Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06611696
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-22
Brief Title:
Avacopan Vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Avacopan with Short-term Reduced-dose Glucocorticoids Vs Reduced-dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-associated Vasculitis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ARRIA
Brief Summary:
The goal of this clinical trial is to learn if avacopan in combination with short-term 4 weeks reduced-dose glucocorticoid and rituximab works to treat patients with newly-onset ANCA-associated vasculitis It will also learn about the long-term safety of avacopan The main questions it aims to answer are
Is avacopan in combination with short-term reduced-dose glucocorticoid and rituximab as effective as the combination of 20 week reduced-dose glucocorticoid and rituximab in the proportion of the patients achieving remission Does avacopan lower the relapse rate compared to the 6 monthly rituximab maintenance therapy What medical problems do participants have when taking long-term avacopan
Participants will
Be treated with avacopan in combination with short-term until 4 weeks reduced-dose glucocorticoid and rituximab at 0 week or reduced-dose glucocorticoid until 20 weeks and rituximab at 0 26 52 and 78 weeks
Be assessed at 0 4 8 16 26 52 78 and 104 weeks regarding disease status remissionrelapse disease activity by Birmingham Vasculitis Activity Score ver3 disease damage by Vasculitis Damage Index and adverse events
The primary endpoint is remission rates at 26 weeks
Is avacopan in combination with short-term reduced-dose glucocorticoid and rituximab as effective as the combination of 20 week reduced-dose glucocorticoid and rituximab in the proportion of the patients achieving remission Does avacopan lower the relapse rate compared to the 6 monthly rituximab maintenance therapy What medical problems do participants have when taking long-term avacopan
Participants will
Be treated with avacopan in combination with short-term until 4 weeks reduced-dose glucocorticoid and rituximab at 0 week or reduced-dose glucocorticoid until 20 weeks and rituximab at 0 26 52 and 78 weeks
Be assessed at 0 4 8 16 26 52 78 and 104 weeks regarding disease status remissionrelapse disease activity by Birmingham Vasculitis Activity Score ver3 disease damage by Vasculitis Damage Index and adverse events
The primary endpoint is remission rates at 26 weeks
Detailed Description:
Anti-neutrophil cytoplasm antibody ANCA-associated vasculitis is characterized by a small to medium-size vasculitis and the presence of ANCA ANCA-associated vasculitis includes microscopic polyangiitis granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis ANCA-associated vasculitis can be a life-threatening disease and the mortality is 80 at 1 year in untreated patients In 2010s standard therapies for remission induction of ANCA-associated vasculitis were the combination of high-dose glucocorticoids and either cyclophosphamide or rituximab Although those therapies have high remission rates of 80-90 mortality at 5 years is still high at 10-20 mainly due to treatments-related adverse events
In the LoVAS trial 2021 JAMA the combination of reduced-dose glucocorticoid and rituximab showed non-inferiority to high-dose glucocorticoid and rituximab in remission rates at 6 months In addition adverse events were dramatically less in the reduced-dose group than in the high-dose group
In the ADVOCATE trial 2021 NEJM the combination of avacopan newly developed complement C5a inhibitor and rituximab or cyclophosphamide showed non-inferiority to high-dose glucocorticoid and rituximab or cyclophosphamide in remission rates at 6 months The avacopan group was allowed to use glucocorticoid within 1 month from the trial entry and over 80 of patients used glucocorticoid indeed Regarding adverse events they were less in the avacopan group than in the glucocorticoid group
Although both the reduced-dose glucocorticoid regimen in the LoVAS trial and the avacopan regimen in the ADVOCATE trial are effective and safe for patients with ANCA-associated vasculitis there is no trial directly comparing both regimens at the moment Thus in this multicenter open-label randomized non-ineriority phase 4 trial the investigators aim to investigate if the combination of avacoapn short-term 4 weeks reduced-dose glucocorticoid and rituximab is non-inferior to the combination of reduced-dose glucocorticoid 20 weeks and rituximab The investigators also compare safety profiles and disease relapse between the two groups A total of 160 patients with new-onset ANCA-associated vasculitis microscopic polyangiitis and granulomatosis with polyangiitis will be recruited and randomized to the two treatments groups The primary end point is remission rate at 26 weeks and the patients will be followed until 104 weeks for assessing disease relapse and long-term safety
In the LoVAS trial 2021 JAMA the combination of reduced-dose glucocorticoid and rituximab showed non-inferiority to high-dose glucocorticoid and rituximab in remission rates at 6 months In addition adverse events were dramatically less in the reduced-dose group than in the high-dose group
In the ADVOCATE trial 2021 NEJM the combination of avacopan newly developed complement C5a inhibitor and rituximab or cyclophosphamide showed non-inferiority to high-dose glucocorticoid and rituximab or cyclophosphamide in remission rates at 6 months The avacopan group was allowed to use glucocorticoid within 1 month from the trial entry and over 80 of patients used glucocorticoid indeed Regarding adverse events they were less in the avacopan group than in the glucocorticoid group
Although both the reduced-dose glucocorticoid regimen in the LoVAS trial and the avacopan regimen in the ADVOCATE trial are effective and safe for patients with ANCA-associated vasculitis there is no trial directly comparing both regimens at the moment Thus in this multicenter open-label randomized non-ineriority phase 4 trial the investigators aim to investigate if the combination of avacoapn short-term 4 weeks reduced-dose glucocorticoid and rituximab is non-inferior to the combination of reduced-dose glucocorticoid 20 weeks and rituximab The investigators also compare safety profiles and disease relapse between the two groups A total of 160 patients with new-onset ANCA-associated vasculitis microscopic polyangiitis and granulomatosis with polyangiitis will be recruited and randomized to the two treatments groups The primary end point is remission rate at 26 weeks and the patients will be followed until 104 weeks for assessing disease relapse and long-term safety
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None