RITAZAREM: A trial of rituximab versus azathioprine for maintenance of remission in ANCA vasculitis

• Register: EUCTR
• Last refreshed on: 23 January 2017
• Main ID: EUCTR2012-001102-14-IE
• Date of registration: 14/08/2014
• Prospective Registration: Yes
• Primary sponsor: University College Cork , Ireland
• Public title: RITAZAREM: A trial of rituximab versus azathioprine for maintenance of remission in ANCA vasculitis
• Scientific title: An international, open label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA-associated vasculitis - RITAZAREM: Rituximab vasculitis maintenance study
• Date of first enrolment: 10/10/2014
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001102-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, Czech Republic, Denmark, Germany, Ireland, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: Clinical Research Reporting Officer
• Affiliation: University College Cork

• Name: Clinical Research Reporting Officer
• Affiliation: University College Cork

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent
2.A diagnosis of ANCA Associated Vasculitis (AAV) [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
3.Current or historical PR3/MPO ANCA positivity by ELISA
4.Disease flare 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 or mycophenolate mofetil)
5.Aged 15 years and over


Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion criteria:
1.Age less than 15 years (age less than 18 years at centres that do not treat paediatric patients)
2.Exclusions related to medication:
Previous therapy with:
a.Any biological B cell depleting agent (such as rituximab or belimumab) 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 (HIV testing will not be a requirement for trial entry); 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 (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.
h.Pregnancy or inadequate contraception in pre-menopausal women
i.Breast feeding or lactating women

4.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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

ANCA vasculitis.
MedDRA version: 18.0 Level: LLT Classification code 10047889 Term: Wegeners granulomatosis System Organ Class: 10047065 - Vascular disorders
MedDRA version: 18.0 Level: LLT Classification code 10047888 Term: Wegener's granulomatosis System Organ Class: 10047065 - Vascular disorders
MedDRA version: 18.0 Level: PT Classification code 10063344 Term: Microscopic polyangiitis System Organ Class: 10047065 - Vascular disorders
MedDRA version: 18.0 Level: PT Classification code 10050894 Term: Anti-neutrophil cytoplasmic antibody positive vasculitis System Organ Class: 10021428 - Immune system disorders

Intervention(s)

Trade Name: MabThera
Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Rituximab
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: Azathioprine
Product Name: Azathioprine
Pharmaceutical Form: Tablet
INN or Proposed INN: Azathioprine
CAS Number: 446-86-6
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 1-2

Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 2.5-10

Trade Name: Mycophenolate
Product Name: Mycophenolate
Pharmaceutical Form: Tablet
INN or Proposed INN: Mycophenolic acid
CAS Number: 24280-93-1
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 250-500

Primary Outcome(s)

Primary end point(s): The primary endpoint is the time to disease relapse (either minor or major relapse) from randomisation.

Secondary Objective: The secondary objectives are to demonstrate:
1. Sustained disease remission beyond the 24 month treatment period
2. Long term safety of rituximab administration
3. The optimal remission maintenance therapy in ANCA-associated vasculitis following induction of disease remission with rituximab

Main Objective: The principle research objective is to demonstrate the superiority of rituximab against azathioprine in the prevention of disease flare in ANCA-associated vasculitis patients with relapsing disease

Timepoint(s) of evaluation of this end point: The primary endpoint will be reported at 24 months after enrollment

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints:
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 (treated with either intravenous or oral antibiotics) rate

Timepoint(s) of evaluation of this end point: 3. The combined damage assessment score (CDA) is completed at months 0, 4, 12, 24, 36 and 48.
4. Health-related quality of life as measured using SF-36 is completed at months 0, 4, 12, 24, 36, 42 and 48.
6 & 7. Severe adverse event rate and infection (treated with either intravenous or oral antibiotics) rate will be monitored throughout the trial.

Secondary ID(s)

http://RareDiseasesNetwork.org/VCRC/RITAZAREM

2012-001102-14-CZ

NCT01697267

Ritazarem

Source(s) of Monetary Support

Arthritis Research UK

Roche