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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Diagnostic test: CFQ-R questionnaire, SNOT-22 questionnaire, fecal elastase measurement

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 85
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefanie Vincken, M.D.; Phone Number: +32 2 477 68 41; Email: stefanie.vincken@uzbrussel.be
• Study Contact Backup: Name: Eef Vanderhelst, M.D. Ph.D.; Phone Number: +32 2 477 68 41; Email: eef.vanderhelst@uzbrussel.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ETI; 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; cf supra

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: BUN1432021000472

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes