Response to CFTR Modulators in CF Patients Under 18 Years

NCT ID: NCT04301856

Last Updated: 2021-03-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2026-01-01

Brief 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.

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

Conditions

Cystic Fibrosis in Children

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

CF children treated with CFTR modul

Cystic fibrosis patients under 18 years treated with CFTR modulators according to french health recommendations observational cohort study

CFTR Modulators

Intervention Type: DRUG

CFTR modulators as recommended in routine care by the french health authorities

Interventions

CFTR Modulators

CFTR modulators as recommended in routine care by the french health authorities

Intervention Type: DRUG

Other Intervention Names

Orkambi, Kalydeko...

Eligibility Criteria

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Societe Francaise de la Mucoviscidose

OTHER

Sponsor Role: lead

Responsible Party

Isabelle SERMET-GAUDELUS

Professor Isabelle Sermet-Gaudelus

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Isabelle Sermet-Gaudelus, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Société Francaise de la Mucoviscidose

Locations

Sermet-Gaudelus Isabelle

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Stéphane Mazur, PhD

Role: CONTACT

stephane.mazur@chu-lyon.fr

0033427855043

Anne-Sophie Bonnel, MD

Role: CONTACT

asbonnel@ch-versailles.fr

OO33144494887

Facility Contacts

Isabelle Sermet-Gaudelus, MD PhD

Role: primary

isabelle.sermet@aphp.fr

0033687078403

References

Sermet-Gaudelus I, Letierce A, Berteloot L, Bonnel AS, Chen Y, Makani P, Kelly-Aubert M, Kanoun F, Penalva L, Bouleghem N, Bihouee T, Bui S, Corvol H, Houdouin V, Mittaine M, Tatopoulos A, Weiss L, Wizla N, Kapel N, Bessou A, Tiddens HAWM, Caudri D, Reix P, Marguet C; MODUL-CF study group. Effect of elexacaftor-tezacaftor-ivacaftor on bronchial dilatations in adolescents with cystic fibrosis: a multicentre prospective observational study. Lancet Respir Med. 2025 Oct 22:S2213-2600(25)00248-6. doi: 10.1016/S2213-2600(25)00248-6. Online ahead of print.

Reference Type: DERIVED

PMID: 41138737 (View on PubMed)

Other Identifiers

0011928

Identifier Type: -

Identifier Source: org_study_id