Personalized Theratyping Trial

Study Overview
=================
Brief Summary
-----------------
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.

Detailed 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.

Official Title
-----------------
Personalized Theratyping Trial

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: Symdeko


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symdeko<br>Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Symdeko, depending on the in vitro response pattern | Drug: Symdeko<br>* 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.<br>* Other names: Ivacaftor;|
| Experimental: Ivacaftor<br>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. | Drug: Symdeko<br>* 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.<br>* Other names: Ivacaftor;|
| Experimental: Orkambi<br>Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Orkambi, depending on the in vitro response pattern | Drug: Symdeko<br>* 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.<br>* Other names: Ivacaftor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| spirometry | change in lung function as measured via spirometry | 32 weeks |