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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01697267




Registration number
NCT01697267
Ethics application status
Date submitted
31/08/2012
Date registered
2/10/2012

Titles & IDs
Public title
Rituximab Vasculitis Maintenance Study
Scientific title
An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis
Secondary ID [1] 0 0
2012-001102-14
Secondary ID [2] 0 0
RITAZAREM
Universal Trial Number (UTN)
Trial acronym
RITAZAREM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis 0 0
Microscopic Polyangiitis 0 0
Wegener Granulomatosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Rituximab
Treatment: Drugs - Azathioprine

Experimental: Rituximab Maintenance - Rituximab maintenance: 1g at 4, 8, 12, 16 \& 20 months with standardised steroid taper

Active comparator: Azathioprine Maintenance - Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27.


Treatment: Other: Rituximab
Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.

Treatment: Drugs: Azathioprine
Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27.

The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily.

If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relapse-free Survival
Timepoint [1] 0 0
Any patients who have not relapsed at up to a maximum of 4 years will be censored.
Secondary outcome [1] 0 0
Number of Participants in Remission at 24 and 48 Months
Timepoint [1] 0 0
24 and 48 months
Secondary outcome [2] 0 0
Combined Damage Assessment Score (Disease Related Damage Assessment)
Timepoint [2] 0 0
data in Rows represent the change from randomization (month 4) to months 12, 24, 36, and 48.
Secondary outcome [3] 0 0
Cumulative GC Exposure
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Severe Adverse Event Rate
Timepoint [4] 0 0
Up to 48 months
Secondary outcome [5] 0 0
Infection Rates
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Health-related Quality of Life Using the SF-36 Physical Composite
Timepoint [6] 0 0
4 months
Secondary outcome [7] 0 0
Health-related Quality of Life Using the SF-36 Mental Composite
Timepoint [7] 0 0
4 months
Secondary outcome [8] 0 0
Health-related Quality of Life Using the SF-36 Physical Composite
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Health-related Quality of Life Using the SF-36 Mental Composite
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Health-related Quality of Life Using the SF-36 Physical Composite
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Health-related Quality of Life Using the SF-36 Mental Composite
Timepoint [11] 0 0
24 months
Secondary outcome [12] 0 0
Health-related Quality of Life Using the SF-36 Physical Composite
Timepoint [12] 0 0
36 months
Secondary outcome [13] 0 0
Health-related Quality of Life Using the SF-36 Mental Composite
Timepoint [13] 0 0
36 months
Secondary outcome [14] 0 0
Health-related Quality of Life Using the SF-36 Physical Composite
Timepoint [14] 0 0
48 months
Secondary outcome [15] 0 0
Health-related Quality of Life Using the SF-36 Mental Composite
Timepoint [15] 0 0
48 months

Eligibility
Key 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
Minimum age
15 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/11/2019
Sample size
Target
Accrual to date
Final
188
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Czechia
State/province [10] 0 0
Prague
Country [11] 0 0
Ireland
State/province [11] 0 0
Cork
Country [12] 0 0
Italy
State/province [12] 0 0
Parma
Country [13] 0 0
Japan
State/province [13] 0 0
Okayama
Country [14] 0 0
Japan
State/province [14] 0 0
Chiba-shi
Country [15] 0 0
Japan
State/province [15] 0 0
Kyoto
Country [16] 0 0
Japan
State/province [16] 0 0
Miyazaki
Country [17] 0 0
Japan
State/province [17] 0 0
Tokyo
Country [18] 0 0
New Zealand
State/province [18] 0 0
Auckland
Country [19] 0 0
Sweden
State/province [19] 0 0
Stockholm
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Leicestershire
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Birmingham
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Brighton
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Cambridge
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Dudley
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Ipswich
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Leeds
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Middlesbrough
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Nottingham
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Other
Name
Cambridge University Hospitals NHS Foundation Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Arthritis Research UK
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Roche Pharma AG
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Genentech, Inc.
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Pennsylvania
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Jayne
Address 0 0
Cambridge University Hospitals NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01697267