Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations.
J Cyst Fibros
; 19(6): 962-968, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32546431
ABSTRACT
BACKGROUND:
Tezacaftor/ivacaftor is a CFTR modulator approved to treat people with cystic fibrosis (pwCF) who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function mutation (F/RF). This randomized, double-blind, placebo-controlled Phase 3 study evaluated the efficacy, safety, tolerability, and pharmacokinetics (PK) of tezacaftor/ivacaftor in participants ≥12 years of age heterozygous for the F508del-CFTR mutation and a minimal function mutation (F/MF), which produces no CFTR protein or a protein unresponsive to tezacaftor/ivacaftor in vitro.METHODS:
Participants were randomized 11 to receive tezacaftor/ivacaftor or placebo for 12 weeks. The primary endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) between the tezacaftor/ivacaftor and placebo groups through week 12. Key secondary endpoints included absolute change from baseline in CF Questionnaire-Revised respiratory domain scores and the number of pulmonary exacerbations through week 12 and the absolute change from baseline in body mass index at week 12. A prespecified interim analysis (IA) for futility was conducted when approximately 50% of a planned enrollment of 300 participants reached week 12 of the study.RESULTS:
At the time of the IA, 83 participants were randomized to tezacaftor/ivacaftor and 85 to placebo; 165 participants completed treatment. The study failed to demonstrate that tezacaftor/ivacaftor significantly improved ppFEV1 or any of the key secondary endpoints and was terminated for futility. The safety profile and PK parameters of tezacaftor/ivacaftor were similar to those reported in prior studies in participants ≥12 years of age with CF.CONCLUSIONS:
Tezacaftor/ivacaftor did not show a clinically meaningful benefit in participants with F/MF genotypes but was generally safe and well tolerated, consistent with the safety profile reported in other Phase 3 studies (NCT02516410).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolonas
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Regulador de Condutância Transmembrana em Fibrose Cística
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Fibrose Cística
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Benzodioxóis
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Agonistas dos Canais de Cloreto
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Aminofenóis
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Indóis
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Cyst Fibros
Ano de publicação:
2020
Tipo de documento:
Article