1 For visit windows please refer to protocol.
2 Assessments done within 14 days of baseline visit do not have to be repeated at the discretion of the investigator.
3 Until common closing date.
4 The screening visit must be completed within 14 days of the baseline visit.
5 Should be completed before the participant sees the physician, undergoes any tests or treatment, or receives any tests that day EXCEPTION: Screening Visit.
6 Candida and tetanus booster formulation used. Note: skin test placement is required before starting the baseline infusion. Skin test readings are not required prior to infusion.) To be
repeated for testing immunotolerance in a subset of participants after month 6 (see section 9)
7 Within the last 30 days at the screening visit
8 Not applicable after V12 or termination visit.
9 During the infusion, every 15 minutes for 1 hour; then every 30 minutes; and then at least 1 hour after the completion of the infusion.
10 Not applicable after V12 or termination visit.
11 At baseline/V1 to Week 3/V4 if clinically indicated.
12 CXR is required at either baseline or screening and months 1, 6, 9, 18 for all participants; and at months 2,4,12 and 15 for participants with abnormal CXR at any visit. CXRs obtained
within 2 weeks of a study visit does not have to be repeated at the investigator's discretion. CT scans can be performed instead of CXRs at the investigator's discretion.
13 After screening, an ECG must be done at V10, V12, and when the participant withdraws or terminates from the study.
14 Flare history not required at screening and baseline.
15 STAT on V2-V4. If a pre-infusion WBC <3,000/mm3 is noticed, the infusion should be withheld; hematology includes WESR; does not need to be repeated at baseline if not clinically
16 Chemistry includes only BUN, creatinine, and C-reactive protein; it does not need to be repeated at baseline if not clinically indicated
17 The clinical ANCA testing performed at the screening visit will be done locally and will determine the participant’s eligibility.
18 TPMT specimens will be drawn at screening, but results are not required for randomization. TPMT may determined by TPMT testing or a completed AZA course of at least
19 Only for women of child-bearing potential
20 Does not need to be repeated at baseline if not clinically indicated
21 Also to be done at time of flare and switchover (discontinuation of CYC and start of AZA).
22 For mechanistic assays. Not carried out locally
23 See the manual of operation.
24 A maximum of three 1-day glucocorticoid IV doses can be administered. Last glucocorticoid infusion must be given within 14 days before the first rituximab/placebo infusion.
Infusion 1 and IV steroid can be administered on the same day. See section 6.1 for the roles of the investigator versus the role of the safety officer during the infusion.
25 Participants will be premedicated with diphenhydramine (50 mg) and acetaminophen (650 mg) orally 1 hour (plus or minus 15 minutes) before each infusion. The infusion will be
administered in a monitored setting, with access to resuscitative drugs, monitoring devices, and CPR equipment.
26 CYC/CYC placebo during remission induction phase; AZA/AZA placebo during remission maintenance phase. Participants will be switched over from CYC/CYC placebo to
AZA/AZA placebo between 3-6 months as per protocol.