A Phase 4 interventional study of Rituximab and Glucocorticoids in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis and Wegener Granulomatosis, sponsored by Chiba University. Status unknown at 17 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2021-01-27.
Sponsored by Chiba University · Phase 4, Interventional, and Treatment
Previous reports suggested conventional immunosuppressants such as cyclophosphamide could not reduce glucocorticoid dose in remission induction in ANCA-associated vasculitis because of lower remission rate and higher relapse rate. However those reports didn't include rituximab.
B cell depletion therapy by rituximab is a new strategy for remission induction in ANCA-associated vasculitis. The RAVE and RITUXVAS trial (NEJM 2010, both) showed high-dose glucocorticoid plus rituximab had roughly the same efficacy and safety as high-dose glucocorticoid plus IV-cyclophosphamide. In addition, recent retrospective observational studies reported low-dose glucocorticoid plus rituximab led to re-induction in severe relapsing ANCA-associated vasculitis.
Thus, the investigators aim to investigate whether rituximab can reduce glucocorticoid dose in induction remission in ANCA-associated vasculitis (to show non-inferiority for efficacy between low-dose and high-dose glucocorticoid plus rituximab). Participants will be randomised to the "low-dose glucocorticoid plus rituximab" or the high-dose glucocorticoid plus rituximab" groups. Primary endpoint is proportion of remission at 6 months, then data regarding relapse and long-term safety will be collected until 24 months.
The study has been designed by the principal and coordinating investigators. It will include 140 participants from 18 hospitals in Japan. It is funded by Chiba University Hospital and Chiba East Hospital.
ANCA (anti-neutrophil cytoplasmic antibody)-associated vasculitis is characterised by small vessel vasculitis and presence of autoantibodies, ANCA. It can be a life-threatening disease with renal/respiratory failure. Current standard therapy in induction remission for ANCA-associated vasculitis is combination of high-dose glucocorticoid and IV-cyclophosphamide. This regimen is effective (remission rate; 80-90%), but often cause various glucocorticoid-related side effects. Especially, infection is related to death. Thus a new regimen reducing glucocorticoid dose is required.
Exclusion Criteria:
Prednisolone will be commenced with dose of 0.5mg/kg/day and will be tapered and off within 6 months. If a patient fails to achieve BVAS=0, an investigator can postpone the procedure of stopping prednisolone (prednisolone 5mg/day x 2 weeks, 4mg/day x 2 weeks, 3mg/day x 4 weeks, 2mg/day x 4 weeks, 1mg/day x 4 weeks, then off prednisolone). Once starting the procedure, prednisolone must be off after 16 weeks. Patients will also receive rituximab (375mg/m2/w x4). After achieving remission, patients will be receive rituximab (1g/body or 0.5g/bodyx2) every 6 months as remission maintenance therapy.
Drug: Rituximab · Drug: Glucocorticoids
Prednisolone will be commenced with dose of 1.0mg/kg/day and will be tapered to 10mg/day within 6 months. Patients will also receive rituximab (375mg/m2/w x4). After achieving remission, patients will be receive rituximab (1g/body or 0.5g/bodyx2) every 6 months as remission maintenance therapy. There's no limitation by the protocol regarding further prednisolone tapering.
Drug: Rituximab · Drug: Glucocorticoids
Patients will be administered rituximab (375mg/m2/w x4 infusions) for reducing glucocorticoid dose in remission induction phase.
Also known as: Rituxan
"Low-dose" group commenced 0.5mg/kg/day, then taper and stop within 6 months following pre-defined schedule. "High-dose" group commenced 1.0mg/kg/day, then taper to 10mg/day within 6 months following pre-defined schedule.
Also known as: Predonine, Prednisolone
Proportion of the patients achieving remission
Remission; BVAS ver.3=0 (or 1 with only one minor and persistent BVAS item) and prednisolone \<10mg/day
Time frame: 6 months
Time to remission
Remission; BVAS ver.3=0 (or 1 with only one minor and persistent BVAS item) and prednisolone \<10mg/day
Time frame: assessed at 1, 2, 4 and 6 months
Overall survival, disease free survival, time to end-stage renal disease, time to the first serious adverse event
Assessed by Kaplan-Meier curves
Time frame: 0-24 months
Proportions of death, relapse, end-stage renal disease and the composite of these
Assessed by Kaplan-Meier curves
Time frame: at 6 and 24 months
Proportions of major relapse
major relapse is relapse with one or more BVAS major items
Time frame: at 24 months
Birmingham Vasculitis Activity Score (BVAS) version 3
BVAS is a scoring system for assessing disease activity of vasculitis
Time frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months
Vasculitis Damage Index (VDI)
VDI is a scoring system for assessing irreversible disease damage due to vasculitis
Time frame: assessed at 0, 6, 12, 18 and 24 months
Short-Form 36 (SF-36)
SF-36 is a scoring system for assessing patient QOL.
Time frame: assessed at 0, 6, 12, 18 and 24 months
Patient global assessment (visualised analogue scale)
global assessments for disease activity and treatment toxicity
Time frame: assessed at 0, 6, 12, 18 and 24 months
Accumulative dose of glucocorticoids
Accumulative dose of glucocorticoids during the study period
Time frame: assessed at 6 and 24 months
Numbers of events of adverse events/serious adverse events, proportions of the patients with adverse events/serious adverse events
Event numbers and proportion of the patients with one or more events are assessed.
Time frame: at 6 and 24 months
Proportions of the patients with new onset diabetes mellitus
diabetes mellitus requiring drug treatments
Time frame: at 6 and 24 months
Proportion of the patients with new onset insomnia
insomnia requiring drug treatments
Time frame: at 6 and 24 months
Proportion of the patients with new onset bone fracture, bone density
bone density is assessed at lumber spines
Time frame: at 6 and 24 months
Number of infections, proportions of the patients with infection
infections requiring drug treatments
Time frame: at 6 and 24 months
Proportions of the patients with new onset hypertension
hypertension requiring drug treatments
Time frame: at 6 and 24 months
Proportions of the patients with new onset hyperlipidemia
hyperlipidemia requiring drug treatments
Time frame: at 6 and 24 months
Proportions of patients achieving remission and discontinuance of glucocorticoids
Remission is BVAS ver3=0 and prednisolone \<10mg/day.
Time frame: at 6 and 24 months
Serum immunoglobulin levels
Serum immunoglobulin levels
Time frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months
Peripheral blood B cell counts
CD19 positive B cells assessed by FACS
Time frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months
serum MPO-/PR3-ANCA levels measured by ELISA
MPO-ANCA and PR3-ANCA are disease specific autoantibodies binding neutrophil cytoplasmic antigen.
Time frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months
This study is status unknown, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.
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Granulomatosis with Polyangiitis→
Chiba University