Clinical trial NCT06683092: Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)
Official title: Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Cystic Fibrosis
Keywords: patient care
adverse events
monitoring
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: Johns Hopkins University
name: Massachusetts General Hospital
name: National Jewish Health
name: Indiana University
name: Children's Hospital Colorado
name: University of Kansas Medical Center
name: Washington University School of Medicine
First posted: 2024-11-12
Enrollment: 200
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female and male people with CF ages 6 and older who are not able to tolerate the standard dose of ETI due to either new/worsening mental health symptoms and/or drug-induced liver injury.

Brief summary: 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 drug-induced liver injury while taking elexacaftor/tezacaftor/ivacaftor (ETI), start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

Detailed description: 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) drug-induced liver injury attributed 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 and intending to take it;
* 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 and intending to take it;
* Experienced drug-induced liver injuary (as defined by local care team) after initiating ETI, which led to one of the following changes in treatment to currently taking:

  1. no modulators; or
  2. a modulator other than ETI; or
  3. 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
* Currently taking VTD
* Unable or unwilling to follow protocol
* If \<12 years old, having another \<12-year-old person in the same household also enrolled in the study
* Is actively listed on any transplant list, or is less than 3 months post-transplant surgery
* Is currently pregnant (test not required)
* Anticipated change in CF Care Centers in the next 6 months.
* Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

RETRIAL-LIVER:

* Cannot access VTD
* Currently taking VTD
* Unable or unwilling to follow protocol
* If \<12 years old, having another \<12-year-old person in the same household also enrolled in the study
* Any severe, decompensated liver disease (e.g. Child-Pugh, Class C)
* Is actively listed on any transplant list, or is less than 3 moths post-transplant surgery (any organ), or had a liver transplant
* Is currently pregnant (test not required)
* Anticipated change in CF Care Centers in the next 6 months.
* Any situation that, 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
* Is able to read and complete surveys and Daily Diary in English.

Exclusion Criteria:

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

Primary outcomes:
measure: RETRIAL-MH: one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening MH symptoms
timeFrame: Day 0 to Month 12
measure: RETRIAL-Liver: one-year incidence of drug-induced liver injury (DILI) with VTD
timeFrame: Day 0 to Month 12
Secondary outcomes:
measure: RETRIAL-MH: Changes in mental health symptoms within the first 6 months
timeFrame: Day 0 to month 6
measure: RETRIAL-Neuro: Changes in neurocognitive symptoms with the 1st month
timeFrame: Day 0 to Day 30
measure: RETRIAL-Liver: one-year incidence of discontinuation or change from VTD standard dosing attributed to liver enzyme elevation.
timeFrame: Day 0 to Month 12
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Wilmington
country: United States
facility: Nemours Children's
state: Delaware
city: Jacksonville
country: United States
facility: Nemours Children's
state: Florida
city: Orlando
country: United States
facility: Nemours Children's
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Bloomington
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University at St. Louis
state: Missouri
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Massachusetts General Hospital
name: Anna Georgiopoulos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: CJ Bathgate, PhD
role: PRINCIPAL_INVESTIGATOR
References: