Mepolizumab Pharmacokinetics Among Patients With Severe Asthma (CESAM)

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University Hospital Center (CHU)

Status

Enrolling

Conditions

Asthma

Treatments

Diagnostic Test: blood sample

Study type

Interventional

Funder types

Other

Identifiers

NCT05495932
RECHMPL 22_0035

Details and patient eligibility

About

Asthma is a chronic disease characterized by inflammation and obstruction of the airways. Identification of the mechanisms of action of corticosteroids has made it possible to define the type 2 inflammation present in nearly 80% of patients with asthma. Monoclonal antibodies (MAb) in severe asthma target type-2 inflammation. Mepolizumab is a humanized IgG1 (immunoglobulin gamma-1) kappa subclass monoclonal antibody directed specifically against interleukin 5 (IL-5). It acts specifically on eosinophil homeostasis, with IL-5 being a key interleukin in eosinophil maturation. The investigators propose to measure the concentrations of mepolizumab in the serum of asthmatic patients treated with this mAb. The investigators hypothesize that the individual pharmacokinetics (PK) of mepolizumab may differ between clinical responders and non-responders.

Full description

Asthma is a chronic disease characterized by inflammation and obstruction of the airways. Understanding the biological effects of the corticosteroids allowed to identify and to define the type 2 inflammation present in nearly 80% of patients with asthma. Monoclonal antibodies (MAb) in severe asthma target type-2 inflammation. Mepolizumab is a humanized IgG1 kappa subclass monoclonal antibody directed specifically against interleukin 5 (IL-5). It acts specifically on eosinophil homeostasis, since IL-5 is a key interleukin in eosinophil maturation. Poor MAb responses can hypothetically arise in situations of poor treatment compliance. And after excluding the latter, several biological mechanisms have been mentioned: i) insufficient bioavailability of the MAb to reach the eosinophils of the bronchial compartment; ii) he development of autoimmunity with the formation of circulating immune complexes; and iii) immunization against mepolizumab, with the formation of neutralizing anti-drug antibodies (ADA). ADA were detected in up to 20% of a treated population and were rarely neutralizing. Interestingly, these ADA could also be detected in naïve populations, suggesting a possible cross-immunization related to previous exposure to MAbs and/or to insufficient assay specificity. In any case, all three possibilities have a common outcome, i.e. decreased circulating concentrations of the MAb in the blood. The investigators propose to measure the concentrations of mepolizumab in the serum of asthmatic patients treated with this mAb. The investigators hypothesize that the individual pharmacokinetics (PK) of mepolizumab may differ between clinical responders and non-responders.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Minimum age: 18 years old
  • History of severe asthma diagnosed by a physician (according to Global Initiative for Asthma (GINA) criteria)
  • Subject on a combination of high-dose (ICS equivalent to 1000 μg beclomethasone) and medium dose inhaled corticosteroid and long acting beta-agonists at least 12 months before inclusion
  • Treatment with mepolizumab in line with the Marketing Authorization
  • Having received at least 6 doses of mepolizumab (monthly subcutaneous administration)
  • Documented initial clinical response to mepolizumab

Exclusion criteria

  • Other respiratory diseases
  • Potential interference from another study
  • Immunosuppressive treatment (i.e methotrexate, polyvalent immunoglobulins, other monoclonal antibody for other condition such as cancer; oral and/or inhaled corticosteroids are allowed)
  • Populations protected according to the French public health code
  • Patient is unavailable, unable or unwilling to attend future visits
  • Non-beneficiary of the French national health insurance system
  • Lack of informed consent

Trial design

Primary purpose

Other

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

50 participants in 1 patient group

Eligible patients
Experimental group
Treatment:
Diagnostic Test: blood sample

Trial contacts and locations

0

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Central trial contact

Anne-Sophie GAMEZ, MD, PhD

Data sourced from clinicaltrials.gov

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