Table 3.
Subgroup Analysis of Efficacy Results According to Comparator Cohort.*
| Variable | Phe508del–Gating Genotypes | Phe508del–Residual Function Genotypes | ||
|---|---|---|---|---|
| Elexacaftor–Tezacaftor–Ivacaftor (N = 50) | Active Control: Ivacaftor (N = 45) | Elexacaftor–Tezacaftor–Ivacaftor (N = 82) | Active Control: Tezacaftor–Ivacaftor (N = 81) | |
| Percentage of predicted FEV1 | ||||
| Value at baseline | 66.0±14.8 | 68.1±16.6 | 67.8±16.3 | 68.1±16.4 |
| Absolute change from baseline through wk 8 (95% CI) | 5.8 (4.2 to 7.4) | 0.1 (−1.6 to 1.7) | 2.5 (1.4 to 3.5) | 0.5 (−0.5 to 1.5) |
| Between-group difference (95% CI) | 5.8 (3.5 to 8.0) | 2.0 (0.5 to 3.4) | ||
| Sweat chloride concentration — mmol/liter | ||||
| Value at baseline | 50.9±23.3 | 47.6±19.1 | 64.7±27.9 | 61.4±27.3 |
| Absolute change from baseline through wk 8 (95% CI) | −21.8 (−25.7 to −17.8) | −1.8 (−5.7 to 2.2) | −23.1 (−25.6 to −20.6) | 1.7 (−0.9 to 4.3) |
| Between-group difference (95% CI) | −20.0 (−25.4 to −14.6) | −24.8 (−28.4 to −21.2) | ||
| CFQ-R respiratory domain score† | ||||
| Value at baseline | 76.3±16.4 | 75.8±17.6 | 76.7±16.9 | 78.1±14.7 |
| Absolute change from baseline through wk 8 (95% CI) | 10.2 (6.6 to 13.8) | 1.3 (−2.5 to 5.2) | 10.4 (7.2 to 13.7) | 1.9 (−1.4 to 5.1) |
| Between-group difference (95% CI) | 8.9 (3.8 to 14.0) | 8.5 (4.0 to 13.1) | ||
Plus–minus values are means ±SD. Baseline was defined as the most recent nonmissing measurement before the first dose of trial drug in the treatment period. Absolute changes from baseline are least-squares means. A similar mixed-effects model for repeated measures as for the primary analysis was applied to each subgroup category, with treatment group, visit, and treatment-group–by–visit interaction as fixed effects and continuous baseline percentage of predicted FEV1 and continuous baseline sweat chloride concentration as covariates. Model-based estimates for a given category are shown here provided that the analysis converged in that category. All subgroup analyses, except those involving the primary end point of the absolute change in the percentage of predicted FEV1 from baseline through week 8 with elexacaftor–tezacaftor–ivacaftor, were post hoc.
The minimal clinically important difference for the CFQ-R respiratory domain score is 4 points.