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.
157 studies on the registry are indexed under Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; 75 are open to participants now.
This study's enrollment of 140 is above the median of 34 across 116 interventional studies indexed under Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.
Browse Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis studies →Chiba University is the lead sponsor of 17 studies on the registry; 3 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Ran from Oct 2014 to primary completion in Dec 2019, 62 months.
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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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Studies of the drugs tested here: Rituximab · Corticosteroids
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis →
Chiba University