Protocol Synopsis V1.1 - Rare Disease

EudraCT number: 2012-001102-14 Page 11 of 42permitted GC regimens:Oral prednisone (prednisolone will beallowed), commencing at 1.0mg/kg/day(maximum 60 mg/day),or 0.5mg/kg/day (maximum 30 mg/day),both reducing to 10mg/day by month 3 (Seeschedule 1, pg. 26).Maximum daily dose of GC is 60 mgprednisone in week 0. Round down to thenearest 5 mg above 20 mg. Round down tothe nearest 2.5 mg below 20 mg. GC to beadministered in a single daily dose.Intravenous (IV) GCs are not mandated bythe protocol. At the investigator’s discretion,patients may receive up to a maximumcumulative dose of 3000mg IVmethylprednisolone, between 14 days prior toenrolment and 7 days after enrolment.Glucocorticoids in Maintenance Phase:Maximum Treatment DurationSummary of Study ProceduresScreening:Baseline:A GC dose of prednisolone 10 mg/day or lessis a requirement for randomisation. GCreduces to 5 mg/day by month 6, accordingto schedule 2 (pg. 26). At month 16, GCdose is reduced to 2.5mg/day and at month20 GC are completely withdrawn.Treatment is protocolised for the entireduration of the study, until the common closedate, when the final patient recruited hascompleted 36 months within the study oruntil the patient has completed 48 months onstudy whichever the sooner. Patients in therituximab arm will receive treatment untilmonth 20, and those in the azathioprine armuntil month 27.Procedures to establish inclusion/exclusioncriteria.Baseline data will include:1. Date of birth, sex, limited medicalhistory2. Medications, including prior AAVtreatments3. Height/weight4. Disease activity assessment(BVAS/WG)5. Disease related damage assessment(CDA)6. Patient self-reported SF-36questionnaire, EQ5D questionnaire andRITAZAREM Version Number: 2.0 Date: 3 rd October 2013