Lum-Iva-biota: Exploring the Respiratory Mycobiota and Microbiota Profile in French CF Patients Taking Lumacaftor-Ivacaftor

Summary

n2015, VERTEX company - producing already KALYDECO (IVACAFTOR, VX-770) potentiator molecule that is recommended for the treatment of CF patients aged ≥ 6 y, with CFTR mutation altering the channel regulation (class III mutations) as G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549Nou S549R) -was allowed by the Federal Drug Administration (FDA) and European Medicines Agency (EMEA) for producing and using ivacaftor combination (such as lumacaftor/ ivacaftor initially, and more recently tezacaftor/ivacaftor, tezacaftor/ivacaftor/VX-659, tezacaftor/ivacaftor/VX-445 and tezacaftor/ivacaftor/VX-152) in clinical trials for patient with cystic fibrosis, according to age and mutation eligibility criteria.

Since 2016, the French patients homozygous for the p.Phe508del mutation and older than 12 years are able to be treated with the association LUMACAFTOR-IVACAFTOR and this French authorization is being extended for 6-11 years old children (while the European Commission has already granted an extension of the Marketing Authorization for lumacaftor/ivacaftor to include 6-11 years old children with cystic fibrosis since January 2018). Patients treated by lumacaftor/ivacaftor (or other ivacaftor new combinations) are closely monitored according to criteria established by the working group "New Therapeutic Approaches" of the French Society Cystic fibrosis.

This study is a phase IV observational trial for a period of 1 year. In this context, the team aims at initiating a comprehensive monitoring of the lung and gut mycobiota and microbiota evolution under LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) treatment. This project is directly linked to the monitoring of cystic fibrosis patients who begin treatment with LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) in France. The pro- and eukaryotic microbiota analysis is based on the secondary use of sputum and stool samples associated with several clinical data of CF patients under ivacaftor combinations and follow-up during the 1st year of therapy. According to the French law, Lum-Iva-Biota project is a non-interventional study. It aims at demonstrating that changes in the hydration of secretions at the pulmonary and intestinal levels related to LUMACAFTOR-IVACAFTOR therapy (or other new generation of ivacaftor combinations) promote a change in the lung and gut mycobiota and microbiota profiles which may achieve the characteristics of the "healthy type" (in terms of composition, richness and diversity).

Conditions

• Cystic Fibrosis

Interventions

BIOLOGICAL

the lung mycobiota and microbiota profile

All sputum samples will follow regarding mycological and metagenomic analyses as summarized : * Pre-analytical treatment combining pre-treatment with mucolytic agent and sonication action * Separation of the pellet and supernatant, stored at -20 ° C until testing * Galactomannan (GM) Assay on each sputum supernatant to correlate with Aspergillus colonization history * Targeted metagenomics of bacterial communities (based on 16S amplification) and of fungal community (based on ITS2 amplification) * Bioinformatic analysis of metagenomics raw data, correlation with bioclinical data of each patient, statistical analysis, and characterization of phenomena of co-evolution/co-exclusion according to evolutionary ecology concepts. * Pseudomonas aeruginosa load measured by qPCR

BIOLOGICAL

the gut mycobiota and microbiota profile

All stool samples will follow regarding mycological and metagenomic analyses as summarized : - Separation of the pellet and supernatant, stored at -20 ° C until testing - Targeted metagenomics of bacterial communities (based on 16S amplification) and of fungal community (based on ITS2 amplification) - Bioinformatic analysis of metagenomics raw data, correlation with bioclinical data of each patient, statistical analysis, and characterization of phenomena of co-evolution/co-exclusion according to evolutionary ecology concepts. - Measurement of inflammation.

Sponsors & Collaborators

• Societe Francaise de la Mucoviscidose

  collaborator OTHER

• University Hospital, Bordeaux

  lead OTHER

Principal Investigators

• Laurence DELHAES, MD,PhD · University Hospital, Bordeaux

Eligibility

Min Age

2 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-01

Primary Completion

2023-02-28

Completion

2023-02-28

Countries

• France

Study Locations