Rituximab Vasculitis Maintenance Study



Status:Active, not recruiting
Conditions:Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases
Healthy:No
Age Range:15 - Any
Updated:2/13/2019
Start Date:April 2013
End Date:December 2019

Use our guide to learn which trials are right for you!

An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis

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.

Patients will be recruited at the time of relapse. All will receive rituximab 375 mg/m2/week
x 4 and glucocorticoids.

Those patients that achieve disease control (BVAS/WG ≤ 1 and daily prednisone dose ≤ 10 mg)
by month 4 will be randomised to the rituximab or control remission maintenance groups.

Treatment is protocolised for the entire duration of the study, until the common close date,
when the final patient recruited has completed 36 months within the study or until the
patient has completed 48 months on study whichever the sooner. Patients in the rituximab arm
will receive treatment until month 20, and those in the azathioprine arm until month 27.

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
We found this trial at
9
sites
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
8700 Beverly Blvd # 8211
Los Angeles, California 90048
(1-800-233-2771)
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
University of Utah Research is a major component in the life of the U benefiting...
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
500 S State St
Ann Arbor, Michigan 48109
(734) 764-1817
University of Michigan The University of Michigan was founded in 1817 as one of the...
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Chapel Hill, North Carolina 27599
(919) 962-2211
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
535 E 70th St
New York, New York 10021
(212) 606-1000
Hospital for Special Surgery Founded in 1863, Hospital for Special Surgery is the nation
?
mi
from
New York, NY
Click here to add this to my saved trials
3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: Peter Merkel, MD
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Rochester, Minnesota 55905
?
mi
from
Rochester, MN
Click here to add this to my saved trials