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Study of Mepolizumab-based Regimen Compared to Conventional Therapeutic Strategy in Patients With Eosinophilic Granulomatosis With Polyangiitis (E-merge)

Study Purpose

The purpose of this study is to compare mepolizumab-based regimen to conventional therapeutic strategy for remission induction in patients with Eosinophilic Granulomatosis with Polyangiitis.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients with a diagnosis of EGPA independently of ANCA status, - Patients aged of 18 years or older, - Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥3, - Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤ 1 mg/kg/day (pulses of methylprednisolone before oral corticosteroid therapy are authorized) - Patients having given their written informed consent prior to participation in the study.
  • - Patients affiliated with social security or CMU (profit or being entitled)

    Exclusion Criteria:

    - Patients with GPA, MPA, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference, - Patients with vasculitis in remission of the disease defined as a BVAS <3.
  • - Patients with severe cardiac failure defined as class IV in New York Heart Association.
  • - Patients with acute infections or chronic active infections (including HIV, HBV or HCV and checked in the last 12 months), - Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment, - Pregnant women and lactation.
Patients with childbearing potential should have reliable contraception for the 12 months duration of the study,
  • - Patients with EGPA who have already been treated with mepolizumab within the previous 12 months, - Patients with hypersensitivity to a monoclonal antibody or biologic agent, - Patients with contraindication to use mepolizumab, cyclophosphamide, mesna, azathioprine or maintenance therapy used for vasculitis, - Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol, - Patients included in other investigational therapeutic study within the previous 3 months, - Patients suspected not to be observant to the proposed treatments, - Patients who have white blood cell count ≤4,000/mm3, - Patients who have platelet count ≤100,000/mm3, - Patients who have ALT or AST level greater that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease, - Patients unable to give written informed consent prior to participation in the study.
  • - Patients under tutorship or curatorship and protected adults.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05030155
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Assistance Publique - Hôpitaux de Paris
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Loic GUILLEVIN, MD, PhD
Principal Investigator Affiliation Assistance Publique - Hôpitaux de Paris
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOtherOther
Overall Status Not yet recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Eosinophilic Granulomatosis With Polyangiitis
Additional Details

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a rare systemic small-vessel vasculitis, associated with asthma and blood and tissue eosinophilia. EGPA belongs to the group of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), and commonly involves upper and lower respiratory tracts, the lungs, the peripheral nerve and the heart. Therapeutic management is based on glucocorticoids alone or in combination with conventional immunosuppressive agents, mainly azathioprine, methotrexate or cyclophosphamide, according to disease severity assessed by the Five Factor Score. Such treatments, in addition to their common side effects, are frequently insufficiently effective to control chronic asthma and/or rhinosinusitis, requiring long-term high-dose corticosteroids. Because EGPA shares common pathophysiological features with eosinophilic disorders and asthma, new therapeutic options used in these conditions could be of interest, in particular mepolizumab, a monoclonal anti-interleukin (IL)-5 antibody, which has shown promising results in two small preliminary studies to control disease activity and decrease glucocorticoids in cortico-dependant patients. In addition, mepolizumab has been recently evaluated in a prospective trial, the MIRRA trial, targeting a small niche of patients, i.e. those with corticodependent asthma unable to achieve disease control with low dose of glucocorticoids. Results published revealed that mepolizumab led to significantly more accrued weeks of remission than placebo (28% vs.#46; 3% of the participants had ≥24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs.#46; 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). However, these studies did not evaluate the interest of mepolizumab during EGPA flare associating asthma, eosinophilic and vasculitis lesions, in order to induce remission of the disease and rapidly decrease and discontinue glucocorticoids. Also, recent pathophysiological date strongly support in addition to previous therapeutic studies the major interest to target IL-5 as soon as EGPA is diagnosed: 1) genetic association studies demonstrated that polymorphisms in the IL-5 pathway are associated with EGPA in comparison with controls, 2) increased expression of IL-5 in mice model are able to induce vasculitis lesions as observed in the human diseases. Patients will receive a standardized glucocorticoid tapering schedule. From day 28 post-baseline onwards, if the subject's BVAS=0 their oral prednisone dose should be tapered downwards. A standardized glucocorticoid tapering schedule provided in the protocol enables a reduction in oral prednisone dose every 2 weeks, with the intention of achieving a prednisone dose of 4 mg/day or less. Once a subject has achieved a dose of 4 mg/day prednisone, the investigator is encouraged to continue tapering downwards, if clinically warranted, at dose increments of 1.0 mg every week. Upwards dose adjustments within the 0-4.0 mg range are permitted without necessarily being considered a relapse.

Arms & Interventions

Arms

Experimental: Patients with FFS=0 - Mepolizumab

Mepolizumab 300mg every 4 weeks until D336

Placebo Comparator: Patients with FFS=0 - Placebo

Placebo of Mepolizumab every 4 weeks until D336

Experimental: Patients with FFS≥1 - Mepolizumab

Mepolizumab 300mg every 4 weeks until D336 and placebo of Azathioprine 1mg/kg/day from D126 until D360 and placebo of cyclophosphamide/mesna at D1, D15, D28, D56, D84 and D112

Placebo Comparator: Patients with FFS≥1 - Placebo

Placebo of Mepolizumab every 4 weeks until D336, cyclophosphamide and mesna at D1, D15, D28, D56, D84 and D112 and Azathioprine 1mg/kg/day from D126 until D360

Interventions

Drug: - Mepolizumab

300 mg/month subcutaneous

Drug: - cyclophosphamide/azathioprine

Patients with FFS≥1 will receive cyclophosphamide then azathioprine

Drug: - Placebo

Patients with FFS=0 will receive placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Paris, France

Status

Address

Service de Médecine Interne, Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques "Hôpital Cochin

Paris, , 75014

Site Contact

Benjamin TERRIER, MD, PhD

benjamin.terrier@aphp.fr

(+33)1 58 41 14 61