment period. Interpreting results accurately requires attention to this comparator, the F508del homozygous population, and the short Week 4 timeframe, rather than treating the result as a generic comparison with no treatment.

The record highlights the value of reading confidence intervals alongside p-values. The interval conveys the range of estimates compatible with the model and data, while the p-value addresses a hypothesis test. Neither measure alone determines clinical importance. The additional secondary outcomes can provide broader context, but multiplicity and incomplete reporting of analysis details affect how strongly they can support confirmatory conclusions.

Finally, the registry’s limits matter as much as its estimates. The analysis population is defined, but the detailed missing-data approach, complete model specification, original sample-size rationale, and multiplicity plan are not reported. Clear separation of reported results, recalculated checks, and unreported methods is essential to a statistically careful reading.

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.

The registry record gives a limited account of the analysis methods. It names a mixed-effects model for repeated measures but does not report the full model specification, including covariates, covariance assumptions, or the treatment of incomplete measurements. These details matter when assessing model-based estimates and their uncertainty.

The primary endpoint is measured at Week 4 after a 4-week treatment period. The record therefore does not establish durability or longer-term outcomes. The study’s stated population is also specific to cystic fibrosis participants homozygous for F508del; generalization beyond that group is not established by this comparison.

The study includes a run-in with tezacaftor/ivacaftor in both arms, so the result is a comparison of triple combination therapy with continued tezacaftor/ivacaftor after that run-in. It should not be interpreted as a comparison with placebo alone. The registry lists placebo and other interventions, but the arm descriptions for the primary comparison identify the two active regimens.

The record does not report the original sample-size justification, multiplicity plan, interim analyses, or missing-data sensitivity analyses. It also does not provide a clinical-importance threshold for interpreting the primary estimate. The recalculated interval is based on posted summary statistics rather than participant-level data, and the pooled standard deviation used in that recalculation is marked approximate. These limitations constrain independent evaluation, even though the recalculated primary contrast is close to the sponsor’s reported result.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F) — NCT03525548.
• Registry record last updated 2020-01-27; status last verified 2020-01.
• Results first posted 2020-01-27.
• 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

The registry describes a completed, randomized, double-blind, controlled Phase 3 parallel-group study of VX-445/tezacaftor/ivacaftor versus tezacaftor/ivacaftor in cystic fibrosis participants homozygous for F508del. Enrollment was 113. Both groups had a 4-week tezacaftor/ivacaftor run-in followed by a 4-week treatment period.

The primary endpoint was change from baseline to Week 4 in ppFEV1. The sponsor’s mixed-effects model for repeated measures reported a least-squares mean difference of 10 percentage points, with a 95% confidence interval from 7.4 to 12.6 and p < 0.001. The unadjusted recalculation was close to the reported analysis. The registry also reports secondary outcomes and adverse-event counts, while important details about multiplicity, missing-data handling, and the original sample-size rationale are not reported in the registry record.