Evaluation of MEpolizumab-based regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Eosinophilic Granulomatosis With Polyangiitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 May 2022 → 5 Sep 2025

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

GlaxoSmithKline · Ministry of Health - PHRC

External identifiers

EU CT number

2024-513653-75-00

EudraCT number

2020-003318-10

ClinicalTrials.gov

NCT05030155

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the glucocorticoid-sparing effect of mepolizumab-based regimen, defined as a prednisone dose of 4.0 mg or less per day at day 168, in patients with newly-diagnosed or relapsing EGPA

Secondary objectives 13

1. Measure glucocorticoid dose at D168&364 of mepolizumab vs conventional therapy; glucocorticoid cumulative dose at D168&364 of mepolizumab vs conventional therapy
2. To measure the glucocorticoid cumulative dose at days 168 and 364 of mepolizumab versus conventional therapy
3. To compare the proportions of participants who had a prednisone dose of 4.0 mg or less per day for 0 weeks, for more than 0 weeks but less than 4 weeks, for more than 4 weeks but less than 12 weeks, and for at least 12 weeks (categorical quantification).
4. To compare the proportion of participants who had a prednisone dose of 4.0 mg or less per day at both days 168 and 364.
5. To compare the proportion of participants experiencing a relapse.
6. To compare the number of relapse during the study period
7. To compare the number of asthma and sinonasal exacerbations during the study period in both arms
8. To compare the time from inclusion to first relapse.
9. To compare asthma control and sinonasal manifestations during the study period in both arms
10. To compare the safety profile of mepolizumab and conventional treatment at days 168 and 364.
11. To compare sequelae assessed by the Vasculitis Damage Index at days 168 and 364 in both arms.
12. To compare functional disability and quality of life at days 168 and 364 after randomization in both arms.
13. To compare the evolution of ANCA titers and eosinophils in the two treatment groups, and to assess its correlation with clinical events during follow-up.

Conditions and MedDRA coding

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with a diagnosis of EGPA independently of ANCA status
2. Patient aged of 18 years or older
3. 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
4. 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)
5. Written informed consent prior to participation in the study
6. Affiliation to social security or CMU (beneficiary or assignee)

Exclusion criteria 18

1. Patients with GPA, MPA, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference
2. Patients with vasculitis in remission of the disease defined as a BVAS <3
3. Patients with severe cardiac failure defined as class IV in New York Heart Association
4. Patients with acute infections or chronic active infections (including HIV, HBV or HCV and checked in the last 12 months)
5. Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment
6. Pregnant women and lactation. All women of childbearing potential (WOCBP) are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study and for WOCPB with FFS≥1 at least 12 months after stopping cyclophosphamide: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (Oral, Intravaginal, Transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (Oral, Injectable, Implantable); Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised Partner
7. Men with FFS≥1 who refuse to use effective method of contraception (condom) from the date of consent through the end of the study and at least 6 months after stopping cyclophosphamide (unless permanently sterile by bilateral orchidectomy)
8. Patients with EGPA who have already been treated with mepolizumab or benraluzimab within the previous 6 months
9. Patients with hypersensitivity to a monoclonal antibody or biologic agent
10. Patients with contraindication to use mepolizumab, cyclophosphamide, mesna, azathioprine or maintenance therapy used for vasculitis
11. 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
12. Patients included in other investigational therapeutic study within the previous 3 months
13. Patients suspected not to be observant to the proposed treatments
14. Patients who have white blood cell count ≤4,000/mm3
15. Patients who have platelet count ≤100,000/mm3
16. Patients who have ALT or AST level greater that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease
17. Patients unable to give written informed consent prior to participation in the study
18. Patients under tutorship or curatorship and protected adults

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percentage of patients who achieved a prednisone dose of 4.0 mg or less per day at day 168, without experiencing a relapse

Secondary endpoints 13

1. Prednisone dosage at days 168 and 364
2. The area under the curve for corticosteroids at days 168 and 364 in the two treatment groups
3. Proportion of participants with a prednisone dose of 4.0 mg or less per day for 0 weeks, for more than 0 weeks but less than 4 weeks, for more than 4 weeks but less than 12 weeks, and for at least 12 weeks (categorical quantification)
4. Proportion of participants with a prednisone dose of 4.0 mg or less per day at both days 168 and 364
5. Proportion of participants experiencing a relapse
6. Number of relapse during the study period
7. Number of asthma and sinonasal exacerbations during the study period
8. Time from inclusion to first relapse
9. The ACQ and SNOT-22 during the study period
10. The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 168 and 364 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorraghic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions that result in the cessation
11. The Vasculitis Damage Index at days 168 and 364 in the two treatment groups
12. The HAQ and SF-36 at days 168 and 364 in the two treatment groups
13. Evolution of ANCA titers and eosinophils in the two treatment groups, and correlation with clinical events during follow-up

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Benjamin TERRIER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Benjamin TERRIER

Locations

1 EU/EEA country · 54 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications