Lumacaftor/ivacaftor in people with cystic fibrosis with an A455E-CFTR mutation.
Adolescent
Adult
Aminophenols
/ therapeutic use
Aminopyridines
/ therapeutic use
Benzodioxoles
/ therapeutic use
Cross-Over Studies
Cystic Fibrosis
/ drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator
/ genetics
Double-Blind Method
Drug Combinations
Female
Humans
Male
Middle Aged
Mutation
Quinolones
/ therapeutic use
Young Adult
A455E–CFTR
Crossover study
Cystic fibrosis
Lumacaftor/ivacaftor
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
21
08
2020
revised:
02
11
2020
accepted:
06
11
2020
pubmed:
30
11
2020
medline:
8
2
2022
entrez:
29
11
2020
Statut:
ppublish
Résumé
Previous in vitro organoid data showed A455E-CFTR, a rare CFTR mutation with 4.1% prevalence in the Netherlands, responds to lumacaftor/ivacaftor (LUM/IVA). We explored LUM/IVA's clinical efficacy in people with CF and ≥1 A455E-CFTR mutation. Participants aged ≥12 years were randomized to 1 of 2 treatment sequences (LUM/IVA→placebo or placebo→LUM/IVA) with an 8-week washout period between. Primary endpoint was absolute change in ppFEV Twenty participants were randomized at 2 sites in the Netherlands. Mean absolute change in ppFEV In this exploratory study, LUM/IVA elicited an in vitro response in organoid swelling and in vivo response in SwCl in participants with CF and ≥1 A455E-CFTR mutation. The primary endpoint (ppFEV
Sections du résumé
BACKGROUND
Previous in vitro organoid data showed A455E-CFTR, a rare CFTR mutation with 4.1% prevalence in the Netherlands, responds to lumacaftor/ivacaftor (LUM/IVA). We explored LUM/IVA's clinical efficacy in people with CF and ≥1 A455E-CFTR mutation.
METHODS
Participants aged ≥12 years were randomized to 1 of 2 treatment sequences (LUM/IVA→placebo or placebo→LUM/IVA) with an 8-week washout period between. Primary endpoint was absolute change in ppFEV
RESULTS
Twenty participants were randomized at 2 sites in the Netherlands. Mean absolute change in ppFEV
CONCLUSIONS
In this exploratory study, LUM/IVA elicited an in vitro response in organoid swelling and in vivo response in SwCl in participants with CF and ≥1 A455E-CFTR mutation. The primary endpoint (ppFEV
Identifiants
pubmed: 33249003
pii: S1569-1993(20)30910-3
doi: 10.1016/j.jcf.2020.11.007
pii:
doi:
Substances chimiques
Aminophenols
0
Aminopyridines
0
Benzodioxoles
0
CFTR protein, human
0
Drug Combinations
0
Quinolones
0
lumacaftor, ivacaftor drug combination
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Banques de données
ClinicalTrials.gov
['NCT03061331']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
761-767Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: JRD, ZY, and NK are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in Vertex Pharmaceuticals Incorporated; PA was employed by Vertex Pharmaceuticals Incorporated at the time the study was conducted; HH reports personal fees from Gilead, PTC, Teva, and Vertex Pharmaceuticals Incorporated, and clinical trials with AbbVie and Vertex Pharmaceuticals Incorporated; JMB reports grants from Eloxx and Proteostasis, travel support from Proteostasis and Vertex Pharmaceuticals Incorporated, and royalties from the Royal Netherlands Academy of Sciences and Arts; RGJV is the CEO of Hubrecht Organoid Technology, a company based on the commercial implementation of the organoid technology, and reports grants and advisory board membership from Vertex Pharmaceuticals Incorporated; CKvdE reports grants from Eloxx, Galapagos NV, Gilead, GSK, Nutricia, ProQR, Proteostasis, Teva, and Vertex Pharmaceuticals Incorporated, and a patent (10006904) with royalties paid. SFB does not have any other disclosures to report.