Airway Remodeling During Mepolizumab Treatment

NCT03797404 | Completed

• 2 other identifiers: P180501J2018-002591-40
• Study Type: observational
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic airway changes, such as smooth muscle hypertrophy/hyperplasia, reticular basement membrane (RBM) thickening, goblet cells hyperplasia characterize severe asthma. Chronic inflammation, and especially eosinophilia and T2 cytokines are involved in these structural changes. The aim of this prospective observational study is to assess airway changes, assessed by bronchial biopsies before treatment, then after 6 months and 12 months, induced by mepolizumab in 40 severe asthma patients who will receive the treatment as part of their standard care. Changes in RBM thickening, in airway smooth muscle (ASM) area, in the number of PGP9 sections will be assessed on bronchial biopsies after 6 months and 12 months of mepolizumab treatment. Bronchoalveolar lavage (BAL) levels of inflammatory and remodeling mediators and of extra-cellular matrix (ECM) components will be measured after 6 months and 12 months of mepolizumab treatment. Relationship between clinical response to mepolizumab and remodeling changes after 6 months and 12 months will be assessed.

Conditions

Asthma

Keywords

Eosinophil; Bronchial biopsies; Mepolizumab; Severe

Outcome Measures

Primary Outcomes (8)

• Changes in reticular basement membrane (RBM) thickening

  The absolute variation in RBM thickening (µm, morphometry measurement on bronchial biopsies) over 12 months is defined as the difference between month twelve and baseline (V1). The absolute variation in RBM thickening over 6 months is defined as the difference between month six and baseline (V1).

  0, 6 and 12 months

• Changes in airway smooth muscle (ASM) area

  Measured in morphometry in µm2 and expressed as a percentage of smooth muscle surface area relative to the biopsy surface. The absolute variation in ASM area over 12 months is defined as the difference between month twelve and baseline (V1). The absolute variation in ASM area over 6 months is defined as the difference between month six and baseline (V1).

  0, 6 and 12 months

• Number of proliferating muscle cells

  Evaluated by anti proliferating cell nuclear antigen (PCNA) antibodies, expressed as the number of positive cells per muscle surface.

  0, 6 and 12 months

• Number of nerve endings

  Evaluated by PGP9 and expressed as number of positive cells per biopsy surface in mm2

  0, 6 and 12 months

• Number of vascular sections

  Measured with an anti-CD31 antibody, expressed in number of sections per mm2.

  0, 6 and 12 months

• Number of infiltrating inflammatory cells in the biopsies

  Number of infiltrating inflammatory cells (infiltrating neutrophils, lymphocytes and eosinophils) expressed as number of positive cells per biopsy surface in mm2

  0, 6 and 12 months

• Number of inflammatory cells in the BAL

  Number of inflammatory cells (neutrophils, lymphocytes and eosinophils) expressed as % of total cells in the BAL

  0, 6 and 12 months

• Proportion of eosinophils expressing MBP/IL3R

  Measured on bronchial biopsies, expressed as number of cells per biopsy surface in mm2

  0, 6 and 12 months

Secondary Outcomes (25)

• Interferon-gamma concentration

  0, 6 and 12 months

• IL-13 concentration

  0, 6 and 12 months

• Periostin concentration

  0, 6 and 12 months

• IL-17A concentration

  0, 6 and 12 months

• IL-22 concentration

  0, 6 and 12 months

Study Arms (2)

Mepolizumab

Patients receiving mepolizumab

Patients w/o mepolizumab (retrospective)

Retrospective control group of patients not exposed to mepolizumab, included in the COBRA cohort and the ASMATHERM protocol, who had 2 sets of biopsies and BAL within a 6 to 12 month-interval, without change in their treatment. Clinical data for this patients are available at inclusion and after 12 months.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with severe uncontrolled eosinophil asthma with an indication for mepolizumab according to French recommandations (eos \>300mm3 in the previous year, \>2 exacerbations, despite optimal step 4-5 therapy, including daily use of steroids).

You may qualify if:

• adult \>18 years,
• severe uncontrolled asthma, defined as eosinophil blood count \>300/mm3 in the previous 12 months and at least 2 exacerbations in the previous 12 months or requiring oral steroids for more than half of the previous year,
• indication for mepolizumab decided by an asthma specialist,
• efficient contraception, for women of reproductive age

You may not qualify if:

• pregnancy,
• smokers or ex smokers \>10 pack/yr,
• contra indication for fiberoptic bronchoscopy (allergy to xylocain, antiaggregant or anticoagulant treatment...),
• contra indication for mepolizumab,
• participation in another interventional trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• GlaxoSmithKline: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Bichat hospital

Paris, 75018, France

Location

Related Publications (1)

• Taille C, Hamidi F, Heddebaut N, Pote N, Le Guen P, Le Brun M, Roy C, Dupont A, Letuve S. Impact of Mepolizumab on Airway Remodeling and Inflammation in Severe Eosinophilic Asthma. Chest. 2025 Dec 5:S0012-3692(25)05814-3. doi: 10.1016/j.chest.2025.10.047. Online ahead of print.

  PMID: 41354402 DERIVED

MeSH Terms

Conditions

Asthma; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Study Officials

• Camille TAILLE, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: January 9, 2019
• Study Start: April 24, 2019
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: January 20, 2023

Record last verified: 2023-01

Locations

FR (1)