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Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation: A Phase 3B, Randomized, Placebo-Controlled Study.

  • Year: 2022
  • Date:
  • Author: Mall MA
Source

Am J Respir Crit Care Med. 2022 Jul 11. doi: 10.1164/rccm.202202-0392OC.

Study design (if review, criteria of inclusion for studies)

Randomized controlled trial

Participants

60 CF Children 6 through 11 years of age with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes)

Interventions

Children were randomized to receive either ELX/TEZ/IVA (N = 60) or placebo (N = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ≥30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose).

Outcome measures

The primary endpoint was absolute change in lung clearance index2.5 (LCI2.5) from baseline through Week 24.

Main results

Children given ELX/TEZ/IVA had a mean decrease in LCI2.5 of 2.29 units (95% CI, 1.97 to 2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81, P<0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1), and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95%, CI 6.9 to 15.1) and Cystic Fibrosis Questionnaire-Revised respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0 to 10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity.

Authors' conclusions

In this first randomized, controlled study of a CFTR modulator conducted in children 6 through 11 years of age with F/MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and CFTR function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.

Keywords: CFTR Modulators; Genetic Predisposition to Disease; pharmacological_intervention; placebo; VX-770; VX-661; ivacaftor; Aminophenols; tezacaftor; VX-445; elexacaftor; Trikafta;