ANCA-Associated Vasculitis (AAV)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune conditions affecting the small blood vessels in the body.¹ There are 3 distinct types of AAV: granulomatosis with polyangiitis (GPA), previously called Wegener’s granulomatosis; microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome.²

There is no known cure for AAV. Treatment and management of the condition currently relies on immunosuppressive and anti-inflammatory therapies, as well as complement inhibitor therapy. Current trials are testing potential treatment regimens for inducing and maintaining disease remission. Observational studies can also provide important information about the disease.

Clinical Trials That Are Active but No Longer Recruiting

There are some clinical trials that are ongoing but no longer recruiting participants. Some of these are for patients with GPA and/or MPA, while others are for patients with EGPA.

RITUXGOPRO

RITUXGOPRO (NCT03920722) is a small phase 3 clinical trial of 8 patients with MPA testing whether a Rituxan® (rituximab)-based treatment increases the remission rate and reduces the relapse-free survival rate compared to standard therapy with glucocorticoids alone. The trial is taking place in Paris, France and is expected to be completed in September 2023.³

COMBIVAS

COMBIVAS (NCT03967925) is a phase 2, randomized, double-blind, controlled mechanistic study assessing whether Rituxan plus Benlysta® (belimumab) could lead to improvements in biological endpoints, functional outcomes, and clinical status compared to Rituxan plus placebo. The study enrolled 31 adult participants with EGPA or MPA in the United Kingdom. It is due to be completed in November 2023.⁴ 

MAINRITSEG

MAINRITSEG (NCT03164473) is a phase 3, randomized, parallel-assignment study investigating the efficacy of Rituxan compared to Imuran® (azathioprine) maintenance therapy in terms of the duration of remission. It is being conducted in 98 adult patients with relapsing or newly diagnosed EGPA receiving standard of care therapy including glucocorticoid therapy reduction or withdrawal. The trial is taking place in Paris, France and is due to be completed in October 2024.⁵ 

ABROGATE

ABROGATE (NCT02108860) is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy of Orencia® (abatacept) in achieving sustained glucocorticoid-free remission in patients with relapsing nonsevere GPA. The trial involves 65 participants, aged 15 years and above, and it is due to be completed in September 2023.⁶

MANDARA

MANDARA (NCT04157348) is a phase 3, multicenter, randomized, double-blind, active-controlled, parallel-group study comparing the safety and efficacy of Fasenra® (benralizumab) with those of Nucala® (mepolizumab) in patients with relapsing or refractory EGPA who are already receiving corticosteroid therapy with or without stable immunosuppressive therapy.⁷ 

Following the completion of the 52-week double-blind treatment period, participants may be eligible to continue in an open-label extension study, which aims to allow each patient to receive Fasenra treatment for at least 1 year. The estimated completion date of the study is September 10, 2024.⁷

Read more about AAV treatment

Clinical Trials That Are Currently Recruiting Participants

There are several clinical trials currently recruiting patients with AAV.

SPARVASC

SPARVASC (NCT05630612) is a phase 2, randomized, double-blind, active-control, parallel-group study of 40 patients with AAV, aged 18 and over, who are in long-term remission. It aims to understand whether Filspari™ (sparsentan) benefits patients due to its abilities to lower blood pressure and block endothelin. Patients will either receive Filspari or Avapro® (irbesartan), which also lowers blood pressure but does not block endothelin. The trial is recruiting participants in the United Kingdom and aims to be completed on September 1, 2027.⁸

ENDURRANCE-1

ENDURRANCE-1 (NCT03942887) is currently recruiting 100 adult patients with GPA or MPA in the Netherlands to evaluate whether combining Rituxan with Cytoxan® (cyclophosphamide) is superior to the current standard of care with Rituxan only in inducing a favorable clinical and immunological state and therefore reducing the number of tailored re-treatments with Rituxan. The estimated completion date is April 1, 2025.⁹

E-Merge

E-merge (NCT05030155) is a randomized phase 3 clinical trial comparing a Nucala-based regimen with a conventional therapeutic strategy for the induction of remission in patients with EGPA. The trial is still enrolling an estimated 100 patients, aged 18 years and over, with EGPA regardless of ANCA status in France. The trial is due to be completed by May 2025.¹⁰

TAPIR

TAPIR (NCT01940094) is a multicenter, randomized, phase 3 clinical trial evaluating the effects of low-dose prednisone compared to stopping prednisone treatment altogether. Participants will taper their prednisone dose down to 5 mg per day or 0 mg per day for the duration of the study. The study is currently recruiting an estimated 159 participants with GPA, aged 18 years and above, in the United States and Canada, and it is expected to be completed in December 2023.¹¹

