Overview
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.
Description
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.
Eligibility
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