Rituximab Vasculitis Maintenance Study

Completed · Phase 3

Conditions studied: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis, Wegener Granulomatosis

In brief

Rituximab is now established as an effective drug for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis following major European and US trials reported in 2010. After a time, its effect wears off and the disease can return. This occurs in at least half of patients within 2 years of receiving Rituximab. A preliminary study in Cambridge has suggested that repeating rituximab every six months stops the disease returning and is safe. The RITAZAREM trial will find out whether repeating rituximab stops vasculitis returning and whether it works better than the older treatments, azathioprine or methotrexate. It will also tell us how long patients remain well after the repeated rituximab treatments are stopped, and if repeated rituximab is safe. We should also learn useful information about the effects of rituximab on quality of life and economic measures. The trial results will help decide the best treatment for future patients who have their vasculitis initially treated with rituximab. RITAZAREM aims to recruit patients with established ANCA vasculitis whose disease has come back 'relapsing vasculitis'. All patients will be treated with rituximab and steroids and we anticipate that most will respond well. If their disease is under reasonable control after four months, further treatment with either rituximab (a single dose ever four months for two years) or azathioprine tablets will be chosen randomly. The patients in the rituximab and azathioprine groups will then be compared. Patients will be in the trial for four years. The study has been designed by members of the European Vasculitis Study group (EUVAS) and the Vasculitis Clinical Research Consortium (VCRC). It will include 190 participants from 30 hospitals in Europe, the USA, Australia and Mexico. RITAZAREM is being funded by Arthritis Research UK, the U.S. National Institutes of Health and by Roche/Genentech.

Key facts

Study ID: NCT01697267
Run by: Cambridge University Hospitals NHS Foundation Trust
People needed: 188
Starts: 2013-04-01
Expected to finish: 2019-11-21
Last updated by the study team: 2022-03-18

Who can join

Age: 15 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
Current or historical PR3/MPO ANCA positivity by ELISA
Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegeners (BVAS/WG), in patients that have previously achieved remission following at least 3 months of induction therapy, with a combination of glucocorticoids and an immunosuppressive agent (cyclophosphamide or methotrexate or rituximab or mycophenolate mofetil)
Written informed consent

You may not qualify if…

Age < 15 years (age < 18 years at centres that do not treat paediatric patients)
Exclusions related to medication:
Previous therapy with:
Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months
Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months
IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months
Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer)
Exclusions related to general health:
Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation
Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis,
Any concomitant condition anticipated to likely require greater than 4 weeks per year of oral or systemic glucocorticoid use and which would preclude compliance with the glucocorticoid protocol (e.g. poorly-controlled asthma, COPD, psoriasis, or inflammatory bowel disease).
History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies
Known infection with HIV (HIV testing will not be a requirement for trial entry); a past or current history of hepatitis B virus or hepatitis C virus infection.
Ongoing or recent (last 12 months) evidence of active tuberculosis or known active infection (screening for tuberculosis is part of "standard of care" in patients with established AAV) or evidence of untreated latent tuberculosis. Screening for tuberculosis is as per local practice.
History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure.
Pregnancy or inadequate contraception in pre-menopausal women
Breast feeding or lactating
Exclusion criteria related to laboratory parameters:
Bone marrow suppression as evidenced by a total white count < 4 x109/l, haemoglobin < 7 gm/dl or platelet count < 100,000/μl
Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis

Where it is running

Cedars-Sinai Medical Center — Los Angeles, California, United States
University of Michigan — Ann Arbor, Michigan, United States
Mayo Clinic — Rochester, Minnesota, United States
Hospital for Special Surgery — New York, New York, United States
University of North Carolina — Chapel Hill, North Carolina, United States
Cleveland Clinic — Cleveland, Ohio, United States
University of Pennsylvania — Philadelphia, Pennsylvania, United States
University of Pittsburgh — Pittsburgh, Pennsylvania, United States
University of Utah — Salt Lake City, Utah, United States
Canberra Hospital — Garran, Australian Capital Territory, Australia
Royal Brisbane & Women's Hospital — Herston, Queensland, Australia
Royal Adelaide Hospital — Adelaide, South Australia, Australia
St. Joseph's Healthcare — Hamilton, Ontario, Canada
Mount Sinai Hospital — Toronto, Ontario, Canada
General Faculty Hospital — Prague, Czechia
Cork University Hospital — Cork, Ireland
University Hospital of Parma — Parma, Italy
Okayama University — Kita-ku, Okayama-ken, Japan
Chiba University — Chiba, Japan
Kitano Hospital — Kyoto, Japan
University of Miyazaki — Miyazaki, Japan
Teikyo University — Tokyo, Japan
Tokyo Metropolitan Geriatric — Tokyo, Japan
Kyorin University school of medicine — Tokyo, Japan
Auckland City Hospital — Grafton, Auckland, New Zealand

Full record on ClinicalTrials.gov

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