Study of Magnitude and Prediction of Response to Omalizumab and Mepolizumab in Adult Severe Asthma.

Severe Asthma Clinical Trial

— PREDICTUMAB  

Official title:

Predictive Factors and Magnitude of Response to Omalizumab and Mepolizumab in Allergic and Eosinophilic Severe Asthma: a Pragmatic Multicenter Trial in Belgium.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03476109
• Other study ID #: 2017/19JUI/325
• Secondary ID: PNEU-ASTHMA-0220
• Status: Recruiting
• Phase: Phase 4
• Start date: May 10, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2022
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: Charles Pilette, MD PhD
• Phone: 003227642866
• Email: charles.pilette[@]uclouvain.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pragmatic trial to define the magnitude and the predictive factors of the response to omalizumab and mepolizumab in adult patients with severe refractory asthma and eligible to both therapies.

Description:

Title "PREDICTUMAB: Predictive factors and magnitude of response to omalizumab and mepolizumab in allergic and eosinophilic severe asthma: a multicenter, open, active-controlled, randomized trial in adult patients in Belgium".

Rationale and background New treatments are now available to treat severe refractory asthma, which affects about 3 to 5% of asthma patients. In particular, biological therapies using monoclonal antibodies targeted to immunoglobulin E (IgE) or interleukin (IL)-5 (and in the future other cytokines or growth factors) benefit to certain patients. Identifying those patients who will better benefit from a specific treatment requires the validation of features (clinical traits, biomarkers) that are predictive of the therapeutic outcome. Such predictive strategy is not available to decide whether anti-IgE (omalizumab) or anti-IL-5 (mepolizumab) should be prioritized in patients who are eligible to both therapies. In addition, the comparison of the magnitude of the clinical benefits achieved by these therapies remains unexplored in this population.

Study Design

The study is designed to initially randomly allocate patients from two strata (with or without maintenance oral corticosteroids) to oma- vs mepolizumab. According to the evaluation of response (at 4 or 6 months, respectively), subjects will then be either prolonged (for 12 months, for both therapies) on the same therapy, or switched to the other. For those who were switched, treatment will be prolonged (or not, in dual failers) after 4 or 6 months according to their evaluation of response. Time-points for analysis will be at 4 or 6 months, 10 months (interim analysis) and 18 or 22 months (final, posttreatment analysis).

State-of-the-art

Asthma is one of the most frequent chronic diseases, affecting 5 to 10% of the population worldwide. Omalizumab and mepolizumab represent the approved antibodies that are indicated in allergic and eosinophilic phenotypes of severe asthma respectively. However, if some patients fall into only one phenotypic category based on these criteria, a substantial number of patients are potentially eligible to both therapies. In those patients, no information is available to orientate towards a preferable therapy as the predictive weight of additional phenotypic traits, such as associated nasal polyps or early- versus late onset of disease, remains unknown. In addition, no head-to-head comparison of these therapies is available in this population.

Objectives of the study

Primary objectives To determine clinical features and blood (or sputum) biomarkers able to predict a better response to omalizumab or mepolizumab in severe asthma patients eligible to both therapies.

To determine the magnitude of response, in terms of improvement in symptoms, exacerbation rate and/or lung function, in responders to omalizumab vs mepolizumab.

Secondary objectives To compare the global baseline characteristics (clinical and biological features) of patients responding to omalizumab vs mepolizumab.

Management and reporting of adverse events.

If during the study, an adverse event (AE) (serious or non-serious) is identified as attributed to omalizumab or mepolizumab, this will be documented as appropriate in routine good clinical practice, to the Federal Agency of Medicines and Products of Health (AFMPS) as well as to the Central Ethic Committee.

Confidentiality of data.

The identity and participation of subjects will remain strictly confidential, according to Belgian laws dated 8 Dec 1992 related to the protection of private life and dated 22 Aug 2002 related to patient rights.

Specimens and associated data will be labeled with unique patient identification number.

Data will be anonymized in all files, results and publications related to the study.

