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ANCA Associated Vasculitis (AAV)Phase 4ARRIANCT06611696

Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis

A Phase 4 study testing Avacopan, prednisolone and rituximab and Prednisolone and rituximab in people with ANCA Associated Vasculitis (AAV), run by Chiba University at 22 sites in Japan.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ANCA Associated Vasculitis (AAV)
What is being tested?
Avacopan, prednisolone and rituximab and Prednisolone and rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
22 sitesJapan
Study dates
15 Nov 2024to 30 Sep 2028
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Shunsuke Furuta, MD, PhD contact

81+43-222-7171 ext. 5531

shfuruta@chiba-u.jp

22 sites in 1 country

Japan22 sites, 22 recruiting

  • Asahi General Hospital

    Asahi, Chiba, 2892511

    ShinIchiro Kagami, MD, PhD, 81+0479-63-8111, kagami@hospital-asahi.jp

    Recruiting

  • Juntendo Univeristy

    Bunkyoku, Tokyo, 1138431

    Naoto Tamura, MD, PhD, 81+03-3813-3111, tnaoto@juntendo.ac.jp

    Recruiting

  • Chiba Aoba Municipal Hospital

    Chiba, Chiba, 2600852

    Yoshihisa Kobayashi, MD, PhD, 81+043-227-1131, yoshikoba7923@yahoo.co.jp

    Recruiting

  • Chiba University

    Chiba, Chiba, 2608677

    Shunsuke Furuta, MD, PhD, 81+432227171 ext. 5531, shfuruta@chiba-u.jp

    Recruiting

  • Yamanashi University

    Chuo-shi, Yamanashi, 4093898

    Daiki Nakagomi, MD, PhD, 81+055-273-3113, dnakagomi@yamanashi.ac.jp

    Recruiting

  • Kagawa University

    Hiragi, Kagawa-ken, 7610793

    Hiroaki Dobashi, MD, PhD, 81+087-898-5111, dobashi.hiroaki@kagawa-u.ac.jp

    Recruiting

  • Chiba Rosai Hospital

    Ichihara, Chiba, 2900003

    Tomohiro Tamachi, MD, PhD, 81+0436-74-1111, tamachit@chiba-u.jp

    Recruiting

  • Kameda Medical Centre

    Kamogawa, Chiba, 2968602

    Tomo Suzuki, MD, 81+04-7092-2211, suzuki.tomo@kameda.jp

    Recruiting

  • Saitama Medical University

    Kawagoe, Saitama, 3508550

    Takahiko Kurasawa, MD, PhD, 81+049-228-3574, t_kura@saitama-med.ac.jp

    Recruiting

  • St.Marianna University School of Medicine

    Kawasaki, Kanagawa, 2168511

    Kimito Kawahata, MD, PhD, 81+044-977-8111, kimito.kawahata@marianna-u.ac.jp

    Recruiting

  • Gunma University

    Maebashi, Gunma, 3718511

    Keijyu Hiromura, MD, PhD, 81+027-220-7111, hiromura@gunma-u.ac.jp

    Recruiting

  • Dokkyo Medical University

    Mibu, Tochigi, 3210293

    Kei Ikeda, MD, PhD, 81+0282-86-1111, k-ikeda847@dokkyomed.ac.jp

    Recruiting

  • Kyorin University

    Mitaka, Tokyo, 1818611

    Yoshinori Komagata, MD, PhD, 81+0422-47-5511, komagata@ks.kyorin-u.ac.jp

    Recruiting

  • Nagasaki University

    Nagasaki, Nagasaki, 8528501

    Atsushi Kawakami, MD, PhD, 81+095-819-7200, atsushik@nagasaki-u.ac.jp

    Recruiting

  • International University of Health and Welfare

    Narita, Chiba, 2868520

    Masayoshi Harigai, MD, PhD, 81+0476-35-5600, mharigai@iuhw.ac.jp

    Recruiting

  • Japanese Red Cross Narita Hospital

    Narita, Chiba, 2868523

    Masaki Hiraguri, MD, 81+0476-22-2311, hiraguri@naritasekijyuji.jp

    Recruiting

  • Okayama University

    Okayama, Okayama-ken, 7008558

    Yoshinori Matsumoto, MD, PhD, 81+086-235-7235, ymatsumoto@okayama-u.ac.jp

    Recruiting

  • Kitano Hospital

    Osaka, Osaka, 5308480

    Tomomi Endo, MD, 81+06-6312-1221, t-endou1106@kitano-hp.or.jp

    Recruiting

  • Toho University

    Ōta-ku, Tokyo, 1438541

    Toshihiro Nanki, MD, PhD, 81+03-3762-4151, toshihiro.nanki@med.toho-u.ac.jp

    Recruiting

  • Tohoku Univerisity

    Sendai, Miyagi, 9808574

    Hiroshi Fujii, MD, PhD, 81+022-717-7000, hfujii@med.tohoku.ac.jp

    Recruiting

  • Teikyo University

    tabashi City, Tokyo, 1738606

    Hajime Kono, MD, PhD, 81+03-3964-1211, kono@med.teikyo-u.ac.jp

    Recruiting

  • Fujita Health University Hospital

    Toyoake, Aichi-ken, 4701192

    Naotake Tsuboi, MD, PhD, 81+0562-93-2111, nao-take@fujita-hu.ac.jp

    Not yet recruiting

Other trials in Japan

About this study

Official title: Avacopan With Short-term Reduced-dose Glucocorticoids vs Reduced-dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-associated Vasculitis

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?

