Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis

NCT06611696 | Recruiting Phase 4 DMC

• 1 other identifier: CRB0097-24
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 22

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 (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.

Conditions

ANCA Associated Vasculitis (AAV)

Keywords

microscopic polyangiitis; granulomatosis with polyangiitis; avacopan; ANCA-associated vasculitis

Outcome Measures

Primary Outcomes (1)

• Proportions of patients achieving remission

  Remission is defined as BVAS (Birmingham vasculitis activity score)=0 and less than 5mg/day of prednisolone.

  26 weeks

Secondary Outcomes (18)

• Sustained remission without taking prednisolone at 104 weeks

  104 weeks

• Survival, relapse and end-stage renal disease

  26 and 104 weeks

• Accumulative dose of glucocorticoids

  26 and 104 weeks

• Birmingham Vasculitis Activity Score (BVAS) version 3

  26 and 104 weeks

• Vasculitis Damage Index (VDI)

  104 weeks

Study Arms (2)

Glucocorticoid group

ACTIVE COMPARATOR

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.

Drug: Prednisolone and rituximab

Avacopan group

EXPERIMENTAL

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.

Drug: Avacopan, prednisolone and rituximab

Interventions

Avacopan, prednisolone and rituximab DRUG

Patients in the avacoapn group will be treated with avacoapn, short-term reduced-dose prednisolone and rituximab.

Avacopan group

Prednisolone and rituximab DRUG

Patients in the glucocorticoid arm will be treated with reduced-dose prednisolone and rituximab.

Glucocorticoid group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent by a patient or a surrogate decision maker
• Age=\>18 years
• 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
• Positive test by ELISA, CLEIA or FEIA for proteinase 3-ANCA or myeloperoxidase-ANCA

You may not qualify if:

• Prior treatment for ANCA-associated vasculitis before trial entry
• ANCA-associated vasculitis related glomerulonephritis (eGFR less than 15ml/min) or alveolar hemorrhage (oxygen inhalation more than 2L/min)
• Presence of another multisystem autoimmune disease
• Known infection with HIV; a past or current history of hepatitis B virus or hepatitis C virus infection
• Desire to bear children, pregnancy or lactating
• History of malignancy within the past 5 years or any evidence of persistent malignancy
• Ongoing or recent (last 1 year) evidence of active tuberculosis
• History of severe allergy or anaphylaxis to monoclonal antibody therapy
• Any concomitant condition anticipated to likely require oral systemic glucocorticoids, immunosuppressants, biologics, plasma exchange or IVIg
• Any biological B cell depleting agent (such as rituximab or belimumab)-use within the past 6 months
• Past history of medication of avacopan
• Patients can not take avacopan and prednisolone orally
• Other conditions, in the investigator\'s opinion, inappropriate for the trial entry

Sponsors & Collaborators

• Chiba University: lead
• Kissei Pharmaceutical Co., Ltd.: collaborator
• International University of Health and Welfare: collaborator

Study Sites (22)

Fujita Health University Hospital

Toyoake, Aichi-ken, 4701192, Japan

NOT YET RECRUITING

Asahi General Hospital

Asahi, Chiba, 2892511, Japan

RECRUITING

Chiba Aoba Municipal Hospital

Chiba, Chiba, 2600852, Japan

RECRUITING

Chiba University

Chiba, Chiba, 2608677, Japan

RECRUITING

Chiba Rosai Hospital

Ichihara, Chiba, 2900003, Japan

RECRUITING

Kameda Medical Centre

Kamogawa, Chiba, 2968602, Japan

RECRUITING

International University of Health and Welfare

Narita, Chiba, 2868520, Japan

RECRUITING

Japanese Red Cross Narita Hospital

Narita, Chiba, 2868523, Japan

RECRUITING

Gunma University

Maebashi, Gunma, 3718511, Japan

RECRUITING

Kagawa University

Hiragi, Kagawa-ken, 7610793, Japan

RECRUITING

St.Marianna University School of Medicine

Kawasaki, Kanagawa, 2168511, Japan

RECRUITING

Tohoku Univerisity

Sendai, Miyagi, 9808574, Japan

RECRUITING

Nagasaki University

Nagasaki, Nagasaki, 8528501, Japan

RECRUITING

Okayama University

Okayama, Okayama-ken, 7008558, Japan

RECRUITING

Kitano Hospital

Osaka, Osaka, 5308480, Japan

RECRUITING

Saitama Medical University

Kawagoe, Saitama, 3508550, Japan

RECRUITING

Dokkyo Medical University

Mibu, Tochigi, 3210293, Japan

RECRUITING

Juntendo Univeristy

Bunkyoku, Tokyo, 1138431, Japan

RECRUITING

Kyorin University

Mitaka, Tokyo, 1818611, Japan

RECRUITING

Toho University

Ōta-ku, Tokyo, 1438541, Japan

RECRUITING

Teikyo University

tabashi City, Tokyo, 1738606, Japan

RECRUITING

Yamanashi University

Chuo-shi, Yamanashi, 4093898, Japan

RECRUITING

Related Publications (8)

• 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.

  PMID: 9041949 BACKGROUND

• 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.

  PMID: 19054820 BACKGROUND

• 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.

  PMID: 35110332 BACKGROUND

• 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.

  PMID: 35110333 BACKGROUND

• 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.

  PMID: 36927642 BACKGROUND

• 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.

  PMID: 34061144 BACKGROUND

• 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.

  PMID: 33596356 BACKGROUND

• 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.

  PMID: 23045170 BACKGROUND

Related Links

• English version of the protocol is now preparing and will be shown in the above website.

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Granulomatosis with Polyangiitis

Interventions

avacopan; Prednisolone; Rituximab

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Masayoshi Harigai, MD, PhD

  International University of Health and Welfare

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shunsuke Furuta, MD, PhD

CONTACT

81+43-222-7171; shfuruta@chiba-u.jp

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Allergy and Clinical Immunology

Study Record Dates

• First Submitted: September 22, 2024
• First Posted: September 25, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: May 4, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publishing the report regarding all the pre-defined trial data.
• Access Criteria: Data requests should be sent to Dr Shunsuke Furuta at shfuruta@chiba-u.jp or Dr Masayoshi Harigai at mharigai@iuhw.ac.jp. The requests should be assessed and permitted according to the individual purposes of the requests.

Locations

JP (22)