Personalized Theratyping Trial

The purpose of this study is to explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs. Symdeko (Tezacaftor/Ivacaftor), Orkambi (Ivacaftor and Lumacaftor), correctors of CFTR misfolding and Kalydeco (Ivacaftor), a potentiator of abnormal CFTR gating, will be explored as a treatment for patients with other CF mutations than those currently approved. Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Symdeko, or Orkambi, depending on the in vitro response pattern. Patients who have mutation response to a potentiator of CFTR function will be given Ivacaftor monotherapy. Patients with a mutation equivalent to wild type will be given Ivacaftor. If the patient is 6-12 years old, we will only study Orkambi or ivacaftor as symdeko is not yet FDA approved in this patient population.

Inclusion criteria

• Diagnosis of CF
• Age ≥6 y.o.
• CFTR mutation that may respond to approved correctors/potentiators in the opinion of the study investigators
• Informed Consent/Assent
• Stable CF pulmonary regimen

Exclusion criteria

• Exacerbation requiring antibiotic or steroids for >28 days before trial entry
• Ongoing participation in a CFTR modulator study
• Active smoking in the past 6 months
• History of solid organ transplant
• Any condition which precludes the use of CFTR modulators: e.g. advanced cirrhosis, End-stage Renal Disease (ESRD)
• Any condition that precludes the patient from participation in the opinion of the investigator
• Any meds that have significant drug-drug interactions or any other off label use of CFTR modulators