Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. Prospective, randomized, controlled, double-blind study. - REOVAS

• Register: EUCTR
• Last refreshed on: 30 November 2020
• Main ID: EUCTR2016-000275-25-FR
• Date of registration: 13/04/2016
• Prospective Registration: No
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
• Public title: Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. Prospective, randomized, controlled, double-blind study. - REOVAS
• Scientific title: Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. Prospective, randomized, controlled, double-blind study. - REOVAS
• Date of first enrolment: 21/03/2016
• Target sample size: 108
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000275-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCD Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

• Name: DRCD Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients with a diagnosis of EGPA independently of ANCA status,
- Patient 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) > ou=3,
- Patients within the first 21 days following initiation/increase of corticosteroids at a dose - Patient able to give written informed consent prior to participation in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Patients with GPA, MPA, or other vasculitides, 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 Assocation
- Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
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 all duration of the study,
- 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 with EGPA who have already been treated with rituximab within the previous 12 months,
- Patients with hypersensitivity to a monoclonal antibody or biologic agent,
- Patients with contraindication to use rituximab or cyclophosphamide,(only patients DFS< ou=1)
- 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 < ou=4,000/mm3,
- Patients who have platelet count < ou =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.

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Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with a diagnosis of EGPA with newly-diagnosed disease or with a relapsing disease at the time of screening
MedDRA version: 19.0 Level: PT Classification code 10048594 Term: Allergic granulomatous angiitis System Organ Class: 10021428 - Immune system disorders

Intervention(s)

Trade Name: RITUXIMAB
Product Name: RITUXIMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
Other descriptive name: RITUXIMAB
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 10mg/ml-
Pharmaceutical form of the placebo: Concentrate for solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: CYCLOPHOSPHAMIDE
Product Name: CYCLOPHOSPHAMIDE
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: MESNA
Product Name: MESNA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: mesna
Other descriptive name: MESNA
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 100mg/ml-
Pharmaceutical form of the placebo: Concentrate for solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The percentage of patients who obtained a BVAS=0 at day 180.
Remission will be defined as the absence of disease activity attributable to EGPA vasculitis manifestations (parenchymal lung disease, peripheral nerve involvement, skin, cardiac, renal and/or gastrointestinal signs), corresponding to BVAS=0, with a prednisone dose < ou =7.5 mg/day.
Secondary assessment criteria
- The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 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 (within 24 hours of infusion) that result in the cessation of further infusions
- The area under the curve for corticosteroids at at days 180 and 360 day 180 and day 360 in the two treatment groups
- The Vasculitis Damage Index at days 180 and 360 at day 180 and day 360 in the two treatment groups
- The HAQ and SF-36 at days 180 and 360 at day 180 and day 360 in the two treatment groups
- Evolution of ANCA titers and CD19+ cells in the two treatment groups, and correlation with clinical events

Secondary Objective: - To compare the safety profile of rituximab and conventional treatment at days 180 and 360
- To measure the corticosteroid dose at days 180 and 360 and to compare the corticosteroid sparing effect of rituximab versus conventional therapy
- To compare sequelae assessed by the Vasculitis Damage Index at days 180 and 360 in both arms
- To compare functional disability and quality of life at 180 days after randomization in both arms
- To compare the evolution of ANCA titers and CD19+ cells in the two treatment groups, and to assess its correlation with clinical events

Main Objective: To determine the efficacy of rituximab and glucocorticoids to induce a complete remission, defined as a Birminghman Vasculitis Activity Score (BVAS) of 0 and a prednisone dose < ou =7.5 mg/day at day 180, in patients with newly-diagnosed or relapsing EGPA.

Secondary ID(s)

P140915

Source(s) of Monetary Support

DGOS

Ethics review

Status: Approved
Approval date: 16/02/2016
Contact: