Comparison Between a Long Term and a Conventional Maintenance Treatment With Rituximab

NCT02433522 | Completed Phase 3

• 2 other identifiers: P110146 extended2012-001963-66
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

MAINRITSAN study compared Rituximab and azathioprine as maintenance therapy for ANCA-associated vasculitides. In this study, Rituximab (5 infusions at D1, D15, M6, M12, M18) was superior to azathioprine (2 mg/kg/day) to prevent relapses of AAV 28 months after the inclusion (Guillevin et al. NEJM 2014). Nevertheless, in the follow-up study of MAINRITSAN, up to 30% of patients experienced a relapse 38 months after the last rituximab infusion (unpublished data). Right now, no randomized controlled study has been carried in order to evaluate the best duration of the maintenance treatment with rituximab. The investigators objective is to evaluate the efficacy of a long term rituximab treatment to prevent relapses of ANCA-associated vasculitis in patients in remission after a first phase of rituximab maintenance treatment. The investigators will conduct a randomized placebo-controlled trial of a long term rituximab maintenance treatment (46 months) against a conventional maintenance treatment (18 months).

Conditions

ANCA-associated Vasculitides

Keywords

ANCA-associated vasculitides; Maintenance treatment; Rituximab; Granulomatosis with polyangiitis; Microscopic polyangiitis

Outcome Measures

Primary Outcomes (1)

• Vasculitis score 2003 (BVAS 2003 )

  Relapse free survival rates (BVAS \> 0)

  28 months

Secondary Outcomes (17)

• Number of adverse events,

  28 months

• number of patients experiencing at least one adverse event in both arms

  28 months

• correlation of ANCA level with the clinical events

  28 months

• ANCA level during follow-up

  28 months

• correlation B-Lymphocytes CD-19 level with the clinical events

  28 months

Study Arms (2)

Rituximab

EXPERIMENTAL

500 mg rituximab infusion at the randomization visit and every 6 months for 18 months

Drug: rituximab

Placebo

PLACEBO COMPARATOR

Placebo infusion at the randomization visit and every 6 months for 18 months

Drug: Placebo

Interventions

rituximab DRUG

500 mg rituximab infusion at the randomization visit and every 6 months for 18 months. Each infusion will be preceded by an infusion of 1000 mg paracetamol, 100 mg methylprednisolone and 5 mg dexchlorpheniramine.

Rituximab

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Granulomatosis with Polyangiitis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission.
• Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins, or rituximab).
• Interval of 1 month between the end of the immunosuppressant treatment and the randomization time if cyclophosphamide or methotrexate were used, interval between 4 and 6 months if rituximab was used
• Age \> 18 years without age limit higher when the diagnosis is confirmed.
• Informed and having signed the consent form to take part in the study.
• and Patients must meet all of the following criteria:
• In complete remission (BVAS 0) at 28 months of MAINRITSAN2 study.
• Informed patient who accepted to participate in MAINRITSAN 2 and who signed the informed consent to this extension.
• Randomized on the day of the evaluation of the primary endpoint of MAINRITSAN 2 during the visit M28 (last visit of the protocol).

You may not qualify if:

• Eosinophilic granulomatosis with polyangiitis (EGPA)
• History of severe allergic manifestations or anaphylactic manifestations following humanized or murine monoclonal antibodies infusions
• Pregnant or breast feeding women. Contraception is required for women who could be pregnant during treatment follow up and during the year following the last infusion.
• Infection by HIV (positive serology), HCV (positive serology), or HBV (HBsAg positive or anti-HBc antibody positive with anti-HBs antibody negative)
• Other severe bacterial, viral , mycobacterial or fungal infection(s), occurring within the last 3 months before of randomization. A severe infection is defined by the hospitalization, a life or organ threatening.
• Severe chronic obstructive bronchopathy (FEV \< 50% or dyspnea stage III).
• Cardiac failure, stage IV according to the NYHA classification.
• Recent history of coronary artery disease (\<1 month).
• Patient with severe immunodepression characterized by clinical manifestations.
• Participation to another concomitant therapeutic study (except observational studies or studies without therapeutic intervention).
• Psychiatric disease that may interfere with the study.
• Non affiliation to a health insurance.
• Uncontrolled severe cardiac disease.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Roche Pharma AG: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hopital cochin

Paris, 75014, France

Location

Related Publications (2)

• Pagnoux C, Guillevin L; French Vasculitis Study Group; MAINRITSAN investigators. Rituximab or azathioprine maintenance in ANCA-associated vasculitis. N Engl J Med. 2015 Jan 22;372(4):386-7. doi: 10.1056/NEJMc1414728. No abstract available.

  PMID: 25607433 BACKGROUND

• Charles P, Perrodeau E, Samson M, Bonnotte B, Neel A, Agard C, Huart A, Karras A, Lifermann F, Godmer P, Cohen P, Hanrotel-Saliou C, Martin-Silva N, Pugnet G, Maurier F, Sibilia J, Carron PL, Gobert P, Meaux-Ruault N, Le Gallou T, Vinzio S, Viallard JF, Hachulla E, Vinter C, Puechal X, Terrier B, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med. 2020 Aug 4;173(3):179-187. doi: 10.7326/M19-3827. Epub 2020 Jun 2.

  PMID: 32479166 RESULT

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Loic GUILLEVIN, MD-PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: May 5, 2015
• Study Start: March 31, 2015
• Primary Completion: August 16, 2018
• Study Completion: August 16, 2018
• Last Updated: November 20, 2025

Record last verified: 2025-10

Locations

FR (1)