Comparison of a Strategy Based on Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment in Cases of ANCA Reappearance in Granulomatosis With Polyangiitis and Microscopic Polyangiitis. (PREP-ANCA)

Comparison of Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment for ANCA Repositivation in Granulomatosis With Polyangiitis and Microscopic Polyangiitis: a Prospective, Multicenter, Randomized Controlled Study.

The PREP-ANCA study seeks to establish a more personalized treatment strategy for ANCA-associated vasculitides by assessing the efficacy of pre-emptive rituximab administration upon ANCA repositivity in preventing relapses in granulomatosis with polyangiitis and microscopic polyangiitis.

Study Overview

• Status: Not yet recruiting
• Conditions: Microscopic Polyangiitis (MPA); ANCA Associated Vasculitis (AAV); Polyangiitis (GPA)
• Intervention / Treatment: Drug: Rituximab

Detailed Description

Treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) is currently based on an induction phase aimed at achieving remission, followed by a maintenance phase to prevent relapse. Rituximab is considered a cornerstone of maintenance therapy, typically administered for a minimum of 18 months. However, the extension of rituximab treatment beyond this period remains debated, primarily due to the increased risk of infections associated with prolonged immunosuppression.

The use of biomarkers to guide treatment duration-extending therapy only in patients at high risk of relapse-represents a promising step toward personalized management. Among the potential biomarkers, ANCA (anti-neutrophil cytoplasmic antibodies) have emerged as a particularly attractive candidate, having been identified as an early marker of relapse. Early studies on pre-emptive immunosuppressive strategies have suggested that timely intervention could reduce relapse rates; however, none of these studies were conducted in the rituximab era. As a result, in the absence of a dedicated prospective randomized trial, current recommendations advise close monitoring in the event of isolated ANCA repositivity in patients who remain in clinical remission.

The objective of this study is to determine whether pre-emptive rituximab administration upon ANCA repositivity is superior to current standard care in reducing the risk of relapse.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Adèle BELLINO; Phone Number: +33 01 58 41 11 95; Email: adele.bellino@aphp.fr
• Study Contact Backup: Name: Florence DELESTRE, MD; Phone Number: +33 01 58 41 41 17; Email: florence.delestre@aphp.fr

Study Locations

• France
  • Paris, France, 75014
    • Hôpital Cochin
    • Contact: Benjamin TERRIER, PhD; Phone Number: +33 01 58 41 14 61; Email: benjamin.terrier@aphp.fr
    • Contact: Florence DELESTRE, MD; Phone Number: +33 01 58 41 41 27; Email: florence.delestre@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients aged ≥ 18 years
• Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria
• Maintenance treatment with rituximab for at least 18 months, administered as follows: a 500 mg infusion on day 1 (with an optional repeat dose on day 15), followed by 500 mg infusions every 6 months for a total of 4 to 5 doses
• Patient in complete remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 at the time of randomization
• ANCA repositivity (confirmed by antigen-specific testing) within the 3 months prior to randomization
• Ability to provide written informed consent prior to participation
• Affiliation to a national health insurance or social security scheme

Exclusion Criteria:

• Diagnosis of any vasculitis other than GPA or MPA
• Active disease relapse, defined as BVAS > 0
• Acute active infection requiring hospitalization or intravenous anti-infective therapy within 4 weeks prior to screening, or oral anti-infective treatment within 2 weeks prior to screening
• History of deep tissue infections (e.g., fasciitis, abscess, osteomyelitis, septic arthritis) within 12 months prior to inclusion
• History of severe, chronic, or recurrent infections, or any underlying condition predisposing the patient to serious infections
• Administration of a live vaccine within 4 weeks prior to study inclusion
• Active malignancy or history of hematologic malignancy within the past 5 years, except for localized prostate cancer or basal cell carcinoma of the skin
• Presence of systemic diseases for which the study treatments may have unpredictable or inappropriate consequences
• History of severe allergic or anaphylactic reactions, or known hypersensitivity to humanized or murine monoclonal antibodies and/or corticosteroids
• Known hypersensitivity to any monoclonal antibody or biologic agent
• Patients previously deemed non-responders or failures to rituximab therapy
• Suspicion of poor adherence to treatment or anticipated inability or refusal to comply with the required follow-up visits and procedures
• Inability or refusal to provide written informed consent Pregnant or breastfeeding women. Women of childbearing potential must use effective contraception during the study and for 6 months after the last infusion. Breastfeeding is contraindicated during treatment and for 6 months following the final rituximab dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab; Rituximab 500 mg administered intravenously (IV) every 6 months for a total duration of 18 months, depending on ANCA positivity.	Drug: Rituximab; 500 mg IV every 6 months for a total duration of 18 months depending on ANCA positivity.; Other Names: Mabthera; Rixathon; Tuxima
No Intervention: Control; Standard care follow up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival without relapse in each arm at 24 months. (relapse defined by The Birmingham Vasculitis Activity Score (BVAS) score > 0)	The BVAS is the most effective validated tool for documenting disease activity. It provides valid definitions of remission and response to treatment, as well as suggestions.	24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events		48 months
Number of participants with a major or a minor relapse during the study.		48 months
Number of serious adverse events such as potentially fatal, requiring hospitalisation, causing significant disability or resulting in death		48 months
Numbers of rituximab perfusions performed in each arms.		48 months
The index of damage caused by vasculitis according to the Vasculitis Damage Index (VDI)classification during follow-up	The Vasculitis Damage Index (VDI) comprises 64 items of damage (grouped into 11 organ-based systems) that a group of experts agreed was representative of the forms of damage incurred by patients with systemic vasculitis .	48 months
Quality of life according to Health Assessment Questionnaire (HAQ ) classifications during follow-up	HAQ (Health Assessment Questionnaire) is a functional disability tool specific to rheumatoid arthritis. The assessment covers the past week and 8 domains of physical activity. For each area of activity, 2 to 3 items are described. Each item can be modified with aids. Only items with a specified response or aid are taken into account. Scores range from 0 (no impact) to 3 (maximum impact).	48 months
Quality of life according to SF-36 classifications during follow-up	To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36 (v2) scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.	48 months
Mortality in each arm		48 months
Cumulative dose and duration of corticosteroid treatment in each arm		48 months
Evolution of ANCA levels and CD19+ B-lymphocyte in each study arm and their correlation with clinical events		48 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Chair: Benjamin TERRIER, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Rituximab; Granulomatosis with polyangiitis; ANCA; Microscopic polyangiitis
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Skin Diseases; Skin Diseases, Vascular; Lung Diseases, Interstitial; Vasculitis; Cerebral Small Vessel Diseases; Skin and Connective Tissue Diseases; Granulomatosis with Polyangiitis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab
• Other Study ID Numbers: APHP240796; 2025-522049-23-00 (Ctis)

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