April 08, 2014
Institutional Review Board, Hospital for Special Surgery
The safety of our participants is our top priority. The trial/study is approved and periodically reviewed by the Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.
Before enrolling in a clinical trial or research study, the investigator will explain the purpose of the trial/study, its expected benefits, any possible risks or side effects, and what your role will be. If you want to join the trial/study, you must sign informed consent documents. You can leave a trial/study at any time without penalty.
For further information, see Understanding Clinical Trials/Research Studies.
Jessica K Gordon, MD
Lindsay S. Lally, MD
Daniele R. Lerner, BA
Uzunma C. Udeh, BA
Nina U. Paddu, BA
Enrollment will be ongoing until 160 patients are randomized. It is anticipated that this will require 190 patients to be recruited. The trial has 3 phases and will last 48 months (Induction phase 0-4 months, Maintenance phase 4-24 months, Long-term Follow-up a maximum of 24 months follow-up). During the induction phase of the trial patients will receive four infusions of Rituximab 375 mg/m2/week for four weeks. Patients that achieve disease control (BVAS/WG ≤ 1 and daily prednisone dose ≤ 10mg) by month 4 will be randomized to the rituximab or control remission maintenance groups. In the Rituximab Maintenance group patients will receive 1g of Rituximab at 4, 8, 12, 16 & 20 months and a standardized GC taper. In the follow-up phase patients will receive no therapy and follow-up between 36 and 48 months. In the Azathioprine Maintenance group patients will receive 2mg/kg/day with a standardized GC taper and in the follow-up phase AZA withdrawal at month 27 and a follow-up between 36 and 48 months.
Inclusion Criteria
1. Provided written informed consent
2. A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
3. Current or historical ANCA positivity either by ELISA or immunofluorescence
4. Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegener’s (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)
5. Ages 18-100
All patients will receive induction therapy with rituximab. Only those entering remission by 4 months will be randomised 1:1 to the rituximab or control groups
Exclusion Criteria
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 or 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.
g. 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.
7. Pregnancy or inadequate contraception in women of childbearing potential
8. Breast feeding or lactating
9. Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
Exclusion criteria related to laboratory parameters:
a) Bone marrow suppression as evidenced by a total white count < 4 x109/l, haemoglobin < 7 gm/dl or platelet count < 100,000/μl
b) Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis
Daniele Lerner
lernerd@hss.edu
646.714.6302