OCEAN

OCEAN (NCT05263934) is a phase 3 clinical trial investigating the safety and efficacy of depemokimab (GSK3511294) compared to those of Nucala in adult patients with relapsing or refractory EGPA receiving standard of care therapy. The trial aims to recruit an estimated 160 participants, aged 18 years and over, worldwide. It is expected to be completed on November 7, 2025.¹²

HAVEN

HAVEN (NCT04316494) is a multicenter, randomized, double-blind, placebo-controlled phase 4 trial testing whether Plaquenil® (hydroxychloroquine) could reduce disease activity in patients with AAV when added to background treatment. It is currently recruiting an estimated 76 participants, aged 18 years and over, in the United Kingdom. Its estimated completion date is December 2024.¹³

MAINEPSAN

MAINEPSAN (NCT03290456) is a study evaluating remission maintenance in systemic AAV using extended prednisone administration. Patients, aged 18 years and over, with GPA or MPA can apply to take part, regardless of ANCA status. The trial will take place at 45 different locations in France and is expected to be completed on June 4, 2024.¹⁴

LEFAZAREM

LEFAZAREM (NCT04737343) is a prospective, open-label, randomized, multicenter study aiming to verify that remission rate is not worse in patients treated with Arava® (leflunomide) than in those treated with Imuran. The trial is currently recruiting an estimated 114 participants in China. Patients with newly diagnosed or relapsing GPA, MPA, or EGPA who are in complete remission after combined treatment with glucocorticoids and pulse Cytoxan or Rituxan, aged 18 to 75 years, are eligible to participate. The full inclusion and exclusion criteria can be found on the trial site.¹⁵

Read more about AAV experimental therapies

Clinical Trials That Are Not Yet Recruiting Participants

There are also 2 new clinical trials for AAV therapies that are not yet recruiting participants. 

SATELITE 

SATELITE (NCT04871191) is a phase 2 study of salvage therapy for GPA patients with an inadequate response to standard of care therapy. It will test the efficacy of 3 different salvage strategies in inducing remission. These include a combination of Rituxan plus a conventional disease-modifying antirheumatic drug (methotrexate, Imuran, or CellCept® [mycophenolate mofetil]), Rituxan plus Actemra® (tocilizumab), or Rituxan plus Orencia. The trial aims to recruit 42 patients, aged 18 years and above, from March 2023 and is expected to be completed in January 2027.¹⁶

NCT05376319

This is a phase 2 study that will evaluate the safety and efficacy of Gazyva® (obinutuzumab) in treating proteinase 3 AAV. It aims to recruit 30 adult participants and will take place at Massachusetts General Hospital, the Mayo Clinic in Rochester, Minnesota, and the University of Pennsylvania. It is expected to start in March 2023 and be completed in July 2025.¹⁷

Read more about AAV therapies

Observational Studies

Observational studies aim to collect more information about the disease without an intervention. There are several observational studies on AAV currently underway.

BRAVO

BRAVO (NCT05716334) is a multicenter, observational study in 240 participants with GPA or MPA, aged 18 years and over, that aims to compare the safety and effectiveness of Rituxan biosimilars to the originator. The study is currently recruiting participants in Canada and is expected to be completed on September 15, 2025.¹⁸

V-PREG 

V-PREG (NCT02593565), or the Vasculitis Pregnancy Registry, at the University of Pennsylvania aims to explore the experiences of women with vasculitis, including GPA, MPA, and EGPA, who become pregnant. The study will use several online surveys to assess participants’ vasculitis severity, pregnancy-related experiences, and pregnancy outcomes. The estimated enrollment is 100 participants. The study started in November 2015 and is expected to be completed in December 2026.¹⁹ 

NCT00315380

This is a longitudinal study of EGPA to identify new biomarkers that could be used to monitor disease activity. An estimated 500 patients of different ages who are at various stages and have different disease durations will be recruited in the United States and Canada. Blood and urine samples will be collected every 6 months until study completion, which is estimated to be in April 2024.²⁰

NCT01241305

This is an observational 1-time DNA study for AAV and other types of vasculitis, the purpose of which is to identify genes that may increase the risk of developing vasculitis. An estimated 1000 patients, aged 7 years and above, will be recruited. In this study, 20 mL of blood will be collected for DNA extraction, and the clinical data of the patients and linked DNA specimens will be evaluated. The trial is currently recruiting participants in the United States, Canada, and Turkey and will be completed in August 2027.²¹

NCT02257866

The aim of this study is to investigate the natural history of idiopathic systemic vasculitis, including GPA, MPA, and EGPA, in children and adults. Around 4000 patients, aged 3 years and over, will undergo a medical history assessment, physical examination, and laboratory evaluation to study genes involved in vasculitis. The estimated study completion date is January 1, 2050.²²

