Evaluation of Glucocorticoids Plus Rituximab in Patients with Newly-Diagnosed or Relapsing IgA Vasculitis

Phase 3Active Not RecruitingNCT05329090

Hopital Foch75 enrolled

Overview

Systemic vasculitis are inflammatory diseases of the blood vessels, responsible for systemic manifestations. Among the systemic vasculitis affecting small blood vessels, IgA vasculitis (IgAV) is one of the most common forms and mainly affects the skin, joints, kidneys and gastrointestinal tract. Kidney and gastrointestinal damage can be serious, causing complications and life-threatening sequelae, especially in adults. The treatment of adult-onset IgAV is still a matter of debate. Glucocorticoids have been the standard of care for inducing remission for years in severe forms of IgAV. However, not all patients achieve remission and may experience disease flares associated with increased morbidity and mortality. In addition, the cumulative side effects of glucocorticoids are also major causes of long-term adverse events and death.Rituximab (RTX), an anti-CD20 monoclonal antibody, has been shown to be spectacularly effective in inducing remission in d 'other small vascular vessels, in particular ANCA-associated vasculitis and cryoglobulinemic vasculitis, with an acceptable safety profile. Recently, a multicenter observational study suggested that RTX was an effective and safe therapeutic option for treating relapsed and / or refractory adult IgAV. Overall, RTX may be an effective and safe therapeutic approach in adult IgAVs, justifying the need for a prospective randomized controlled trial evaluating Rituximab as an induction of remission for adult IgAV.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

IgA Vasculitis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 * Patients within the first 21 days following initiation/increase of glucocorticoids at a dose \< 1 mg/kg/day * Has signed an informed consent form prior to any study related procedures * Affiliated to a national health insurance 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 severe, uncontrolled cardiac disease, * 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 contraindication to use routine care treatments (Glucocorticoids, Angiotensin-converting-enzyme (ACEis) or angiotensin receptor blockers (ARBs), dexchlorphéniramine), * Patients in a severely immunocompromised state, * Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to 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.

Locations (14)

Hopital La Cavale Blanche

Brest, France

CHU Clermont Ferrand

Clermont-Ferrand, France

CHU Clermont Ferrand

Clermont-Ferrand, France

Hôpital Edouard Herriot

Lyon, France

CHU Marseille

Marseille, France

APHM de La Timone

Marseille, France

Hôpital André Grégoire

Montreuil, France

CHU Nantes

Nantes, France

CHU Nîmes (Caremeau)

Nîmes, France

Hôpital Cochin

Paris, France

...and 4 more locations

Outcomes

Primary Outcomes

Rituximab efficacy

The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 180 days

Time frame: 180 days

Rituximab efficacy

The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 360 days

Time frame: 360 days

Secondary Outcomes

Efficacy of rituximab-based regimen to induce remission

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 180 days

Time frame: 180 days

Efficacy of rituximab-based regimen to induce remission

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 360 days

Time frame: 360 days

Assessement the duration of remission

Proportion of patients achieving remission for ≥3 consecutive months over the 360 days, 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 360 days.

Time frame: 360 days

Assessment of patients achieving a complete or partial renal remission & renal outcome remission

Proportion of patients in complete renal and partial renal remission at 180 days (Renal parameters at 180 days compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease)

Time frame: 180 days

Assessment of patients achieving a complete or partial renal remission & renal outcome remission

Proportion of patients in complete renal and partial renal remission at 360 days (Renal parameters at 360 days compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease)

Time frame: 360 days

Measure of glucocorticoids dose

Area under the curve for prednisone dose at 180 days in the two treatment groups

Time frame: 160 days

Measure of glucocorticoids dose

Area under the curve for prednisone dose at 360 days in the two treatment groups

Time frame: 360 days

Number of participants with adverse events for the safety analyse

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

Time frame: 360 days

The sequelae assessed by the Vasculitis Damage Index

The Vasculitis Damage Index in the two treatment groups

Time frame: 180 days

The sequelae assessed by the Vasculitis Damage Index

The Vasculitis Damage Index in the two treatment groups

Time frame: 360 days

Quality of life of patients

HAQ and SF-36 questionnaires at 180 days

Time frame: 180 days

Quality of life of patients

HAQ and SF-36 questionnaires at 360 days

Time frame: 360 days

Patient reported outcome

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 and 360 after randomization in the two treatment groups, and during the long-term follow-up

Time frame: 360 days

Patient survival

Number of patient survival

Time frame: 360 days

Evaluation of Glucocorticoids Plus Rituximab in Patients with Newly-Diagnosed or Relapsing IgA Vasculitis

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes