Cystic Fibrosis (CF)
Conditions
Keywords
Cystic Fibrosis, Elexacaftor, Tezacaftor, Ivacaftor, Kaftrio, Kalydeco
Brief summary
The goal of this clinical trial is to support the development of personalized therapy tailored to each patient's individual characteristics. A better understanding of the pharmacokinetic profiles of elexacaftor, tezacaftor, and ivacaftor is essential to support Therapeutic Drug Monitoring (TDM) and to guide dose adjustments when clinically indicated, without compromising therapeutic efficacy. The study will include male and female patients aged ≥6 years with Cystic Fibrosis (CF) carrying at least one F508del mutation and receiving treatment with the elexacaftor/tezacaftor/ivacaftor combination for a sufficient period to achieve steady state. The main objective of the study is to characterize the steady-state plasma concentration profiles of elexacaftor, tezacaftor, and ivacaftor in patients with Cystic Fibrosis treated with the elexacaftor/tezacaftor/ivacaftor combination. Participants will continue their usual treatment with elexacaftor/tezacaftor/ivacaftor and ivacaftor according to the prescribed dosing schedule. During the study, they will attend regular clinical visits every 3 months for up to 12 months. At these visits, blood samples will be collected as part of routine clinical care and used to measure the plasma concentrations of the study drugs. Additional blood samples may be collected after the morning dose to better characterize drug levels over time. In a subset of participants, additional blood samples may be collected at several time points during the day to further assess the pharmacokinetic profile of the drugs. A single additional blood sample may be collected for pharmacogenetic analyses. Participants may also undergo a nasal brushing, as part of routine procedures, to obtain nasal epithelial cells for further analyses. Clinical information, including routine laboratory tests, vital signs, treatment information and any adverse events, will be collected throughout the study. The results of the pharmacokinetic and other laboratory analyses will not be used to modify the participant's treatment, which will remain under the responsibility of the treating physician.
Interventions
Cystic Fibrosis Transmembrane Regulator (CFTR) modulator therapy
Cystic Fibrosis Transmembrane Regulator (CFTR) modulator therapy
Sponsors
Istituto Giannina Gaslini
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cystic Fibrosis patients with at least one F508del mutation treated with the combination elexacaftor/tezacaftor/ivacaftor for a time sufficient to reach steady-state (8 days) * males and females aged ≥6 years * informed consent to participate in the study and to process the patient's personal data obtained prior to the collection of any study data.
Exclusion criteria
* evidence of inadequate compliance to treatment; * pregnancy and/or breastfeeding; * any conditions that may affect the ability to complete informed consent; * any other severe systemic disorders that may compromise the PK parameters; * use of any drug capable of moderately/strongly inhibiting or strongly inducing hepatic biotransformation (see section 4 for details); * denial of the informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentrations of elexacaftor, tezacaftor and ivacaftor at steady-state | [Visit 1 - Day 0] [Visit 2 - Day 90±5] [Visit 3 - Day 180±5] |
Secondary
| Measure | Time frame |
|---|---|
| Population pharmacokinetics (popPK) analysis of elexacaftor, tezacaftor and ivacaftor at steady state | [Visit 1 - Day 0] [Visit 2 - Day 90±5] [Visit 3 - Day 180±5] |
| Harvest of every Adverse Event (AE)/Adverse Drug Reaction (ADR) | [Visit 1 - Day 0] [Visit 2 - Day 90±5] [Visit 3 - Day 180±5] |
| Correlation between pharmacokinetics of elexacaftor, tezacaftor and ivacaftor and number of Adverse Event (AE) | [Visit 1 - Day 0] [Visit 2 - Day 90±5] [Visit 3 - Day 180±5] |
| Correlation between pharmacokinetics and elexacaftor, tezacaftor and ivacaftor efficacy in the 3 groups classifications (responders, non responders and unresolved responders) of elexacaftor, tezacaftor and ivacaftor | [Visit 1 - Day 0] [Visit 2 - Day 90±5] [Visit 3 - Day 180±5] |
Outcome results
None listed