UMIN-CTR Clinical Trial

Basic information
Public title	An international, open label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA-associated vasculitis
Acronym	RITAZAREM
Scientific Title	An international, open label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA-associated vasculitis
Scientific Title:Acronym	RITAZAREM
Region	Japan North America South America Australia Europe

Condition
Condition	Granulomatosis With Polyangiitis (Wegener's) Microscopic Polyangiitis
Classification by specialty	Medicine in general Nephrology Clinical immunology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	To demonstrate the superiority of rituximab against azathioprine in the prevention of disease flare in AAV patients with relapsing disease
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	Time to disease relapse (either minor or major relapse) from randomisation
Key secondary outcomes	1. Proportion of patients who maintain remission at 24 and 48 months 2. Time to a major or second minor relapse 3. Cumulative accrual of damage as measured by the combined damage assessment score (CDA) 4. Health-related quality of life as measured using SF-36 5. Cumulative glucocorticoid exposure 6. Severe adverse event rate 7. Infection rate

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Experimental: Rituximab Maintenance. Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper.
Interventions/Control_2	Active Comparator: Azathioprine Maintenance. Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation). Azathioprine withdrawn at month 27.
Interventions/Control_3
Interventions/Control_4
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Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
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Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Participants must meet all of the following criteria to be eligible for enrolment: 1). Written informed consent 2). A diagnosis of AAV (granulomatosis with polyangiitis (Wegener's) 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 induction therapy 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.
Key exclusion criteria	1). Age < 18 years. 2). Previous therapy with: a). Any biological B cell depleting agent within the past 6 months b). Alemtuzumab or anti-thymocyte globulin within the last 12 months; c). IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months; d). 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: a). Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation; b). Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis; c). 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); d). History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies; e). Known infection with HIV, a past or current history of hepatitis B virus or hepatitis C virus infection; f). Ongoing or recent (last 12 months) evidence of active tuberculosis or known active infection 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; h). Pregnancy or inadequate contraception in pre-menopausal women; i). Breast feeding or lactating. 4. Exclusion criteria related to laboratory parameters: a). Bone marrow suppression; b). Elevation of Aspartate aminotransferase or alanine aminotransferase or amylase
Target sample size	190

Research contact person
Name of lead principal investigator	1st name Middle name Last name Shouichi Fujimoto
Organization	University of Miyazaki Hospital
Division name	Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki
Zip code
Address	5200 Kihara, Kiyotake-cho, Miyazaki 889-1692 Japan
TEL	0985-85-1510
Email	fujimos@fc.miyazaki-u.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Toshiko Ito-Ihara
Organization	Kyoto University Hospital
Division name	Institute for Advancement of Clinical and Translational Science
Zip code
Address	54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507 Japan
TEL	075-751-4739
Homepage URL	http://rarediseasesnetwork.epi.usf.edu/vcrc/ritazarem/
Email	itoshi@kuhp.kyoto-u.ac.jp

Sponsor
Institute	University of Miyazaki Hospital
Institute
Department

Funding Source
Organization	Grants from Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	The European Vasculitis Society Vasculitis Clinical Research Consortium
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
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Secondary IDs
Secondary IDs	YES
Study ID_1	NCT01697267
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2	2012-001102-14
Org. issuing International ID_2	EUDRACT
IND to MHLW

Institutions
Institutions	宮崎大学医学部附属病院 University of Miyazaki, Miyazaki、田附興風会医学研究所北野病院 Kitano Hospital, Osaka、千葉大学医学部附属病院 Chiba University, Chiba、岡山大学病院 Okayama University, Okayama、帝京大学医学部附属病院 Teikyo Univesity, Tokyo、杏林大学医学部付属病院 Kyorin University, Tokyo、東京都健康長寿医療センター Tokyo Metropolitan Geriatric Hospital, Tokyo.

Other administrative information
Date of disclosure of the study information	2013 Year 12 Month 04 Day

Related information
URL releasing protocol	http://rarediseasesnetwork.epi.usf.edu/vcrc/ritazarem/
Publication of results	Unpublished

Result
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Number of participants that the trial has enrolled
Results
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Results Delayed
Results Delay Reason
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Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 07 Month 19 Day
Date of IRB	2014 Year 01 Month 31 Day
Anticipated trial start date	2014 Year 06 Month 26 Day
Last follow-up date	2019 Year 10 Month 30 Day
Date of closure to data entry	2019 Year 12 Month 31 Day
Date trial data considered complete	2020 Year 03 Month 30 Day
Date analysis concluded	2020 Year 06 Month 30 Day

Other
Other related information

Management information
Registered date	2013 Year 11 Month 26 Day
Last modified on	2019 Year 12 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014524

Research Plan
Registered date	File name

Research case data specifications
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Research case data
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