AsthmaCESAMNCT05495932
Mepolizumab Pharmacokinetics Among Patients With Severe Asthma
A study testing blood sample in people with Asthma, run by University Hospital, Montpellier at 2 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesFrance
- Study dates
- 15 Nov 2022to 20 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country.
France2 sites
university Hospital of Montpellier
Montpellier, France, 34295
University Hospital of Tours
Tours, France, 37044
About this study
Official title: Mepolizumab Pharmacokinetics Among Patients With Severe Asthma: Protocol for a Case Control Study Comparing Clinical Responders Versus Non Responders
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.
Read the detailed 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.
- Conditions
- Asthma
- Being tested
- blood sample
- Keywords
- Severe asthma, Mepolizumab, Biologics, Response, Pharmacokinetics
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleDiagnostic test
blood sample taken to measure serum mepolizumab concentration at baseline, 1 month and 6 months during study follow-up
| Study group | Role | What they receive |
|---|---|---|
| Eligible patients | Experimental | Not described Receives: Diagnostic Test: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mepolizumab serum concentration
The primary outcome is the change in trough concentration of mepolizumab in serum at 1-month post-enrolment. Mepolizumab serum concentration will be determine by ELISA
Measured: 1 month
Secondary outcomes (11)
Mepolizumab serum concentration
Mepolizumab serum concentration will be determine by ELISA.
Measured: 6 months
Complete blood cell count at 1 month
comparison of number and % of eosinophils, basophils, neutrophils between responders and non-responders at baseline and 1-month
Measured: 1 month
Complete blood cell count at 6 months
comparison of number and % of eosinophils, basophils, neutrophils between responders and non-responders for the six-month follow-up period
Measured: 6 months
Comparison of lung function by airway obstruction
To describe the degree of airway obstruction, forced expiratory volume in one second (FEV1) and forced vital capacity will be measured using spirometry. The quantitative variables FEV1 and FEV1/FVC (Forced Vital Capacity) will be compared between responders and non-responders for the six-month follow-up period
Measured: 6 months
Comparison of asthma control by ACQ-6 score
Asthma control in terms of symptoms will be assessed by the six-item Asthma Control Questionnaire (ACQ-6). The ACQ-6 scores will be compared between responders and non-responders for the six-month follow-up period.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses.
A score of 1.5 or more on the 6-item Asthma Control Questionnaire (ACQ-6) indicates that a patient has inadequate asthma control.
Measured: 6 months
Comparison of chronic rhinosinusitis by SNOT-22 score
The sino-nasal outcomes for chronic rhinosinusitis will be assessed by the 22-item sino-nasal outcome test (SNOT-22). The SNOT-22 scores will be compared between responders and non-responders for the six-month follow-up period.
The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110. Higher scores indicate poorer outcomes.
Measured: 6 months
Comparison of exacerbation rate
Number, dates, and severity of exacerbations as defined by the Global Asthma Initiative (GINA) will be collected throughout the follow-up period. The number of exacerbations, the exacerbations rate and the number of days not exacerbating will be compared between responders and non-responders.
Measured: 6 months
Number of days alive and not exacerbating
Measured: 6 months
Comparison of change in oral corticosteroid
Oral corticosteroid use will be collected throughout the follow-up period. The % decrease of the initial corticosteroid therapy will be compared between responders and non-responders at 6 months.
