Population Pharmacokinetics of Elexacaftor-tezacaftor-ivacaftor in a Paediatric Population (IMPROVED)

Civil Hospices of Lyon

Status: Not yet enrolling

Conditions: Cystic Fibrosis (CF)

Treatments: Other: There is no intervention as this is a prospective pharmacokinetics study.

Study type: Observational

Funder types: Other

Identifiers

NCT07303621

69HCL25_0708

2025-A01805-44 (Other Identifier)

Details and patient eligibility

About

Cystic fibrosis is a rare, progressive genetic disease caused by a mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Respiratory and nutritional effects are crucial to patients' prognosis. Since the early years of 2010, etiological treatment has been based on the use of CFTRm (CFTR modulator), which aim to restore the function of the mutated protein. Initially used as monotherapy and targeting a limited number of patients, CFTRm has gradually been extended to a larger number of patients, to the point where it now concerns 9 out of 10 patients, through the use of triple therapy with Elexacaftor-Tezacaftor-Ivacaftro (ETI) or Kaftrio(R).

The efficacy of triple therapy is spectacular, revolutionizing the prognosis of the disease. However, the potential for neuropsychological side-effects (20-50% depending on age, but more frequent in young children under 5) and hepatic side-effects (hepatic cytolysis) must be taken into account. A better understanding of pharmacokinetic variability in children, as well as the relationship between exposure to therapeutic effects and adverse reactions, is therefore particularly important.

The aim of this study is to measure the association between the pharmacokinetic parameters of Elexacaftor, Tezacaftor and Ivacaftor (plasma clearance and volume of distribution) and therapeutic or adverse effects in pediatric patients with cystic fibrosis treated with the combination.

Enrollment: 150 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged 2 to 17 years old
• Having Cystic Fibrosis
• Treated by Elexacaftor/Tezacaftor and Ivacaftor (Trikafta® or Kaftrio®)

Exclusion criteria

• Allergy to previous CFTR modulator association (Ivacaftor, lumacaftor)
• Pregnant women
• Patient already enrolled in another study with CYP3A4 inhibitor
• Pulmonary transplant recipient

Trial design

150 participants in 1 patient group

Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics

Treatment:

Other: There is no intervention as this is a prospective pharmacokinetics study.