Read more

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.

Read the 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.

Being tested
Avacopan, prednisolone and rituximab, Prednisolone and rituximab
Keywords
microscopic polyangiitis, granulomatosis with polyangiitis, avacopan, ANCA-associated vasculitis
Medical subject headings
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis, Granulomatosis with Polyangiitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Avacopan, prednisolone and rituximabDrug

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

  • Prednisolone and rituximabDrug

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

Study groups in NCT06611696
Study groupRoleWhat they receive
Glucocorticoid groupActive comparatorPrednisolone 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.
Receives: Drug: Prednisolone and rituximab
Avacopan groupExperimentalPrednisolone 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.
Receives: Drug: Avacopan, prednisolone and rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportions of patients achieving remission

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

    Measured: 26 weeks

Secondary outcomes (18)

  1. Sustained remission without taking prednisolone at 104 weeks

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

    Measured: 104 weeks

  2. Survival, relapse and end-stage renal disease

    Assessed by Kaplan-Meier curves.

    Measured: 26 and 104 weeks

  3. Accumulative dose of glucocorticoids

    Accumulative dose of glucocorticoids during the study period

    Measured: 26 and 104 weeks

  4. Birmingham Vasculitis Activity Score (BVAS) version 3

    BVAS is a scoring system for assessing the disease activity of vasculitis.

    Measured: 26 and 104 weeks

  5. Vasculitis Damage Index (VDI)

    VDI is a scoring system for assessing irreversible disease damage due to vasculitis.

    Measured: 104 weeks

  6. Short-Form 36 (SF-36)

    SF-36 is a scoring system for assessing patient QOL.

    Measured: 26 and 104 weeks

  7. Serious adverse event (SAE)

    Event numbers and proportions of patients with one or more SAEs.

    Measured: 26 and 104 weeks

  8. Proportions of the patients with new onset diabetes mellitus

    Diabetes mellitus requiring drug treatments

    Measured: 26 and 104 weeks

  9. Proportions of the patients with new onset hypertension

    Hypertension requiring drug treatments

    Measured: 26 and 104 weeks

  10. Proportions of the patients with new onset hyperlipidemia

    Hyperlipidemia requiring drug treatments

    Measured: 26 and 104 weeks

  11. Proportion of the patients with new onset bone fracture, bone density

    Bone density is assessed at lumber spines.

    Measured: 104 weeks

  12. Number of infections, proportions of the patients with infection

    Infections requiring drug treatments

    Measured: 26 and 104 weeks

  13. Number of serious infections, proportions of the patients with serious infection

    Serious infections are serious events among infections requiring drug treatments.

    Measured: 26 and 104 weeks

  14. Proportions of the patients with liver dysfunction

    Liver dysfunction \>= grade 3 liver dysfunction (CTCAE)

    Measured: 26 and 104 weeks

  15. Proportions of the patients with new onset malignancies

    Malignancies diagnosed after the trial entry

    Measured: 26 and 104 weeks

  16. Proportions of patients achieving remission without the rescue therapy

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

    Measured: 26 weeks

  17. Sustained remission without taking prednisolone at 104 weeks and the rescue therapy during the trial period

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

    Measured: 104 weeks

  18. Proportions of patients treated with the rescue therapy

    Details of the rescue therapy are written in the section of "Arms and Interventions".

    Measured: 26 and 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2024
  2. Study start15 Nov 2024
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion30 Sep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06611696
Sponsor's protocol ID
CRB0097-24
Acronym
ARRIA
Status last verified
Nov 2024
First submitted
22 Sep 2024
Last updated
4 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Deidentified participant data

Publications

  • 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.

    PubMed 9041949

  • 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.

    PubMed 19054820

  • 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.

    PubMed 35110332

  • 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.

    PubMed 35110333

  • 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.

    PubMed 36927642

  • 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.

    PubMed 34061144

  • 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.

    PubMed 33596356

  • 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.

    PubMed 23045170

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Avacopan, prednisolone and rituximab and Prednisolone and rituximab in people with ANCA Associated Vasculitis (AAV), run by Chiba University at 22 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shunsuke Furuta, MD, PhD (81+43-222-7171 ext. 5531, shfuruta@chiba-u.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportions of patients achieving remission (time frame: 26 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06611696, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

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