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

Boston Children's Hospital

Status: Invitation-only

Conditions: Cystic Fibrosis

Treatments: Other: RETRIAL-MH; Other: RETRIAL-Neuro; Other: RETRIAL-Liver

Study type: Observational

Funder types: Other

Identifiers

NCT06683092

IRB-P00050262

Details and patient eligibility

About

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).

Full 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).

Enrollment: 200 estimated patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 3 patient groups

RETRIAL-MH

Description:

People with CF ages 6 and up with a history of new or worsening mental health symptoms (MH) while on elexacaftor/tezacaftor/ivacaftor (ETI) requiring discontinuation or change from standard dosing who start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

Treatment:

Other: RETRIAL-MH

RETRIAL-Neuro

Description:

People with CF from RETRIAL-MH who experienced new/worsening neurocognitive symptoms while taking elexacaftor/tezacaftor/ivacaftor (ETI).

Treatment:

Other: RETRIAL-Neuro

RETRIAL-Liver

Description:

People with Cystic Fibrosis ages 6 and up with a history of drug-induced liver injury attributed to elexacaftor/tezacaftor/ivacaftor (ETI) requiring dose modification or discontinuation start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

Treatment:

Other: RETRIAL-Liver