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