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

Overview

This observational study evaluates the effect of therapy with cystic fibrosis transmembrane regulator (CFTR) modulators on CFTR function measured by the CFTR biomarker intestinal current measurement (ICM), nasal potential difference (NPD) and sweat chloride in a post-approval setting in patients with cystic fibrosis (CF).

Full Title of Study: “CFTR Biomarker Studie Bei Patient*Innen Mit Mukoviszidose Und CFTR-Modulatortherapie”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: March 31, 2027

Detailed Description

Cystic fibrosis transmembrane regulator (CFTR) biomarker (intestinal current measurement (ICM), nasal potential difference (NPD), sweat chloride) before the start of therapy and 12 and 52 weeks after initiation of therapy Clinical parameters (anthropometry, lung function, lung magnetic resonance imaging (MRI), lung computer tomography (CT)) before the start of therapy and after initiation of therapy Assessment of airway secretion specimens before the start of therapy and after initiation of therapy

Interventions

  • Drug: Treatment with cystic fibrosis transmembrane regulator (CFTR) modualtors Ivacaftor, Lumacaftor-Ivacaftor, Tezacaftor-Ivacaftor, Elexacaftor-Tezacaftor-Ivacaftor
    • observational

Clinical Trial Outcome Measures

Primary Measures

  • Intestinal current measurement (ICM)
    • Time Frame: 12 weeks
    • Absolute change from baseline of the chloride secretory ion current induced by cyclic adenosine monophosphate (cAMP) stimulation (forskolin/3-isobutyl-1-methylxanthine (IBMX)) in rectal tissue determined by intestinal current measurement (ICM) as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker

Secondary Measures

  • Forced expiratory volume in 1 second (FEV1)
    • Time Frame: 12, 52, 104 weeks
    • Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) in spirometry
  • Nasal potential Difference (NPD)
    • Time Frame: 12 weeks
    • 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
  • Sweat chloride
    • Time Frame: 12, 52, 104 weeks
    • Absolute change from baseline of the chloride concentration in Gibson-Cooke pilocarpine iontophoresis sweat test as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker
  • Lung clearance index (LCI)
    • Time Frame: 12, 52, 104 weeks
    • Absolute change from baseline of the lung clearance index (LCI)
  • Lung magnetic resonance imaging (MRI)
    • Time Frame: 12, 52, 104 weeks
    • 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)
  • Lung computer tomography
    • Time Frame: 52, 104 weeks
    • 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)
  • Paranasal sinus magnetic resonance imaging (MRI)
    • Time Frame: 12, 52, 104 weeks
    • 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)
  • Fecal elastase
    • Time Frame: 12, 52, 104 weeks
    • Absolute change from baseline in fecal elastase-1 (FE-1) levels
  • Weight
    • Time Frame: 12, 52, 104 weeks
    • Absolute change from baseline in weight
  • Airway Microbiome
    • Time Frame: 4, 12, 52, 104 weeks
    • Absolute change in shannon index representing the alpha-diversity in sputum samples
  • Sputum Elasticity
    • Time Frame: 4, 12, 52, 104 weeks
    • Absolute change in the elastic modulus (G’) in sputum samples measured with a rheometer
  • Sputum Viscocity
    • Time Frame: 4, 12, 52, 104 weeks
    • Absolute change in the viscous modulus (G”) in sputum samples measured with a rheometer

Participating in This Clinical Trial

Inclusion Criteria

  • Decision for cystic fibrosis (CF) transmembrane regulator (CFTR)-modulator therapy by the patient and the caring CF physician – Signed informed consent form (ICF) and, where appropriate, signed assent form. Exclusion Criteria:

  • Ongoing participation in an investigational drug study (including studies investigating lumacaftor, tezacaftor or ivacaftor)

Gender Eligibility: All

Minimum Age: 6 Months

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Charite University, Berlin, Germany
  • Collaborator
    • Hannover Medical School
  • Provider of Information About this Clinical Study
    • Principal Investigator: Simon Graeber, BIH Clinician Scientist – Charite University, Berlin, Germany
  • Overall Official(s)
    • Simon Y Graeber, MD, Principal Investigator, Charite University, Berlin, Germany
  • Overall Contact(s)
    • Simon Y Graeber, MD, +4930 450 566 587, simon.graeber@charite.de

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