None listed
Conditions
Brief summary
This study aims to evaluate whether an in vitro test enables identification of people with Cystic Fibrosis rare mutations who are clinically responsive to CFTR modulators. Cystic Fibrosis patients with two non-F508del mutations with a positive response in the in vitro testing will undergo cycles of treatment with a triple combination -Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) and matched placebo. Short term improvement in lung function (FEV1) and CF-related symptoms will be used to determine if they respond to the treatment.
Interventions
This will be a crossover study whereby participants will switch between a TGA-approved triple combination drug and matched placebo after each washout period.
For a treatment block, participants will take orally a film-coated tablet containing Elexacaftor 150mg, Tezacaftor 50mg and Ivacaftor 75mg in the morning, and a film-coated tablet containing Ivacaftor 150mg in the evening, or a matched placebo, for 14 days, followed by a 14 days washout period. Two treatment blocks constitute a treatment cy
This will be a crossover study whereby participants will switch between a TGA-approved triple combination drug and matched placebo after each washout period. For a treatment block, participants will take orally a film-coated tablet containing Elexacaftor 150mg, Tezacaftor 50mg and Ivacaftor 75mg in the morning, and a film-coated tablet containing Ivacaftor 150mg in the evening, or a matched placebo, for 14 days, followed by a 14 days washout period. Two treatment blocks constitute a treatment cycle. Participants will undergo at least two treatment cycles and up to four treatment cycles during the study, depending on the results of the Bayesian analysis from the first two cycles. Intervention adherence will be assessed by reconciliation of number of tablets dispensed and number of tablets returned.
Sponsors
The University of Newcastle
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with CF who are 6 years old without a F508del mutation, and with a best measured ppFEV1 in the preceding 6 months between 40% and 90%. Participants that have provided or are willing to provide a colonic/rectal biopsy for 3D organoid culture and have a demonstrated positive response to ETI in an in vitro assay.
Exclusion criteria
History of lung transplantation Receiving a CFTR modulator therapy in the 28 days prior to the screening visit Any of the following abnormal laboratory values at screening: Hemoglobin lower than10 g/dL Total bilirubin 2 times upper limit of normal (ULN) Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) 3 times ULN An acute upper or lower respiratory infection, pulmonary exacerbation(s) (PEx), or changes in therapy (including antibiotics) for sinopulmonary disease within 28 days before the first dose of study medication in the Run-in Period (Day -28). An established contraindication the study medication i.e., ETI Pregnant or nursing females. All female subjects must have a negative pregnancy test at Screening (urine test). A life expectancy of less than 12 months
Outcome results
None listed