Brief Title
Study of Mepolizumab-based Regimen Compared to Conventional Therapeutic Strategy in Patients With Eosinophilic Granulomatosis With Polyangiitis (E-merge)
Official Title
Evaluation of MEpolizumab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Eosinophilic Granulomatosis With Polyangiitis. Prospective, Randomized, Controlled, Double-blind Study
Brief Summary
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.
Detailed Description
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. 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. 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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Percentage of patients who achieved a prednisone dose of 4.0 mg or less per day at day 168, without experiencing a relapse
Secondary Outcome
Prednisone dosage at days 168 and 364
Condition
Eosinophilic Granulomatosis With Polyangiitis
Intervention
Mepolizumab
Study Arms / Comparison Groups
Patients with FFS=0 - Mepolizumab
Description: Mepolizumab 300mg every 4 weeks until D336
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
May 30, 2022
Completion Date
May 2025
Primary Completion Date
May 2025
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Loic GUILLEVIN, MD, PhD, (+33)1 58 41 14 61, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT05030155
Organization ID
D20180135
Secondary IDs
2020-003318-10
Responsible Party
Sponsor
Study Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
French Vasculitis Study Group
Study Sponsor
Loic GUILLEVIN, MD, PhD, Study Director, Assistance Publique - Hôpitaux de Paris
Verification Date
June 2022