VX18-445-110 VX-445/TEZ/IVA Open-label in CF (F/G and F/RF)

  • Research type

    Research Study

  • Full title

    A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

  • IRAS ID

    268821

  • Contact name

    Peter Barry

  • Contact email

    Peter.Barry@MFT.NHS.UK

  • Eudract number

    2019-000833-37

  • Duration of Study in the UK

    2 years, 8 months, 29 days

  • Research summary

    Cystic fibrosis (CF) is a lifelong disease resulting from changes (mutations) in the code for one gene called the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Changes in this gene can affect the amount of the protein made from this gene or how well the protein works. When there is not enough protein or it does not work properly, some fluids in the body become sticky and causes problems in the lungs and other organs. VX-445, tezacaftor and ivacaftor are a triple combination of therapies targeted at improving the function of this protein. Early studies have suggested that this triple combination may improve health in some patients with CF. This clinical trial will evaluate how well the triple combination may treat CF in men and women with CF who are 12 years or older, and who have certain mutations in their CF genes. This study will test the triple combination in people with one copy of a CF gene with a mutation termed F508del and the other copy of a CF gene with a mutation termed a gating or residual function.
    The study will include participants from study VX18-445-104 and all participants will receive active treatment (triple combination of VX-445, tezacaftor and ivacaftor). The study duration is 100 weeks, which includes up to 96 weeks of treatment and a follow-up visit after 4 weeks. The study will check if the triple combination can improve lung function and other measures of health in people with cystic fibrosis.

    Lay summary of study results: Lay Summary Results for VX18-445-110, A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes) This study involved cystic fibrosis (CF) participants who were 12 years old or older. It took place at 84 locations in 12 countries: Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, the Netherlands, Spain, the UK and the USA. 251 people took part in the study.
    The study had 2 parts. In Part A participants got 200 milligrams of Elexacaftor (ELX) once a day, 100 milligrams of Tezacaftor (TEZ) once a day and 150 milligrams of Ivacaftor (IVA) twice a day for 96 weeks. Only patients from certain countries participated in Part B and they got 200 milligrams of ELX once a day, 100 milligrams of TEZ once a day and 150 milligrams of IVA twice a day for 48 weeks. Out of the 251 patients who started, 215 patients completed the study.
    Some people had side effects from the study medication. Common side effects were nausea, diarrhea, feeling tired, headache, fever, worsening of lung symptoms like coughing or shortness of breath, runny nose and sore throat.
    The purpose of this study was to look at CFTR corrector drugs (with or without other medications called potentiators) and how they affect important health benefits and risks in people with cystic fibrosis who have Class II CFTR mutations, like the common F508del mutation. For more information, detailed results are publicly available at https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Cwestminster.rec%40hra.nhs.uk%7C977fe8fb5b174bbd6ed708ddca8b4840%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638889421782789399%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=T4Vsb2Ko5y4sbryjP3vFKY1aabfik6yoLzKYNaGKoNQ%3D&reserved=0, search NCT04058366 or VX18-445-110.

  • REC name

    London - Westminster Research Ethics Committee

  • REC reference

    19/LO/1317

  • Date of REC Opinion

    29 Oct 2019

  • REC opinion

    Further Information Favourable Opinion