Rituximab Vasculitis Maintenance Study

• Register: ClinicalTrials.gov
• Last refreshed on: 25 January 2021
• Main ID: NCT01697267
• Date of registration: 31/08/2012
• Prospective Registration: Yes
• Primary sponsor: Cambridge University Hospitals NHS Foundation Trust
• Public title: Rituximab Vasculitis Maintenance Study RITAZAREM
• Scientific title: An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis
• Date of first enrolment: April 2013
• Target sample size: 188
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01697267
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Canada, Czech Republic, Czechia, Ireland, Italy, Japan, New Zealand, Sweden, United Kingdom, United States

Contacts

• Name: Peter Merkel
• Affiliation: University of Pennsylvania

• Name: David Jayne
• Affiliation: Cambridge University Hospitals NHS Foundation Trust

Key inclusion & exclusion criteria

Inclusion Criteria:

1. A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis],
according to the definitions of the Chapel Hill Consensus Conference

2. Current or historical PR3/MPO ANCA positivity by ELISA

3. 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)

4. Written informed consent

Exclusion Criteria:

1. Age < 15 years (age < 18 years at centres that do not treat paediatric patients)

2. Exclusions related to medication:

Previous therapy with:

1. Any biological B cell depleting agent (such as rituximab or belimumab) within the
past 6 months

2. Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months

3. IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3
months

4. Any investigational agent within 28 days of screening, or 5 half lives of the
investigational drug (whichever is longer)

3. Exclusions related to general health:

1. Significant or uncontrolled medical disease not related to AAV, which in the
investigators opinion would preclude patient participation

2. Presence of another multisystem autoimmune disease, including Churg Strauss
syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic
vasculitis,

3. 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).

4. History of severe allergic or anaphylactic reactions to humanised or murine
chimeric monoclonal antibodies

5. 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.

6. 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.

7. 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.

8. Pregnancy or inadequate contraception in pre-menopausal women

9. Breast feeding or lactating

4. Exclusion criteria related to laboratory parameters:

1. Bone marrow suppression as evidenced by a total white count < 4 x109/l,
haemoglobin < 7 gm/dl or platelet count < 100,000/µl

2. Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the
upper limit of normal, unless attributed to vasculitis



Age minimum: 15 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Microscopic Polyangiitis

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Wegener Granulomatosis

Intervention(s)

Biological: Rituximab

Drug: Azathioprine

Primary Outcome(s)

Time to relapse [Time Frame: Any patients who have not relapsed at up to a maximum of 4 years will be censored.]

Secondary Outcome(s)

Remission at 24 and 48 months [Time Frame: 24 and 48 months]

Combined damage assessment score [Time Frame: Assessed at months 0, 4, 12, 24, 36]

Infection rates [Time Frame: Up to 4 years]

Severe adverse event rate [Time Frame: Up to 4 years]

Cumulative GC exposure [Time Frame: Up to 4 years]

Health-related quality of life [Time Frame: Assessed at months 0, 4, 12, 24, 36]

Secondary ID(s)

2012-001102-14

RITAZAREM

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Arthritis Research UK

Genentech, Inc.

Roche Pharma AG

University of Pennsylvania