Barry et al.2323 Barry PJ, Mall MA, Álvarez A, Colombo C, de Winter-de Groot KM, Fajac I, et al. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021;385(9):815-825. https://doi.org/10.1056/NEJMoa2100665
https://doi.org/10.1056/NEJMoa2100665...
(NCT04058353)
North America, Europe, and Australia |
Phase 3 double-blind RCT with active control arm |
≥ 12-year-olds with CF and F508del-gating or F508del-residual function genotypes |
ETI
E: 200 mg once daily;
I: 150 mg every 12 h;
T: 100 mg once daily
(N = 132) |
TI or I
I: 150 mg every 12 h; T: 100 mg once daily
(N = 126) |
FEV1%, sweat chloride concentration, score on CFQ respiratory domain, adverse events |
8 weeks |
Heijerman et al.1414 Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial [published correction appears in Lancet. 2020 May 30;395(10238):1694]. Lancet. 2019;394(10212):1940-1948. https://doi.org/10.1016/S0140-6736(19)32597-8
https://doi.org/10.1016/S0140-6736(19)32...
(NCT03525548)
Belgium, Netherlands, UK, and USA
(NCT03525574-extension) |
Phase 3 double-blind RCT with active control arm
Open label extension |
≥ 12-year-olds with CF and homozygous for F508del mutation, FEV₁ 40-90%, stable CF |
ETI
E: 200 mg once daily;
I: 150 mg every 12 h;
T: 100 mg once daily
(N = 55) |
TI
T: 100 mg once daily; I: 150 mg, every 12 h
(N = 52) |
FEV1%, sweat chloride concentration, score on CFQ respiratory domain, adverse events |
4 weeks
96-week extension |
Keating et al.1212 Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, et al. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018;379(17):1612-1620. https://doi.org/10.1056/NEJMoa1807120
https://doi.org/10.1056/NEJMoa1807120...
(NCT03227471)
USA, Netherlands, Belgium, and Australia |
Phase 2 double-blind RCT with active control arm or placebo |
≥ 18-year-olds with CF
F508del-MF genotype patients were randomized to receive triple therapy or a triple placebo control
Patients homozygous for the F508del mutation genotype were randomized to receive triple therapy or active control arm |
F508del-MF genotype:
ETI
E: 50,100, or 200 mg once daily);
I: 150 mg every 12 h;
T: 100 mg once daily
(n = 53)
or
VX-445 in triple combination with T and VX-561
(n = 22)
Homozygous for F508del:
ETI
E: 200 mg/day p.o.;
T: 100 mg/day; I: 150 mg every 12 h
(n = 21)
[64 patients received E 200 mg per day p.o.]
(N = 96) |
F508del-MF genotype:
placebo
(n = 12)
or
VX-445 in triple combination
(n = 8)
Homozygous for F508del:
TI
I: 150 mg every 12 h;
T: 100 mg once daily
(n = 7)
(N = 27) |
FEV1%, score on CFQ respiratory domain, adverse events |
4 weeks |
Mall et al.1616 Mall MA, Brugha R, Gartner S, Legg J, Moeller A, Mondejar-Lopez P, et al. 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. Am J Respir Crit Care Med. 2022;206(11):1361-1369. https://doi.org/10.1164/rccm.202202-0392OC
https://doi.org/10.1164/rccm.202202-0392...
(NCT04353817)
Australia, Canada, Denmark, France, Germany, Israel, Netherlands, Spain, Switzerland, and UK |
Phase 3 double-blind placebo-controlled RCT |
6-12-year-olds with CF and F508del-MF genotypes, FEV₁ 40-90%, stable CF |
Children < 30 kg:
E: 100 mg once daily;
T: 50 mg once daily;
I: 75 every 12 h
Children ≥ 30 kg:
E: 200 mg once daily;
T: 100 mg once daily;
I: 150 every 12 h
(N = 60) |
Placebo
(N = 61) |
FEV1%, lung clearance index, sweat chloride concentration, score on CFQ respiratory domain, adverse events |
24 weeks |
Middleton et al.1313 Middleton PG, Mall MA, Drevínek P, Lands LC, McKone EF, Polineni D, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809-1819. https://doi.org/10.1056/NEJMoa1908639
https://doi.org/10.1056/NEJMoa1908639...
(NCT03525444)
USA, Europe, and Australia
Extension
(NCT03525574) |
Phase 3 double-blind placebo-controlled RCT
Open label-extension |
≥ 12-year-olds with CF and heterozygous for the F508del-MF genotype, FEV₁ 40-90%, stable CF |
ETI
E: 200 mg once daily; I: 150 mg every 12 h;
T: 100 mg once daily
(N = 201) |
Placebo
(N = 204) |
FEV1%, exacerbations, BMI, sweat chloride concentration, score on CFQ respiratory domain, adverse events |
24 weeks
96-week extension |
Sutharsan et al.1515 Sutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, et al. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022;10(3):267-277. https://doi.org/10.1016/S2213-2600(21)00454-9
https://doi.org/10.1016/S2213-2600(21)00...
(NCT04105972)
Australia, Belgium, Germany, and UK |
Phase 3 double-blind RCT with active control arm |
≥ 12-year-olds with CF and homozygous for F508del, FEV₁ 40-90%, stable CF |
ETI
E: 200 mg once daily; I: 150 mg every 12 h; T: 100 mg once daily
(N = 87) |
TI
I: 150 mg every 12 h;
T: 100 mg once daily
(N = 88) |
FEV1%, sweat chloride concentration, score on CFQ respiratory domain, adverse events |
24 weeks |
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