Real-world Efficacy and Safety of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy in Adult Patients With Cystic Fibrosis (CF)

Study Overview
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Brief Summary
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In this trial real-world data on the safety (side effects and medication interactions) and efficacy (evolution of lung function testing, chronic bacterial airway infection, quality of life and endo- and exocrine pancreatic function) will be collected in adult people with cystic fibrosis (pwCF) eligible for elexacaftor-tezacaftor-ivacaftor (ETI) up until 2 years after the start of this therapy.

Detailed Description
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PwCF group A: CFTR-modulator-naive pwCF eligible for ETI (based on age and CFTR genotype) PwCF group B: pwCF already on CFTR modulating therapy (i.e. ivacaftor-lumacaftor or ivacaftor-tezacaftor) and switching to ETI. Patients in both groups will undergo these examinations: Physical examination (including weight) Anamnesis for current and recent medication use (including dosage of pancreatic enzymes) and for acute respiratory exacerbations Lung function testing including spiometry, multiple breath washout testing and fractional exhaled nitric oxide Blood sampling: liver function tests, creatine kinase, albumin, PT, red and white blood cell count, platelet count Sputum/cough swab sampling fecal elastase measurement Cystic fibrosis questionnaire-revised (CFQ-R) questionnaire Patient health questionnaire-9 (PHQ-9) questionnaire General anxiety disorder-7 (GAD-7) questionnaire Sino-nasal outcome test-22 (SNOT-22) questionnaire These will be performed at baseline (prior to the start of ETI, on the same day of start of ETI), and every 3 months (+/- 7 days) thereafter. A blood sample will also be performed 14 (+/- 7 days) days after start of ETI (for safety). Fecal elastase measurement will only be performed at baseline if not available in the patient's medical record, and only 6 months after start of ETI.

Official Title
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Real-world Efficacy and Safety of CFTR Modulator Therapy in Adult Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Diagnostic Test: CFQ-R questionnaire, SNOT-22 questionnaire, fecal elastase measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: eligible for ETI (i.e. age above 18 years and CFTR genotype F508del/any) based on reimbursement criteria in Belgium Exclusion Criteria: inability to perform lung function testing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ETI<br>pwCF which are CFTR-modulator naive and pwCF previously treated with a CFTR-modulator (i.e. tezacaftor-ivacaftor or lumacaftor-ivacaftor) will undergo standard-of-care examinations as well as examinations in the context of this trial (i.e. CFQ-R, PHQ-9, GAD-7 and SNOT-22 questionnaires, fecal elastase measurement) | Diagnostic Test: CFQ-R questionnaire, SNOT-22 questionnaire, fecal elastase measurement<br>* cf supra<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percent predicted forced expiratory volume in 1 second (ppFEV1) |  | 2 years | 
| Lung clearance index (LCI) |  | 2 years | 
| Fractional excretion of nitric oxide (FeNO) |  | 2 years | 
| CFQ-R questionnaire |  | 2 years | 
| fecal elastase (microgram per gram of feces) | the concentration of elastase (a pancreatic enzyme) in feces before and 6 months after start of CFTR modulating treatment, as a surrogate measure for pancreatic function | 2 years | 
| the amount of participants experiencing a treatment-related adverse event |  | 2 years | 
| annual acute exacerbation rate |  | 2 years | 
| body mass index (BMI) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT-22 questionnaire |  | 2 years | 
| GAD-7 questionnaire |  | 2 years | 
| PHQ-9 questionnaire |  | 2 years | 
| aerobic culture on sputum or cough swab sample |  | 2 years | 
| dosage of pancreatic enzyme replacement therapy |  | 2 years |