Patients with a diagnosis of IgAV according to Chapel Hill Consensus Conference definitions. Patients will require having a biopsy-proven diagnosis of IgAV.
Conditions
Interventions
Trade Name: RituxiMab (MabThera)
Product Name: RituxiMab
Pharmaceutical Form: Injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: monoclonal antibody
Pharmaceutica
Sponsors
Hôpital Foch
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Biopsy-proven diagnosis of IgAV according to Chapel Hill Consensus Conference definitions, 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 by active manifestations attributable to IgAV Patients with severe involvement of at least one organ: o Patients with biopsy-proven IgA-related nephritis class 3 or 4 (i.e. MEST-C score E1C0, E1C1 or C2) o Patients with acute renal failure with eGFR 1 g/g. o Gastrointestinal involvement defined as intestinal hemorrhage, ischemia, perforation, and/or abdominal pain unresponsive to common analgesics and lasting for >24 hours; o Pulmonary hemorrhage; o Ocular involvement with scleritis; o Cardiac involvement; o Peripheral and/or central nervous system involvement o Extensive necrotizing cutaneous involvement. Patients within the first 21 days following initiation/increase of glucocorticoids at a dose =1 mg/kg/day (pulses of methylprednisolone before oral glucocorticoids therapy are authorized) Patients must have signed an informed consent form prior to any study related procedures Patients must be affiliated to the national health insurance 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: Patients with ANCA-associated vasculitis, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference, Patients with IgAV in remission of the disease, 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), Patients with active cancer or recent malignancy (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment, Pregnant women and breastfeeding. Patients with childbearing potential must use reliable contraceptive methods throughout the study and at least for 12 months after the last study drug administration, Patients with IgAV who have already been treated with rituximab within the previous 12 months, Patients treated with immunosuppressive therapy within the last 3 months, Patients with hypersensitivity to human or chimeric monoclonal antibodies, Patients with contraindication to use rituximab, Patients treated with any concomitant drugs contraindicated for use with the rituximab according to its SmPC, Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to the protocol requirements, Patients currently participating in another clinical study or 3 months prior to randomization, Patients suspected not to be observant to the proposed treatments, Patients unable to give written informed consent prior to participation in the study, Being deprived of liberty or under guardianship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of rituximab to induce remission in patients with newly-diagnosed or relapsing adult IgAV;Secondary Objective: To determine the duration of efficacy of rituximab-based regimen to induce remission in studied patients To assess the number of relapses To compare the safety profile of rituximab-based regimen and glucocorticoids alone at days 180 and 360 To measure the glucocorticoids dose at days 180 and 360 and to compare the glucocorticoid sparing effect of rituximab To assess the proportion of patients in complete or partial renal remission at days 180 and 360. To assess renal outcome To compare sequelae assessed by the Vasculitis Damage Index at days 180 and 360 in both arms To compare patient-reported outcomes (PRO) at days 180 and 360 after randomization in both arms, and during long-term follow-up. To compare functional disability and quality of life at days 180 and 360 after randomization in both arms To compare the evolution of CD19+ cells in the two treatment groups, and to assess its correlation with clinical events during follow-up ;Primary end point(s): The proportion of patients alive who achieve remission with a prednisone dose of 0 mg/day at both days 180 and 360. Remission will be defined as the absence of disease activity attributable to active IgAV assessed using the Birmingham Vasculitis Activity Score (BVAS) and a prednisone dose of 0 mg/day. Absence of disease activity attributable to active IgAV corresponds to: -BVAS =0 in the absence of renal involvement; -BVAS =5 if all scores were due to persistent hematuria or proteinuria in the presence of stable or improving renal function. In patients with renal involvement related to IgAV, presenting with hematuria and/or proteinuria, we decided to define remission differently than in those without renal involvement since hematuria and/or proteinuria can persist for a long time independently of disease activity ;Timepoint(s) of evaluation of this end point: D3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients in remission at days 180 Proportion of patients in remission at days 360 Proportion of patients in remission both at days 180 and 360 Proportion of patients achieving remission for =3 consecutive months over the 360 days study period Proportion of patients with BVAS=0 (or BVAS of =5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose =5 mg/day at days 180 and 360 Mean total accrued duration in weeks in remission of the disease (as previously defined) over the 360 days study period Proportion of patients in complete renal and partial renal remission at days 180 and 360. Renal parameters at days 180 and 360 compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease Prednisone dosage at days 180 and 360 in the two treatment groups Area under the curve for prednisone dose at days 180 and 360 in the two treatment groups Number of major and minor relapse at 12 months Cumulative incidence of relapse at 12 months Time to first IgAV relapse 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, 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, death The Vasculitis Damage Index at days 180 and 360 in the two treatment groups Quality of life as measured by the HAQ and SF-36 questionnaires at days 180 and 360. The patient-reported outcomes (PRO) including patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at days 180 | — |
Countries
France
Contacts
Public ContactDRCI
Hôpital Foch
Outcome results
None listed