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

Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients with Newly-Diagnosed or Relapsing IgA Vasculitis: a Prospective, Randomized, Controlled, Double-blind Study

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 Overview

• Status: Active, not recruiting
• Conditions: IgA Vasculitis
• Intervention / Treatment: Drug: Rituximab Injection; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France, 29200
    • Hôpital La Cavale Blanche
  • Clermont-Ferrand, France, 63000
    • Chu Clermont Ferrand
  • Clermont-Ferrand, France, 63003
    • Chu Clermont Ferrand
  • Lyon, France, 69003
    • Hôpital Edouard Herriot
  • Marseille, France, 13005
    • CHU Marseille
  • Marseille, France, 13385
    • APHM de La Timone
  • Montreuil, France, 93100
    • Hôpital André Grégoire
  • Nantes, France, 44093
    • CHU Nantes
  • Nîmes, France, 30029
    • CHU Nîmes (Caremeau)
  • Paris, France, 75679
    • Hopital Cochin
  • Strasbourg, France, 67091
    • CHU Strasbourg
  • Suresnes, France, 92150
    • Hopital Foch
  • Toulouse, France, 31059
    • CHU Toulouse
  • Tours, France, 37044
    • CHRU Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; Experimental therapeutic strategy based on the use of rituximab in combination with glucocorticoids	Drug: Rituximab Injection; anti-CD20 monoclonal antibody leading to B-cell depletion, in relapsing and/or refractory IgAV patients; Other Names: Truxima; Rixathon
Placebo Comparator: control group; Control therapeutic strategy based on glucocorticoids plus placebo	Drug: placebo; placebo experimental treatment; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rituximab efficacy	The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 180 days	180 days
Rituximab efficacy	The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 360 days	360 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	360 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 180 days	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	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.	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)	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)	360 days
Measure of glucocorticoids dose	Area under the curve for prednisone dose at 180 days in the two treatment groups	160 days
Measure of glucocorticoids dose	Area under the curve for prednisone dose at 360 days in the two treatment groups	360 days
The sequelae assessed by the Vasculitis Damage Index	The Vasculitis Damage Index in the two treatment groups	180 days
The sequelae assessed by the Vasculitis Damage Index	The Vasculitis Damage Index in the two treatment groups	360 days
Quality of life of patients	HAQ and SF-36 questionnaires at 180 days	180 days
Quality of life of patients	HAQ and SF-36 questionnaires at 360 days	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	360 days
Patient survival	Number of patient survival	360 days

Collaborators and Investigators

• Sponsor: Hopital Foch
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Romain Paule, Dr, Hopital Foch

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Estimated): July 16, 2025
• Study Completion (Estimated): January 16, 2026

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Rituximab
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Immune System Diseases; Hemorrhage; Skin Manifestations; Hypersensitivity; Hematologic Diseases; Skin Diseases; Blood Coagulation Disorders; Skin Diseases, Vascular; Hemostatic Disorders; Hemorrhagic Disorders; Purpura; Immune Complex Diseases; Vasculitis; IgA Vasculitis; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Rituximab
• Other Study ID Numbers: 2019_0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No