Measured: 6 months
Presence/absence of a >50% reduction in exacerbation rate
Measured: 6 months
Presence/absence of monoclonal antibody switching
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2022
- Study start15 Nov 2022
- Primary completion20 Dec 2024
- Study completion20 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Case-control study including adult patients with severe asthma successfully treated with mepolizumab for at least 24 weeks, and then divided into two groups at inclusion : responders and non-responders according to the results of blood samples taken at inclusion, 1 month and 6 months during study follow-up The clinical criteria used to define a complete response to mepolizumab are : Reduction of maintenance corticotherapy \> 50% reduction OR dose \>5mg/day; Reduction of exacerbation rate by \> 50%; ACQ-6 score \< 1.5 and no increase in score \> 0.5 since enrolment Patients lacking any one of the previous criteria are classified as non-responders. Clinical response criteria are evaluated at each study visit, and the final classification at 6 months post-inclusion determines study groups to be matched and compared during statistical analyses
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne-Sophie GAMEZ, MD, PhD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05495932
- Sponsor's protocol ID
- RECHMPL22_0035
- Other IDs
- 2022-A00982-41
- Acronym
- CESAM
- Status last verified
- Jan 2025
- First submitted
- 8 Aug 2022
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study. Data will be made available to persons who address a reasonable request to the study director. Individual participant data (and an accompanying data dictionary) will be de-identified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity. The following will also be made available to the public at https://osf.io/a5cdg/ as soon as feasible: * The study protocol (will preferably be published in a journal; alternatively, it can be posted to https://osf.io/a5cdg/); * Participant information materials; * The paper form for the eCRF; * The data sharing plan.
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mepolizumab Pharmacokinetics Among Patients With Severe Asthma: Protocol for a Case Control Study Comparing Clinical Responders Versus Non Responders
- ClinicalTrials.gov ID
- NCT05495932
- Acronym / sponsor ID
- CESAM / RECHMPL22_0035
- Conditions
- Asthma
- Keywords
- Severe asthma, Mepolizumab, Biologics, Response, Pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 15 Nov 2022 (actual)
- Primary completion
- 20 Dec 2024 (actual)
- Study completion
- 20 Dec 2024 (actual)
- First posted
- 10 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Case-control study including adult patients with severe asthma successfully treated with mepolizumab for at least 24 weeks, and then divided into two groups at inclusion : responders and non-responders according to the results of blood samples taken at inclusion, 1 month and 6 months during study follow-up The clinical criteria used to define a complete response to mepolizumab are : Reduction of maintenance corticotherapy > 50% reduction OR dose >5mg/day; Reduction of exacerbation rate by > 50%; ACQ-6 score < 1.5 and no increase in score > 0.5 since enrolment Patients lacking any one of the previous criteria are classified as non-responders. Clinical response criteria are evaluated at each study visit, and the final classification at 6 months post-inclusion determines study groups to be matched and compared during statistical analyses
| Arm | Type | Receives |
|---|---|---|
| Eligible patients | Experimental | Diagnostic Test: blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sampleblood sample taken to measure serum mepolizumab concentration at baseline, 1 month and 6 months during study follow-up | Diagnostic test | Eligible patients |
Primary outcome
Change in Mepolizumab serum concentration
Time frame: 1 month
The primary outcome is the change in trough concentration of mepolizumab in serum at 1-month post-enrolment. Mepolizumab serum concentration will be determine by ELISA
11 secondary outcomes
Mepolizumab serum concentration
Time frame: 6 months
Complete blood cell count at 1 month
Time frame: 1 month
Complete blood cell count at 6 months
Time frame: 6 months
Comparison of lung function by airway obstruction
Time frame: 6 months
Comparison of asthma control by ACQ-6 score
Time frame: 6 months
Comparison of chronic rhinosinusitis by SNOT-22 score
Time frame: 6 months
Comparison of exacerbation rate
Time frame: 6 months
Number of days alive and not exacerbating
Time frame: 6 months
Comparison of change in oral corticosteroid
Time frame: 6 months
Presence/absence of a >50% reduction in exacerbation rate
Time frame: 6 months
Presence/absence of monoclonal antibody switching
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2025.
- Individual participant dataSharing planned: Yes. The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study. Data will be made available to persons who address a reasonable request to the study director. Individual participant data (and an accompanying data dictionary) will be de-identified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity. The following will also be made available to the public at https://osf.io/a5cdg/ as soon as feasible: * The study protocol (will preferably be published in a journal; alternatively, it can be posted to https://osf.io/a5cdg/); * Participant information materials; * The paper form for the eCRF; * The data sharing plan.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne-Sophie GAMEZ, MD, PhD principal investigator
University Hospital, Montpellier
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sample in people with Asthma, run by University Hospital, Montpellier at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mepolizumab serum concentration (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.