The promoter confirms to authorize the regulatory surveillance, examination and controls by competent authorities, by allowing direct access to database/files, and this in full respect of confidentiality.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria: • Signed informed consent form (ICF),

• Age >18+ years at time of signing ICF,

• Able to comply with the study protocol, in the investigator's judgment,

• Documented physician-diagnosed asthma ,

• Patients with severe disease and eligible to omalizumab and mepolizumab, and who have not yet received any of these therapies.

Exclusion Criteria:

• History of evidence of drug/substance abuse that would pose a risk to patient safety, interfere with the conduct of study, have an impact on the study results, or affect the patient's ability to participate in the study, in the opinion of the investigator

• Treatment with any investigational therapy within 6 months or 5 drug half-lives prior to enrolment.

• Known sensitivity to any of the active substances or their excipients to be administered during the study.

Related Conditions & MeSH terms

• Asthma
• Severe Asthma

Intervention

Drug:
• Randomisation to omalizumab
The only intervention will be that allocation of patients to omalizumab or mepolizumab (to both of which patients will be eligible) will be randomized, to avoid that the initial decision is biased by confounding factors that are likely, but unproven, to affect the treatment response. Then, in case of non-response, patients will be switched to the other drug, as routine clinical practice would indicate.
• Randomisation to mepolizumab
The only intervention will be that allocation of patients to omalizumab or mepolizumab (to both of which patients will be eligible) will be randomized, to avoid that the initial decision is biased by confounding factors that are likely, but unproven, to affect the treatment response. Then, in case of non-response, patients will be switched to the other drug, as routine clinical practice would indicate.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussel	Brussels
Belgium	Cliniques universitaires St-Luc	Brussels
Belgium	Brugmann University Hospital	Bruxelles
Belgium	Centre Hospitalier Universitaire Saint Pierre	Bruxelles
Belgium	Erasme University Hospital	Bruxelles
Belgium	CHU de Charleroi	Charleroi	Hainaut
Belgium	Grand Hôpital de Charleroi	Charleroi	Hainaut
Belgium	University Hospital, Ghent	Gent
Belgium	Katholieke Universiteit Leuven	Leuven	Vlaams Brabant
Belgium	University Hospital of Liege	Liège
Belgium	Centre Hospitalier Universitaire Dinant Godinne - UCL Namur	Namur
Belgium	CHR Namur	Namur
Belgium	AZ Delta Roeselare	Roeselare	West-vlaanderen

Sponsors (12)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain	AZ Delta, Brugmann University Hospital, Centre Hospitalier Universitaire Dinant Godinne - UCL Namur, Centre Hospitalier Universitaire Saint Pierre, CHU de Charleroi, Erasme University Hospital, Grand Hôpital de Charleroi, KU Leuven, Universitair Ziekenhuis Brussel, University Hospital, Ghent, University of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy on asthma symptoms	Asthma Control Test: 5 items of score 1 to 5 about symptoms, with result of 20 or above indicates good control; 15 to 19 indicates no good control and below 15 indicates no control at all, and a change of 3 points considered as clinically significant.	Up to 22 months
Primary	Efficacy on lung function	Lung function measured as forced expiratory volume in one sec (FEV1), % predicted value (normal value of 80% predicted or above, and change of 100 mL considered as clinically significant).	Up to 22 months
Primary	Efficacy on severe exacerbations	Number of exacerbation(s) per period of time (corrected per year) requiring systemic corticosteroid treatment for at least 3 days, and/or emergency visit or hospitalization for acute asthma.	Up to 22 months
Secondary	Predictive factors of therapeutic response	The putative predictive factors of therapeutic response to omalizumab or mepolizumab which will be assayed are the following: age at onset, year (> or < 30yrs); presence of nasal polyps, Y/N; blood eosinophils, n/microliter (< or > 300/microl); serum total IgE, units/L; serum periostin, ng/ml. A proteomic analysis will also be carried out on plasma samples.	Baseline features (and according to response at 22 months)