A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

Summary

This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Timeline

Start

2018-06-15

Primary completion

2019-04-24

Completion

2019-04-24

Outcome

Met primary endpoint

registry Placebo vs VX-445/TEZ/IVA TC; p <0.0001; Least Squares (LS) Mean Difference 13.8 (95% CI 12.1 to 15.4) NCT03525444 ↗

paper Elexacaftor-tezacaftor-ivacaftor, relative to placebo, resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks PMID 31697873 ↗

Publications

• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
• Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	IVA	Unknown	150 mg	Oral
Subject	elexacaftor	Small molecule	100 mg	Oral
Subject	elexacaftor	Small molecule	150 mg	Oral
Subject	elexacaftor	Small molecule	200 mg	Oral

Indications