Trikafta in Cystic Fibrosis Patients

Summary

Participation Requirements

Description

Cystic Fibrosis (CF) is a life threatening genetic disorder resulting from mutations found in the gene known as the cystic fibrosis transmembrane conductance regulator (CFTR). Defects in this gene prevent correct chloride transport in and out of cells. It has become increasingly important to develop...

Cystic Fibrosis (CF) is a life threatening genetic disorder resulting from mutations found in the gene known as the cystic fibrosis transmembrane conductance regulator (CFTR). Defects in this gene prevent correct chloride transport in and out of cells. It has become increasingly important to develop new in vitro model systems capable of predicting in vivo clinical effectiveness of modulator therapy among patients with CF. This objective represents a significant and unmet need for advancing personalized therapeutics in the disease. The current trial is intended to show for the first time that primary iPS cells differentiated to an airway epithelial phenotype can be used to predict in vivo clinical response for rare CF patient populations - with the long-term goal of facilitating drug access for individuals with unusual (or even private) CF variants. Trikafta is currently approved for patients with CF carrying at least one copy of the common F508del variant. This study is a clinical study of 22 subjects without the F508del mutation, carrying partial function mutations not approved for Trikafta, and who are not expected to be approved for CFTR modulator treatment in the immediate future. Each participant will have clinical and/or preclinical evidence that Trikafta should offer benefit, and each will be given Trikafta for approximately four weeks. The researchers will monitor clinical endpoints that include FEV1, sweat chloride, and nasal potential difference. The study will differentiate iPS cells from each subject to generate airway epithelial monolayers that can be tested for response to Trikafta. In this way, this study will evaluate an emerging and readily accessible in vitro surrogate endpoint as a predictor of clinical response. This trial will also serve as a pilot/test case for other clinical protocols relevant to patients with rare CFTR variants and evidence of residual function who do not have an approved modulator therapy-due to rarity of their mutation. It is hypothesized that a robust correlation will be established between in vitro Trikafta responsiveness of iPS cells and in vivo benefit (FEV1) in patients, and provide a powerful tool for utilizing iPS cells to identify rare CF patient populations most suitable for cystic fibrosis modulator therapy.

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