Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis
NCT ID: NCT06611696
Last Updated: 2025-05-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE4
160 participants
INTERVENTIONAL
2024-11-15
2028-09-30
Brief Summary
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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 (remission/relapse), 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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Glucocorticoid group
Prednisolone will be commenced with dose of 0.5mg/kg/day and will be tapered and off within 5 months. If a patient fails to achieve BVAS=0 or normalization of CRP levels or normalization of ANCA levels, an investigator can keep 5mg/day of prednisolone and postpone the procedure of stopping prednisolone. Patients will also receive rituximab (375mg/m2/w x4).
During remission maintenance phase (6-24 months),, patients will receive rituximab (500mg/body) every 6 months as remission maintenance therapy.
In the case of inadequate response to the combination therapy of prednisolone and rituximab, additional administration of prednisolone 20mg/day (less than 2 weeks) can be allowed as the rescue therapy.
During remission maintenance phase, in the case of minor relapse, additional administration of prednisolone 20mg/day (less than 2 weeks) can be allowed as the rescue therapy. Minor relapse is defined as relapse with no major BVAS item.
Prednisolone and rituximab
Patients in the glucocorticoid arm will be treated with reduced-dose prednisolone and rituximab.
Avacopan group
Prednisolone will be commenced with dose of 0.5mg/kg/day and will be tapered and off within 1 months. Patients will also receive avacopan (60mg/day) and rituximab (375mg/m2/w x4).
During remission maintenance phase (6-24 months), patients will receive avacopan (60mg/day) as remission maintenance therapy until the trial end.
In the case of inadequate response to the combination therapy of avacopan, prednisolone and rituximab, additional administration of prednisolone 20mg/day (less than 2 weeks) can be allowed as the rescue therapy.
During remission maintenance phase, in the case of minor relapse, additional administration of prednisolone 20mg/day (less than 2 weeks) can be allowed as the rescue therapy. Minor relapse is defined as relapse with no major BVAS item.
Avacopan, prednisolone and rituximab
Patients in the avacoapn group will be treated with avacoapn, short-term reduced-dose prednisolone and rituximab.
Interventions
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Avacopan, prednisolone and rituximab
Patients in the avacoapn group will be treated with avacoapn, short-term reduced-dose prednisolone and rituximab.
Prednisolone and rituximab
Patients in the glucocorticoid arm will be treated with reduced-dose prednisolone and rituximab.
Eligibility Criteria
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Inclusion Criteria
2. Age=\>18 years
3. New clinical diagnosis of ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis) consistent with the 2012 Chapel Hill consensus definitions and 2022 EULAR/ACR classification criteria
4. Positive test by ELISA, CLEIA or FEIA for proteinase 3-ANCA or myeloperoxidase-ANCA
Exclusion Criteria
2. ANCA-associated vasculitis related glomerulonephritis (eGFR less than 15ml/min) or alveolar hemorrhage (oxygen inhalation more than 2L/min)
3. Presence of another multisystem autoimmune disease
4. Known infection with HIV; a past or current history of hepatitis B virus or hepatitis C virus infection
5. Desire to bear children, pregnancy or lactating
6. History of malignancy within the past 5 years or any evidence of persistent malignancy
7. Ongoing or recent (last 1 year) evidence of active tuberculosis
8. History of severe allergy or anaphylaxis to monoclonal antibody therapy
9. Any concomitant condition anticipated to likely require oral systemic glucocorticoids, immunosuppressants, biologics, plasma exchange or IVIg
10. Any biological B cell depleting agent (such as rituximab or belimumab)-use within the past 6 months
11. Past history of medication of avacopan
12. Patients can not take avacopan and prednisolone orally
13. Other conditions, in the investigator\'s opinion, inappropriate for the trial entry
18 Years
ALL
No
Sponsors
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Kissei Pharmaceutical Co., Ltd.
INDUSTRY
International University of Health and Welfare
OTHER
Chiba University
OTHER
Responsible Party
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Shunsuke Furuta
Associate Professor, Department of Allergy and Clinical Immunology
Principal Investigators
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Masayoshi Harigai, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
International University of Health and Welfare
Locations
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Fujita Health University Hospital
Toyoake, Aichi-ken, Japan
Asahi General Hospital
Asahi, Chiba, Japan
Chiba Aoba Municipal Hospital
Chiba, Chiba, Japan
Chiba University
Chiba, Chiba, Japan
Chiba Rosai Hospital
Ichihara, Chiba, Japan
Kameda Medical Centre
Kamogawa, Chiba, Japan
International University of Health and Welfare
Narita, Chiba, Japan
Japanese Red Cross Narita Hospital
Narita, Chiba, Japan
Gunma University
Maebashi, Gunma, Japan
Kagawa University
Hiragi, Kagawa-ken, Japan
St.Marianna University School of Medicine
Kawasaki, Kanagawa, Japan
Tohoku Univerisity
Sendai, Miyagi, Japan
Nagasaki University
Nagasaki, Nagasaki, Japan
Okayama University
Okayama, Okayama-ken, Japan
Kitano Hospital
Osaka, Osaka, Japan
Saitama Medical University
Kawagoe, Saitama, Japan
Dokkyo Medical University
Mibu, Tochigi, Japan
Juntendo Univeristy
Bunkyoku, Tokyo, Japan
Kyorin University
Mitaka, Tokyo, Japan
Toho University
Ōta-ku, Tokyo, Japan
Teikyo University
tabashi City, Tokyo, Japan
Yamanashi University
Chuo-shi, Yamanashi, Japan
Countries
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Central Contacts
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Facility Contacts
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References
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Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage CO, Adu D. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997 Feb;40(2):371-80. doi: 10.1002/art.1780400222.
Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, Flossmann O, Hall C, Hollywood J, Jayne D, Jones R, Lanyon P, Muir A, Scott D, Young L, Luqmani RA. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009 Dec;68(12):1827-32. doi: 10.1136/ard.2008.101279. Epub 2008 Dec 3.
Suppiah R, Robson JC, Grayson PC, Ponte C, Craven A, Khalid S, Judge A, Hutchings A, Merkel PA, Luqmani RA, Watts RA; DCVAS INVESTIGATORS. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):321-326. doi: 10.1136/annrheumdis-2021-221796. Epub 2022 Feb 2.
Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, Khalid S, Hutchings A, Watts RA, Merkel PA, Luqmani RA; DCVAS Investigators. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):315-320. doi: 10.1136/annrheumdis-2021-221795. Epub 2022 Feb 2.
Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764.
Furuta S, Nakagomi D, Kobayashi Y, Hiraguri M, Sugiyama T, Amano K, Umibe T, Kono H, Kurasawa K, Kita Y, Matsumura R, Kaneko Y, Ninagawa K, Hiromura K, Kagami SI, Inaba Y, Hanaoka H, Ikeda K, Nakajima H; LoVAS Collaborators. Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis: A Randomized Clinical Trial. JAMA. 2021 Jun 1;325(21):2178-2187. doi: 10.1001/jama.2021.6615.
Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. No abstract available.
Study Documents
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Document Type: Study Protocol
Regarding deidentified patient data, please request to Dr Shunsuke Furuta at [email protected] or Dr Masayoshi Harigai at [email protected] after publishing pre-defined trial results.
View DocumentRelated Links
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English version of the protocol is now preparing and will be shown in the above website.
Other Identifiers
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CRB0097-24
Identifier Type: -
Identifier Source: org_study_id
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