Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis

NCT03920722 | Completed Phase 3 DMC

• 2 other identifiers: P170909J2018-000637-12
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine wether a rituximab-based treatment compared to standard therapy (glucocorticoid alone) in patients with microscopic polyangiitis without any bad prognosis marker increases the remission and reduces the relapse free survival rate.

Conditions

Microscopic Polyangiitis (MPA)

Keywords

MPA; Rituximab; ANCA-associated vasculitis

Outcome Measures

Primary Outcomes (1)

• Disease free survival rate

  Failure free survival in patients with microscopic polyangiitis treated with rituximab and glucocorticoids compared to glucocorticoids alone. * Primary failure: Vasculitis requiring a modification of immunosuppressive treatment or prednisone tapering protocol before M3 * Remission is defined by the absence of sign attributable to vasculitis and a Birmingham Vasculitis Activity Score (BVAS)=0 at M3 * Relapse is defined after visit M3 by a BVAS\>0 or the impossibility to decrease glucocorticoids according to the predefined protocol. Therefore, patients who experience a primary failure or fail to enter remission or relapse will be considered as treatment failure. Death will also be considered as a treatment failure

  18 months

Secondary Outcomes (12)

• Cumulative dose of GC in each group

  18 months

• Proportion of patients who achieve a complete remission defined by the absence of sign attributable to vasculitis and a BVAS=0

  1 month

• Compare proportion of patients who relapse and time to first relapse

  18 months

• Among patients who relapse, proportion of major relapses

  18 months

• Among patients who relapse, proportion of minor relapses

  18 months

Study Arms (2)

Rituximab

EXPERIMENTAL

Experimental regimen: One year Glucocorticoid treatment and Rituximab IV 1 gram on Day 1 and 15

Drug: Rituximab

Rituximab-Placebo

PLACEBO COMPARATOR

Standard regimen: One-year Glucocorticoid treatment and Placebo-Rituximab IV on Day 1 and 15

Drug: placebo

Interventions

Rituximab DRUG

1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine

Rituximab

placebo DRUG

Placebo-Rituximab 1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine

Rituximab-Placebo

Eligibility Criteria

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

You may qualify if:

• Patient (male or female) over 18 year old
• Patient agree to participate in the study and signed written informed consent
• Patient with MPA according to the CHCC established in 2012
• Absence of any poor prognosis factor (modified five factor score (FFS) 1996 = 0)
• Patient with recent onset or relapse of the disease (\<1 month) defined by BVAS \> 0, who did not received any other treatment than glucocorticoids during last month. For patients with a BVAS\<3, activity of vasculitis (either relapse or new onset) has to be confirmed by the coordinating investigator. One to 3 initial glucocorticoids pulse(s) are allowed.
• Patient with anti-MPO antibody measured by enzyme - linked immunosorbent assay (ELISA).
• Negative pregnancy test (serum β-hCG) for women of child-bearing potential and a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 12 months after stopping therapy

You may not qualify if:

• Small-sized vessels vasculitis not associated to anti-MPO antibody or associated with anti-PR3 positivity.
• Patients with either GPA or EGPA vasculitis according to ACR criteria
• Patient with a modified FFS 1996 ≥ 1
• Patient with alveolar hemorrhage requiring mechanical ventilation
• Patient with previous glucocorticoids treatment \>1 month and \> 10mg/day either for vasculitis or for any other reason.
• Patient already receiving immunosuppressant or biological agent.
• Prior treatment with any of the following:
• Patient with a previous diagnosis of cancer \< 5 years (except for in situ cervical cancer and skin carcinoma with R0 resection)
• Patient with acute infections or chronic active infections (HIV, hepatitis B or C)
• Breast feeding woman or woman refusing the use of a contraceptive method for the 18 months' duration of the study
• Contraindication to treatment (glucocorticoids or rituximab)
• Unable to receive written informed consent of patient. Patient unable to understand the protocol
• Patient already in another therapeutic protocol
• Patient without social security
• Patient with severe cardiac failure defined as class IV in New York Heart Association classification or severe, uncontrolled cardiac disease.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• French Vasculitis Study Group: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital

Paris, 75014, France

Location

Related Publications (5)

• Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Puechal X, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231.

  PMID: 25372085 BACKGROUND

• Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277.

  PMID: 23902481 BACKGROUND

• Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.

  PMID: 20647199 BACKGROUND

• Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169.

  PMID: 20647198 BACKGROUND

• Samson M, Puechal X, Devilliers H, Ribi C, Cohen P, Bienvenu B, Ruivard M, Terrier B, Pagnoux C, Mouthon L, Guillevin L; French Vasculitis Study Group (FVSG). Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors. Autoimmun Rev. 2014 Feb;13(2):197-205. doi: 10.1016/j.autrev.2013.10.001. Epub 2013 Oct 23.

  PMID: 24161361 BACKGROUND

MeSH Terms

Conditions

Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

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

• Luc Mouthon, MD PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: April 19, 2019
• Study Start: October 24, 2020
• Primary Completion: September 6, 2023
• Study Completion: September 6, 2023
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)