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). This
clinical study will enroll 22 participants 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 be given Trikafta for
approximately four weeks. The study researchers will monitor clinical endpoints that include
forced expiratory volume (FEV1), sweat chloride, and nasal potential difference.
Additionally, the researchers will obtain skin biopsy material from each subject so that
induced pluripotent stem (iPS) cells can be modified into airway cell monolayers and tested
for response to Trikafta. In this way, the study will evaluate an emerging and readily
accessible in vitro endpoint as a predictor of clinical response. This study will serve as a
pilot/test case for other clinical protocols relevant to patients with rare CFTR variants who
do not currently receive modulator therapies. It is hypothesized that a robust correlation
will be established between in vitro Trikafta responsiveness of iPS cells and in vivo benefit
(FEV1) to patients, and will provide a new tool for utilizing iPS to identify patient
populations most suitable for cystic fibrosis modulator therapy.