Read more about AAV prognosis

References

1. ANCA vasculitis. UNC Kidney Center. Updated September 2018. Accessed February 28, 2023.
2. Yates M, Watts R. ANCA-associated vasculitis. Clin Med (Lond). 2017;17(1):60-64. doi:10.7861/clinmedicine.17-1-60
3. Efficacy and safety of rituximab in the treatment of good prognosis microscopic polyangiitis (RITUXGOPRO). ClinicalTrials.gov. April 19, 2019. Updated September 27, 2022. Accessed February 28, 2023.
4. Rituximab and belimumab combination therapy in PR3 vasculitis (COMBIVAS). ClinicalTrials.gov. May 30, 2019. Updated March 8, 2022. Accessed February 28, 2023. 
5. Maintenance of remission with rituximab versus azathioprine for newly-diagnosed or relapsing eosinophilic granulomatosis with polyangiitis. (MAINRITSEG). ClinicalTrials.gov. May 23, 2017. Updated December 13, 2022. Accessed February 28, 2023.
6. Abatacept for the treatment of relapsing, non-severe, granulomatosis with polyangiitis (Wegener’s). ClinicalTrials.gov. April 9, 2014. Updated February 6, 2023. Accessed February 28, 2023.
7. Efficacy and safety of benralizumab in EGPA compared to mepolizumab. (MANDARA). ClinicalTrials.gov. November 8, 2019. Updated December 13, 2022. Accessed February 28, 2023.
8. ETA and AT1 antagonism in ANCA-vasculitis (SPARVASC) (SPARVASC). ClinicalTrials.gov. November 29, 2022. Updated January 27, 2023. Accessed February 28, 2023.
9. Exploring durable remission with rituximab in antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis (ENDURRANCE-1). ClinicalTrials.gov. May 8, 2019. Updated May 20, 2022. Accessed February 28, 2023.
10. Study of mepolizumab-based regimen compared to conventional therapeutic strategy in patients with eosinophilic granulomatosis with polyangiitis (E-merge) (E-merge). ClinicalTrials.gov. September 1, 2021. Updated June 30, 2022. Accessed February 28, 2023.
11. The assessment of prednisone in remission trial – Centers of Excellence approach (TAPIR). ClinicalTrials.gov. September 11, 2013. Updated October 12, 2022. Accessed February 28, 2023.
12. Efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) (OCEAN). ClinicalTrials.gov. March 3, 2022. Updated February 2, 2023. Accessed February 28, 2023.
13. Hydroxychloroquine in ANCA vasculitis evaluation (HAVEN). ClinicalTrials.gov. March 20, 2020. Updated March 18, 2022. Accessed February 28, 2023.
14. Evaluate the remission maintenance using extended administration of prednisone in systemic anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. (MAINEPSAN). ClinicalTrials.gov. September 25, 2017. Updated November 22, 2019. Accessed February 28, 2023.
15. Comparison of the efficacy of leflunomide and azathioprine for the maintenance therapy of ANCA associated vasculitis (LEFAZAREM). ClinicalTrials.gov. February 3, 2021. Updated November 30, 2021. Accessed February 28, 2023.
16. Study of salvage therapy to treat patients with granulomatosis with polyangiitis (SATELITE). ClinicalTrials.gov. May 4, 2021. Updated February 8, 2023. Accessed February 28, 2023.
17. PR3-AAV resilient remission or PRRR. ClinicalTrials.gov. May 17, 2022. Updated January 3, 2023. Accessed February 28, 2023.
18. Biosimilars of rituximab in ANCA-associated vasculitis compared to the originator (BRAVO). ClinicalTrials.gov. February 8, 2023. Accessed February 28, 2023.
19. Vasculitis Pregnancy Registry (V-PREG). ClinicalTrials.gov. November 1, 2015. Updated May 18, 2022. Accessed February 28, 2023.
20. Longitudinal study for eosinophilic granulomatosis with polyangiitis (Churg-Strauss). ClinicalTrials.gov. April 18, 2006. Updated May 17, 2022. Accessed February 28, 2023.
21. One-time DNA study for vasculitis. ClinicalTrials.gov. November 16, 2010. Updated May 17, 2022. Accessed February 28, 2023.
22. Studies of the natural history, pathogenesis, and outcome of idiopathic systemic vasculitis. ClinicalTrials.gov. October 7, 2014. Updated February 8, 2023. Accessed February 28, 2023.

Reviewed by Kyle Habet, MD, on 2/28/2023.

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Ozge Ozkaya, MSc, PhD

Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.