Modulate-CF: Cystic Fibrosis Transmembrane Regulator (CFTR) Biomarker Study to Evaluate the Rescue of Mutant CFTR in Patients With Cystic Fibrosis Treated With CFTR-modulators

Forced expiratory volume in 1 second (FEV1)

Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) in spirometry

Time frame: quaterly in the first year, yearly thereafter up to 5 years

Nasal potential Difference (NPD)

Absolute change from baseline total chloride response (zero chloride and isoproterenol) in nasal potential Difference (NPD) as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker

Time frame: 12 weeks

Sweat chloride

Absolute change from baseline of the chloride concentration in Gibson-Cooke pilocarpine iontophoresis sweat test as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker

Time frame: 12, 52 weeks, yearly thereafter up to 5 years

Lung clearance index (LCI)

Absolute change from baseline of the lung clearance index (LCI)

Time frame: quaterly in the first year, yearly thereafter up to 5 years

Lung magnetic resonance imaging (MRI)

Absolute change from baseline in lung magnetic resonance imaging (MRI) score (Heidelberg MRI score ranging from 0 to 72 with higher values associated with worsening of the outcome; Eichinger et al. Eur J Radiol 2012)

Time frame: 12, 52 weeks, yearly thereafter up to 5 years

Lung computer tomography

Absolute change from baseline in lung computer tomography (CT) score (Brody score ranging from 0 to 40,5 with higher values associated with worsening of the outcome; Brody et al. J Thorac Imaging 2006)

Time frame: 52, 104 weeks

Paranasal sinus magnetic resonance imaging (MRI)

Absolute change from baseline in paranasal sinus magnetic resonance imaging (MRI) score (Sinunasal MRI score ranging from 0 to 68 with higher values associated with worsening of the outcome; Sommerburg et al. Ann Am Thorac Soc 2020)

Time frame: 12, 52 weeks, yearly thereafter up to 5 years

Fecal elastase

Absolute change from baseline in fecal elastase-1 (FE-1) levels

Time frame: 12, 52 weeks, yearly thereafter up to 5 years

Weight

Absolute change from baseline in weight

Time frame: quaterly in the first year, yearly thereafter up to 5 years

Airway Microbiome

Absolute change in shannon index representing the alpha-diversity in sputum samples

Time frame: 4, 12, 52 weeks, yearly thereafter up to 5 years

Sputum Elasticity

Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer

Time frame: 4, 12, 52 weeks, yearly thereafter up to 5 years

Sputum Viscocity

Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer

Time frame: 4, 12, 52 weeks, yearly thereafter up to 5 years

Cystic Fibrosis Questionnaire-Revised (CFQ-R)

The Cystic Fibrosis Questionnaire-Revised is a disease-specific health-related quality of life instrument for individuals with cystic fibrosis. Scores are standardized on a 0-100 scale. Minimum: 0; Maximum: 100. Higher scores indicate better health-related quality of life. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Patient Health Questionnaire-9 (PHQ-9)

The Patient Health Questionnaire-9 is a 9-item self-report measure assessing depressive symptom severity over the past two weeks. Total score range: 0-27. Minimum: 0; Maximum: 27. Higher scores indicate more severe depressive symptoms. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Generalized Anxiety Disorder-7 (GAD-7)

The Generalized Anxiety Disorder-7 is a 7-item self-report measure assessing anxiety symptom severity over the past two weeks. Total score range: 0-21. Minimum: 0; Maximum: 21. Higher scores indicate more severe anxiety symptoms. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5)

The Child Behavior Checklist for Ages 1½-5 is a parent-reported measure assessing emotional and behavioral problems in children aged 18 months to 5 years. The Total Problems raw score ranges from 0-198. Minimum: 0; Maximum: 198. Higher scores indicate more emotional and behavioral problems. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Child Behavior Checklist for Ages 6-18 (CBCL/6-18)

The Child Behavior Checklist for Ages 6-18 is a parent-reported measure of emotional and behavioral problems. Raw total problem scores range from 0-226. Minimum: 0; Maximum: 226. Higher scores indicate more behavioral and emotional problems. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Youth Self-Report for Ages 11-18 (YSR/11-18)

The Youth Self-Report for Ages 11-18 is a self-report measure of emotional and behavioral problems, corresponding to the Child Behavior Checklist. Raw total problem scores range from 0-224. Minimum: 0; Maximum: 224. Higher scores indicate more behavioral and emotional problems. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

Strengths and Difficulties Questionnaire (SDQ)

The Strengths and Difficulties Questionnaire is a behavioral screening questionnaire. The Total Difficulties Score ranges from 0-40. Minimum: 0; Maximum: 40. Higher scores indicate more emotional and behavioral difficulties. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years

22-Item Sino-Nasal Outcome Test (SNOT-22)

The 22-Item Sino-Nasal Outcome Test assesses symptom severity and health-related quality of life in sinonasal disease. The total score ranges from 0-110. Minimum: 0; Maximum: 110. Higher scores indicate more severe symptoms and poorer quality of life. Absolute change from baseline is calculated as follow-up score minus baseline score.

Time frame: quarterly in the first year, yearly thereafter up to 5 years