Response to CFTR Modulators in CF Patients Under 18 Years

Cystic Fibrosis in Children Clinical Trial

— MODUL-CF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04301856
• Other study ID #: 0011928
• Status: Recruiting
• Start date: January 1, 2020
• Est. completion date: January 1, 2026

Study information

• Verified date: March 2021
• Source: Societe Francaise de la Mucoviscidose
• Contact: Stéphane Mazur, PhD
• Phone: 0033427855043
• Email: stephane.mazur[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: January 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis in Children
• Fibrosis

Intervention

Drug:
• CFTR Modulators
CFTR modulators as recommended in routine care by the french health authorities

Locations

Country	Name	City	State
France	Sermet-Gaudelus Isabelle	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Societe Francaise de la Mucoviscidose

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at initiation, as part of national guidelines
Primary	Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 1 year, as part of national guidelines
Primary	Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 3 years, as part of national guidelines
Primary	Lung Imaging	Lung structural injury assessed by Low Dose CT, as part of routine care	at 5 years, as part of national guidelines
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Forced Vital Capacity (FVC)	Forced Vital Capacity (FVC) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	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
Secondary	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
Secondary	Residual Volume (RV)	Residual Volume (RV) in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	Total Pulmonary Capacity	Total Pulmonary Capacity in liter	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	Lung Clearance Index - Lung Clearance Index	Lung clearance of nitrogen	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	colonization of bronchial secretions	bacteria, fungi, mycobacteria	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	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
Secondary	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
Secondary	Abdominal quality of life questionnaire	better score: 0, worse: 25	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	liver ultrasound	liver ultrasound	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	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
Secondary	sweat test	sweat collection	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	intestine inflammation	fecal Calprotectine	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs
Secondary	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
Secondary	side effects: declarative collection and monitoring	declarative collection and monitoring	longitudinal monitoring of assessments carried out as part of routine care during 5 yrs