Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    remomepo
Previous Study | Return to List | Next Study

Airway Remodeling During Mepolizumab Treatment (REMOMEPO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03797404
Recruitment Status : Recruiting
First Posted : January 9, 2019
Last Update Posted : January 25, 2022
Sponsor:
Collaborators:
GlaxoSmithKline
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease
Asthma

Show Show detailed description

Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 12 Months
Official Title: Airway Remodeling Changes Induced by Mepolizumab in Severe Eosinophil Asthma
Actual Study Start Date : April 24, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : June 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Mepolizumab

Group/Cohort
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.



Primary Outcome Measures :
  1. Changes in reticular basement membrane (RBM) thickening [ Time Frame: 0, 6 and 12 months ]

    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).


  2. Changes in airway smooth muscle (ASM) area [ Time Frame: 0, 6 and 12 months ]

    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).


  3. Number of proliferating muscle cells [ Time Frame: 0, 6 and 12 months ]
    Evaluated by anti proliferating cell nuclear antigen (PCNA) antibodies, expressed as the number of positive cells per muscle surface.

  4. Number of nerve endings [ Time Frame: 0, 6 and 12 months ]
    Evaluated by PGP9 and expressed as number of positive cells per biopsy surface in mm2

  5. Number of vascular sections [ Time Frame: 0, 6 and 12 months ]
    Measured with an anti-CD31 antibody, expressed in number of sections per mm2.

  6. Number of infiltrating inflammatory cells in the biopsies [ Time Frame: 0, 6 and 12 months ]
    Number of infiltrating inflammatory cells (infiltrating neutrophils, lymphocytes and eosinophils) expressed as number of positive cells per biopsy surface in mm2

  7. Number of inflammatory cells in the BAL [ Time Frame: 0, 6 and 12 months ]
    Number of inflammatory cells (neutrophils, lymphocytes and eosinophils) expressed as % of total cells in the BAL

  8. Proportion of eosinophils expressing MBP/IL3R [ Time Frame: 0, 6 and 12 months ]
    Measured on bronchial biopsies, expressed as number of cells per biopsy surface in mm2


Secondary Outcome Measures :
  1. Interferon-gamma concentration [ Time Frame: 0, 6 and 12 months ]
    Interferon-gamma (Th1 cytokine) will be measured in BAL and serum

  2. IL-13 concentration [ Time Frame: 0, 6 and 12 months ]
    IL-13 (Th2 cytokine) will be measured in BAL and serum

  3. Periostin concentration [ Time Frame: 0, 6 and 12 months ]
    Periostin (Th2 cytokine) will be measured in BAL and serum

  4. IL-17A concentration [ Time Frame: 0, 6 and 12 months ]
    IL-17A (Th17 cytokine) will be measured in BAL and serum

  5. IL-22 concentration [ Time Frame: 0, 6 and 12 months ]
    IL-22 (Th17 cytokine) will be measured in BAL and serum

  6. IL-33 concentration [ Time Frame: 0, 6 and 12 months ]
    IL-33 (innate immune cytokines) will be measured in BAL and serum

  7. Thymic Stromal Lymphopoietin (TSLP) concentration [ Time Frame: 0, 6 and 12 months ]
    TSLP (innate immune cytokines) will be measured in BAL and serum

  8. Fibronectin concentration [ Time Frame: 0, 6 and 12 months ]
    Fibronectin (soluble hallmarks of ECM remodeling) will be measured in BAL and serum

  9. Tenascin concentration [ Time Frame: 0, 6 and 12 months ]
    Tenascin (soluble hallmarks of ECM remodeling) will be measured in BAL and serum

  10. Fibulin-1 concentration [ Time Frame: 0, 6 and 12 months ]
    Fibulin-1 (soluble hallmarks of ECM remodeling) will be measured in BAL and serum

  11. Monocyte chemoattractant protein-1 (CCL/MCP-1) concentration [ Time Frame: 0, 6 and 12 months ]
    Will be measured in BAL and serum

  12. EGF concentration [ Time Frame: 0, 6 and 12 months ]
    Will be measured in BAL and serum

  13. bFGF concentration [ Time Frame: 0, 6 and 12 months ]
    Will be measured in BAL and serum

  14. PDGF-BB concentration [ Time Frame: 0, 6 and 12 months ]
    Will be measured in BAL and serum

  15. Total score at Asthma Control Test [ Time Frame: 0, 6 and 12 months ]

    Measured using the Asthma Control Test (ACT) scale (range: 5 to 25). ACT assesses the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control.

    • 5 items, with 4-week recall (on symptoms and daily functioning)
    • each item is evaluated by a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).

    The total score ranges from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score >19 indicates well-controlled asthma.


  16. Global evaluation of mepolizumab benefit [ Time Frame: 6 and 12 months ]

    Benefit of mepolizumab will be evaluated by patient and by physician according to the physician's Global Evaluation of Treatment Effectiveness (GETE).

    Patients will be considered as "responders" if classified as "excellent response" or "good response" by their physician.


  17. Forced expiratory volume (FEV1) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in ml.

  18. Forced expiratory volume (FEV1) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in % of predicted value.

  19. Forced expiratory volume/Vital capacity (FEV1/VC) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in %

  20. Total lung capacity (TLC) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in ml.

  21. Total lung capacity (TLC) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in % of predicted value.

  22. Residual volume (RV) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in ml.

  23. Residual volume (RV) [ Time Frame: 0, 6 and 12 months ]
    Measured during lung function test, pre/post salbutamol, expressed in % of predicted value.

  24. Proportion of patients with pre-bronchodilator FEV1 greater than 80% [ Time Frame: 6 and 12 months ]
    In order to assess functional response to treatment

  25. Proportion of patients with an increase from baseline in pre-bronchodilator FEV1 greater than 20% [ Time Frame: 6 and 12 months ]
    In order to assess functional response to treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Criteria

Inclusion criteria:

  • 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

Exclusion criteria :

  • pregnancy,
  • smokers or ex smokers >10 pack/yr,
  • contra indication for fiberoptic bronchoscopy (allergy to xylocain, antiaggregant or anticoagulant treatment...),
  • contra indication for mepolizumab,
  • patient who previously received mepolizumab or already received mepolizumab at inclusion,
  • participation in another interventional trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03797404


Contacts
Layout table for location contacts
Contact: Camille TAILLE, MD, PhD +33140456863 camille.taille@aphp.fr

Locations
Layout table for location information
France
Bichat hospital Recruiting
Paris, France, 75018
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
GlaxoSmithKline
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Layout table for investigator information
Principal Investigator: Camille TAILLE, MD, PhD Assistance Publique - Hôpitaux de Paris
Additional Information:

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03797404    
Other Study ID Numbers: P180501J
2018-002591-40 ( EudraCT Number )
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: January 25, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Eosinophil
Bronchial biopsies
Mepolizumab
Severe
Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Airway Remodeling
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathological Conditions, Anatomical