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

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.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis (CF)
• Intervention / Treatment: Other: There is no intervention as this is a prospective pharmacokinetics study.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Romain GARREAU, PharmD.; Phone Number: +33 4 72 07 19 28; Email: romain.garreau@chu-lyon.fr
• Study Contact Backup: Name: Philippe REIX, M.D., Ph.D; Phone Number: +33 4 27 85 54 70; Email: philippe.reix@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69029
    • Recruiting
    • Hôpital Femme Mère Enfant (HFME)
    • Contact: Philippe REIX, M.D.; Phone Number: +33 4 27 85 54 70; Email: philippe.reix@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study population is from a tertiary care hospital. Children enrolled in the study are followed in the referral center for pediatric cystic fibrosis.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics	Other: There is no intervention as this is a prospective pharmacokinetics study.; There is no intervention as this is a prospective pharmacokinetics study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor	Measure residual concentration of Elexacaftor, Ivacaftor and Tezacaftor	5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Maximum Plasma Concentration [Cmax]	Measured Cmax of Elexacaftor, Ivacaftor and Tezacaftor	5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Area Under the Concentration Time Curve between two administrations of Elexacaftor, Ivacaftor and Tezacaftor	Area under the concentration time curve between two administrations of (AUC0-tz) of Elexacaftor, Ivacaftor and Tezacaftor	5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number (Proportion) of Subjects with adverse events	Specific drug related adverse events such as hepatic impairment or neurocomportmental disorder will be monitored. All safety data will be analysed using descriptive statistics. Pharmacokinetics analysis will be used to monitor existing relationship between elexacaftor/tezacaftor and ivacaftor	5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Relationship between Pharmacokinetics and Cystic Fibrosis mutational status and Adverse Event		5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Relationship between Pharmacokinetics/Toxixodynamic and Cystic Fibrosis mutational status		5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations	Area Under the Effect Time curve (AUEC) of Lung Clearance Index 2.5	5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Area Under the Effect Time curve (AUEC) of Sweat Chloride		5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2026
• Primary Completion (Estimated): August 9, 2027
• Study Completion (Estimated): August 9, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: pharmacokinetics; Cystic Fibrosis; Trikafta; Ivacaftor; Elexacaftor
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: 69HCL25_0708; 2025-A01805-44 (Other Identifier: N° ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No