NCT01697267

Rituximab Vasculitis Maintenance Study

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 188 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Microscopic Polyangiitis
• Wegener Granulomatosis

Interventions

Type	Name	Description
BIOLOGICAL	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.
DRUG	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%.

Timeline

• Start date: 2013-04-01
• Primary completion: 2018-11-22
• Completion: 2019-11-21
• First posted: 2012-10-02
• Last updated: 2022-03-18
• Results posted: 2022-03-18

Locations

38 sites across 10 countries: United States, Australia, Canada, Czechia, Ireland, Italy, Japan, New Zealand, Sweden, United Kingdom