Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)

RETRIAL is a prospective, longitudinal, observational, multi-site study designed to observe what happens when people with Cystic Fibrosis (PWCF) with a history new/worsening mental health symptoms or liver toxicity while taking elexacaftor/tezacaftor/ivacaftor (ETI), start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

RETRIAL is a prospective, longitudinal, observational, multi-site study designed to observe what happens when people with Cystic Fibrosis (PWCF) ages 6 and up start taking vanzacaftor/tezacaftor/deutivacaftor (VTD) and have a history of (1) new or worsening mental health symptoms (MH) while on elexacaftor/tezacaftor/ivacaftor (ETI) requiring discontinuation or change from standard dosing (RETRIAL-MH), OR (2) liver-related intolerance to ETI requiring dose modification or discontinuation (RETRIAL-Liver).

Eligibility Criteria:
Inclusion Criteria:

RETRIAL-MH:

* PWCF age 6 years and up (if age is \< 12 years old, the PWCF's caregiver will complete daily diaries and surveys; see "Caregiver Participant Inclusion Criteria" below)
* Eligible for VTD
* Experienced new or worsening mental health symptoms after initiating ETI, which led to one of the following changes in treatment to currently taking:

  1. No modulators
  2. A modulator other than ETI
  3. A flipped dose of ETI
  4. A reduced dose of ETI
* Willing to delay first VTD triple dose for short period of time to complete the Baseline assessments
* Has access to a smart device (phone, tablet, etc.) capable of receiving text messages
* Is English-speaking.

RETRIAL-LIVER:

* A person with CF age 6 years and up;
* Eligible for VTD;
* Experienced liver toxicity (as defined by local care team) after initiating ETI, which led to one of the following changes in treatment: currently

  1. taking no modulators; or
  2. taking a modulator other than ETI; or
  3. taking a reduced or altered dose of ETI;
* Willing to delay first VTD triple dose for short period of time to complete the Baseline assessments;
* Has access to a smart device (phone, tablet, etc.) capable of receiving text messages;
* Is English-speaking.

Exclusion Criteria:

RETRIAL-MH:

* Cannot access VTD
* Unable or unwilling to follow protocol
* Having a person in the same household who is also enrolled in the study (only for \<18 years)
* Is actively listed on any transplant list, or is less than 3 months post-transplant surgery
* Is currently pregnant (test not required)
* Any situation, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

RETRIAL-LIVER:

* Cannot access VTD;
* Unable or unwilling to follow protocol;
* Having a person in the same household who is also enrolled in the study (only for \<18 years);
* Any person with other known liver disease (non-CF related);
* Is actively listed on any transplant list or had a liver transplant;
* Is currently pregnant (test not required);
* Any situation, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

RETRIAL-MH Caregiver Participant:

Inclusion Criteria:

* Is a primary, daily caregiver of a person with CF under the age of 12 enrolled in the study
* Has access to smart device (phone, tablet, etc.) capable of receiving text messages;
* Can complete the Daily Diary on behalf of the child for a total of 42 days (from 14 days pre-VTD to 28 days post-starting VTD);
* Is English-speaking.

Exclusion Criteria:

- Any situation, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.