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

• ClinicalTrials.gov Identifier: NCT04732910
• Recruitment Status: Recruiting
• First Posted: February 1, 2021
• Last Update Posted: March 4, 2024
• Sponsor: Charite University, Berlin, Germany
• Collaborators: Hannover Medical School; Heidelberg University; University of Giessen
• Information provided by (Responsible Party): Simon Graeber, Charite University, Berlin, Germany

Tracking Information

• First Submitted Date: January 25, 2021
• First Posted Date: February 1, 2021
• Last Update Posted Date: March 4, 2024
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: March 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 29, 2021)

• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cystic Fibrosis Transmembrane Regulator (CFTR) Biomarker Study to Evaluate the Rescue of Mutant CFTR in Patients With Cystic Fibrosis Treated With CFTR-modulators
• Official Title: CFTR Biomarker Studie Bei Patient*Innen Mit Mukoviszidose Und CFTR-Modulatortherapie
• Brief Summary: 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).
• 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
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Sputum, Blood

• Sampling Method: Non-Probability Sample
• Study Population: Cystic Fibrosis patients
• Condition: Cystic Fibrosis

Intervention

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

observational

• Study Groups/Cohorts: Not Provided

Publications *

• Graeber SY, Renz DM, Stahl M, Pallenberg ST, Sommerburg O, Naehrlich L, Berges J, Dohna M, Ringshausen FC, Doellinger F, Vitzthum C, Rohmel J, Allomba C, Hammerling S, Barth S, Ruckes-Nilges C, Wielputz MO, Hansen G, Vogel-Claussen J, Tummler B, Mall MA, Dittrich AM. Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles. Am J Respir Crit Care Med. 2022 Aug 1;206(3):311-320. doi: 10.1164/rccm.202201-0219OC.
• Graeber SY, Vitzthum C, Pallenberg ST, Naehrlich L, Stahl M, Rohrbach A, Drescher M, Minso R, Ringshausen FC, Rueckes-Nilges C, Klajda J, Berges J, Yu Y, Scheuermann H, Hirtz S, Sommerburg O, Dittrich AM, Tummler B, Mall MA. Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles. Am J Respir Crit Care Med. 2022 Mar 1;205(5):540-549. doi: 10.1164/rccm.202110-2249OC.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 1, 2024): 200
• Original Estimated Enrollment (submitted: January 29, 2021): 90
• Estimated Study Completion Date: December 31, 2027
• Estimated Primary Completion Date: March 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Simon Y Graeber, MD; +4930 450 566 587; simon.graeber@charite.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04732910
• Other Study ID Numbers: 20012746
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Simon Graeber, Charite University, Berlin, Germany
• Original Responsible Party: Same as current
• Current Study Sponsor: Charite University, Berlin, Germany
• Original Study Sponsor: Same as current

Collaborators

• Hannover Medical School
• Heidelberg University
• University of Giessen

Investigators

• Principal Investigator: Simon Y Graeber, MD; Charite University, Berlin, Germany

• PRS Account: Charite University, Berlin, Germany
• Verification Date: March 2024