Response to CFTR Modulators in CF Patients Under 18 Years (MODUL-CF)

Evaluation of the Response to CFTR Modulators in Patients With Cystic Fibrosis Less Than 18 Years of Age

CFTR modulators should improve the prognosis of Cystic Fibrosis. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity is an important medical objective given the potential side effects and the high cost of these molecules.

This observational follow-up cohort study is carried out as part of routine care.

The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy.

The secondary objectives are to evaluate structural impairment at low dose scan at 3 years and 5 years of CFTR modulator treatment, the evolution of respiratory functional parameters, growth, puberty, lung infection, sweat test, quality of life and pancreatic function, as well as tolerance of modulators including liver toxicity.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis in Children
• Intervention / Treatment: Drug: CFTR Modulators

Detailed Description

Cystic fibrosis (CF) is a deadly disease. This is due to overinfected chronic obstructive pulmonary disease that progresses to end-stage respiratory failure. CFTR modulators should improve the prognosis of CF, as they may slow the progression of patients' lung disease. Assessing their impact in the paediatric population is becoming a major issue. Children and adolescents under the age of 18 are a target cohort because they have a lung disease that is still poorly developed. Early prescription of CFTR modulators is therefore a priority but requires evidence of absence of toxicity. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity, is an important medical objective given the potential side effects and the high cost of these molecules.

The outcomes previously used in Phase III studies (FEV1, frequency of exacerbations, nutritional status) are insufficiently sensitive in this population.

Other criteria need to be analyzed to identify the response to CFTR modulators in the short and medium term. The investigators hypothesize that the assessment of pulmonary structural impairment by low-dose lung CT-scan as part of routine care could be a much more sensitive criterion for the development of lung disease under CFTR modulators.

This observational follow-up cohort study is carried out as part of routine care. It does not involve a specific collection for research. Excess bronchial secretions and blood will be kept instead of being discarded in the event of a possible requalification for research.

The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy The secondary objectives are to assess following criteria

• Tolerance of modulators in this age group, including screening for bronchial reactivity at treatment, early liver toxicity
• Longitudinal evolution of pulmonary structural impairment by low dose scan at 3 years and 5 years of CFTR modulator treatment
• Evolution of respiratory functional parameters
• Measurement by spirometry and plethysmography
• Lung clearance index (if possible)
• Longitudinal evolution of bacterial colonization, compared to the year prior to modulating treatment
• Exacerbations: number, duration, days of antibiotics, hospitalizations, return to stable condition
• Colonization of bronchial secretions
• Changes in quality of life
• Evolution of the sweat test
• Longitudinal evaluation of pancreatic function
• Longitudinal evaluation of growth and puberty compared to the year prior to CFTR modulator
• Growth speed, and bone age
• Bone mineralization, body composition (if possible)
• Pubertal markers from 9 years in girls and 10 years in boys
• Evaluation of glycemic dysregulation if present
• Preservation of samples taken as part of routine care (serum, bronchial secretions) for possible research use

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Stéphane Mazur, PhD; Phone Number: 0033427855043; Email: stephane.mazur@chu-lyon.fr
• Study Contact Backup: Name: Anne-Sophie Bonnel, MD; Phone Number: OO33144494887; Email: asbonnel@ch-versailles.fr

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Sermet-Gaudelus Isabelle
    • Contact: Isabelle Sermet-Gaudelus, MD PhD; Phone Number: 0033687078403; Email: isabelle.sermet@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with cystic fibrosis under the age of 18 eligible for CFTR modulator thérapies according to french national recommandations

Description

Inclusion Criteria:

Children with cystic fibrosis under the age of 18 under CFTR modulator therapy

Exclusion Criteria:

• Patients with cystic fibrosis without indication for CFTR modulator therapy
• Patients over the age of 18
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CF children treated with CFTR modul; Cystic fibrosis patients under 18 years treated with CFTR modulators according to french health recommendations observational cohort study	Drug: CFTR Modulators; CFTR modulators as recommended in routine care by the french health authorities; Other Names: Orkambi, Kalydeko...

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at initiation, as part of national guidelines
Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 1 year, as part of national guidelines
Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 3 years, as part of national guidelines
Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 5 years, as part of national guidelines

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
weight in kilogrammes	weight in kilogrammes (associated with a retrospective collection in the year prior to treatment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
height in meters	height in meters (associated with a retrospective collection in the year prior to treatment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
pubertal evolution	pubertal evolution (associated with a retrospective collection in the year prior to treatment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
bronchial infectious exacerbations	bronchial infectious exacerbations (associated with a retrospective collection in the year prior to treatment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Forced Expiratory Volume in 1 second(FEV1)	Forced Expiratory Volume in 1 second(FEV1) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Forced Vital Capacity (FVC)	Forced Vital Capacity (FVC) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Force Expiratory Flow 50 (FEV50)	Force Expiratory Flow 50 (FEV50) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Forced Expiratory Flow 25-75 (FEV25-75)	Forced Expiratory Flow 25-75 (FEV25-75) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Residual Volume (RV)	Residual Volume (RV) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Total Pulmonary Capacity	Total Pulmonary Capacity in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Lung Clearance Index - Lung Clearance Index	Lung clearance of nitrogen	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
colonization of bronchial secretions	bacteria, fungi, mycobacteria	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
quality of life questionnaire	CFQ questionnaire for children above 8 years: worse 0, better 100	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
ENT quality of life questionnaire	SN-score: better score 1, worse 7	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Abdominal quality of life questionnaire	better score: 0, worse: 25	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
liver ultrasound	liver ultrasound	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
elastometry (data available in centers with the necessary equipment)	elastometry (data available in centers with the necessary equipment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
sweat test	sweat collection	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
serum and fecal pancreatic biological markers	immunoreactive trypsin, lipase, amylase, vitamin A and E, Prothrombin time, and fecal (fecal elastase	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
bone biological markers	25OHvitD, Ca, P, PTH, Osteocalcin, IgF1, IgF1BP3, CTX	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
bone maturation	Zscore (in relation to height and sex and weight) (data available in centers with the necessary equipment)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
puberty	serum dosage of FSH, LH, Estradiol, testosterone Pelvic ultrasound if puberty initiated in girls	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
intestine inflammation	fecal Calprotectine	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
glycemic regulation	monitoring of glycemic dysregulation ( as routinely done in the centers)	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
side effects: declarative collection and monitoring	declarative collection and monitoring	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs

Collaborators and Investigators

• Sponsor: Societe Francaise de la Mucoviscidose
• Investigators: Principal Investigator: Isabelle Sermet-Gaudelus, MD PhD, Societe Francaise de la Mucoviscidose

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

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: 0011928

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No