Table 2.
Primary and Key Secondary Efficacy End Points.*
| End Point | Elexacaftor–Tezacaftor–Ivacaftor (N = 200) |
Placebo (N = 203) |
Difference (95% CI)† | P Value |
|---|---|---|---|---|
| Primary end point: absolute change in percentage of predicted FEV1 from baseline at wk 4 (95% CI)‡ | 13.6 (12.4 to 14.8) | −0.2 (−1.3 to 1.0) | 13.8 (12.1 to 15.4) | <0.001 |
| Key secondary end points | ||||
| Absolute change in percentage of predicted FEV1 from baseline through wk 24 (95% CI) | 13.9 (12.8 to 15.0) | −0.4 (−1.5 to 0.7) | 14.3 (12.7 to 15.8) | <0.001 |
| Pulmonary exacerbations through wk 24 — no. of events (annualized estimated event rate)§ | 41 (0.37) | 113 (0.98) | 0.37 (0.25 to 0.55) | <0.001 |
| Absolute change in sweat chloride concentration from baseline through wk 24 (95% CI) — mmol/liter |
−42.2 (−44.0 to −40.4) | −0.4 (−2.2 to 1.4) | −41.8 (−44.4 to −39.3) | <0.001 |
| Absolute change in CFQ-R respiratory domain score from baseline through wk 24 (95% CI)¶ | 17.5 (15.6 to 19.5) | −2.7 (−4.6 to −0.8) | 20.2 (17.5 to 23.0) | <0.001 |
| Absolute change in body-mass index from baseline at wk 24 (95% CI) | 1.13 (0.99 to 1.26) | 0.09 (−0.05 to 0.22) | 1.04 (0.85 to 1.23) | <0.001 |
| Absolute change in sweat chloride concentration from baseline at wk 4 (95% CI) — mmol/liter | −41.2 (−43.1 to −39.2) | 0.1 (−1.9 to 2.0) | −41.2 (−44.0 to −38.5) | <0.001 |
| Absolute change in CFQ-R respiratory domain score from baseline at wk 4 (95% CI)¶ | 18.1 (15.9 to 20.4) | −1.9 (−4.2 to 0.3) | 20.1 (16.9 to 23.2) | <0.001 |
Data are least-squares means with 95% confidence intervals (CIs), except for pulmonary exacerbations through week 24, for which the number of events and the annualized estimated event rate are shown.
The difference is the least-squares mean difference between the elexacaftor–tezacaftor–ivacaftor group and the placebo group based on a mixed-effects model for repeated measures, except for the number of pulmonary exacerbations, for which the rate ratio is shown.
The primary end point was assessed at the prespecified interim analysis at week 4, which included all patients who underwent randomization and received at least one dose of elexacaftor–tezacaftor–ivacaftor or placebo.
The analysis was based on a negative binomial-regression model (48 weeks per year was used to calculate the event rate).
For the CFQ-R respiratory domain score (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms), the minimum clinically important difference is 4 points.