Avacopan for Vasculitis

Recruiting at 75 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Amgen

Must be taking: Cyclophosphamide, Rituximab

Must not be taking: Corticosteroids, Antitumor necrosis factor

Disqualifiers: Autoimmune diseases, Hepatitis, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called avacopan (Tavneos) to determine its safety for long-term use in individuals with ANCA-associated vasculitis, a specific type of blood vessel inflammation. The trial compares avacopan to a placebo, both used alongside standard treatments. It suits those recently diagnosed or experiencing a relapse of conditions such as granulomatosis with polyangiitis or microscopic polyangiitis, who require treatments like cyclophosphamide or rituximab. Participants should exhibit specific symptoms, such as blood in urine or positive antibody tests. As a Phase 4 trial, avacopan has already received FDA approval and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped before participation. If you are taking azathioprine, mycophenolate, or methotrexate, these must be withdrawn before starting cyclophosphamide or rituximab. Additionally, if you are on a strong or moderate inducer of the CYP3A4 enzyme, it must be changed to an alternative at least 1 week before starting the trial.

What is the safety track record for Avacopan?

Studies have shown that avacopan is generally well-tolerated by people with ANCA-associated vasculitis. Research indicates that avacopan causes fewer serious side effects compared to traditional treatments. For example, those taking avacopan report fewer serious infections than those not taking it. Other evidence shows that avacopan is linked with fewer serious adverse events overall compared to other treatments.

Additionally, avacopan is approved for use in adults with ANCA-associated vasculitis, indicating it has met strict safety standards for this condition. However, like any treatment, it can have side effects, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Avacopan for treating vasculitis because it offers a new way to manage the condition. Unlike traditional treatments that rely heavily on corticosteroids, Avacopan specifically targets the C5a receptor, a part of the immune system involved in inflammation. This targeted approach has the potential to reduce the side effects associated with long-term steroid use. Additionally, Avacopan is taken orally, making it more convenient compared to some other treatments that require injections. Overall, Avacopan could provide a more precise and patient-friendly option for managing vasculitis.

What is the effectiveness track record for Avacopan in treating vasculitis?

Research has shown that avacopan works well for treating ANCA-associated vasculitis (AAV). One study found that 71.7% of patients achieved remission at 26 weeks compared to those taking prednisone. Another study demonstrated that avacopan helped maintain remission for up to 52 weeks and reduced the risk of disease recurrence. These findings support avacopan's effectiveness in managing AAV. In this trial, participants may receive avacopan alongside standard care, avacopan for one year followed by a placebo, or a placebo with standard care. The treatment's approval underscores its proven success for this condition. ^{1 4 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a new or returning diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, needing cyclophosphamide or rituximab treatment. They must have tested positive for ANCA antibodies and show significant symptoms of vasculitis. Participants need at least minimal kidney function to join.

Inclusion Criteria

At least 1 Birmingham Vasculitis Activity Score (BVAS) major item, at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria

I have a new or returning diagnosis of GPA or MPA and need specific treatment.

eGFR 15 mL/min/1.73 m^2 (using Chronic Kidney Disease Epidemiology Collaboration equations)

Exclusion Criteria

Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) before signing of the informed consent

Positive test for active or latent tuberculosis during screening

Aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >2.0 times the upper limit of normal (ULN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avacopan or placebo with standard of care for up to 5 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Avacopan

Trial Overview The study aims to assess the long-term safety of avacopan in treating ANCA-associated vasculitis. It involves comparing avacopan against a placebo, alongside standard treatments like cyclophosphamide or rituximab, which are already used for this condition.

How Is the Trial Designed?

Group I: Group B: Avacopan/Placebo + SoC Experimental Treatment 3 Interventions

Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.

Group II: Group A: Avacopan + Standard of Care (SoC) Experimental Treatment 2 Interventions

Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.

Group III: Group C: Placebo + SoC Placebo Group 2 Interventions

Placebo twice daily for 5 years + SoC background immunosuppressive therapy.

Avacopan is already approved in United States for the following indications:

Approved in United States as Tavneos for:

• ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis)

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Avacopan (TAVNEOS™) is a complement 5a receptor antagonist approved in Japan and the USA for treating ANCA-associated vasculitis, specifically microscopic polyangiitis and granulomatosis with polyangiitis, highlighting its efficacy in managing these autoimmune diseases.

While avacopan is effective as an adjunctive treatment, it does not replace glucocorticoids, indicating that it works alongside standard therapies to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avacopan: First Approval. Lee, A.[2022]

Avacopan demonstrated a remission rate of 65.7% in patients with ANCA-associated vasculitis, significantly higher than the 54.9% remission rate observed in the placebo group during the 52-week ADVOCATE trial.

In the CLEAR trial, avacopan-treated patients showed a greater improvement in the Birmingham Vasculitis Activity Score (≥50% improvement in 86.4% of patients) compared to those treated with prednisone, suggesting avacopan may offer similar or better efficacy with potentially fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Alihosseini, C., Kopelman, H., Zaino, M., et al.[2023]

Avacopan, a selective C5a receptor antagonist, has been approved as an adjunctive treatment for severe ANCA-associated vasculitis, showing promise in improving patient outcomes when combined with standard therapies like glucocorticoids.

In a case study of a 58-year-old woman with severe ANCA-associated vasculitis who was resistant to previous treatments (rituximab and glucocorticoids), avacopan led to a positive response, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal improvement and remission in a patient with refractory ANCA-associated vasculitis treated with avacopan. Alvarez, L., Kambham, N., Su, R.[2023]

Avacopan is a novel oral medication designed to selectively block the C5a receptor, potentially replacing glucocorticoids in treating ANCA-associated vasculitis, which is a serious autoimmune disease.

The study aims to evaluate the efficacy and safety of avacopan compared to prednisone in 300 patients, with the primary goal of achieving remission without the use of glucocorticoids by week 26 and sustained remission by week 52.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial. Merkel, PA., Jayne, DR., Wang, C., et al.[2020]

Avacopan, a C5a receptor antagonist, offers a promising new treatment option for patients with ANCA-associated vasculitis (AAV), which can lead to severe kidney issues.

In a case report, avacopan was successfully added to the treatment regimen of a patient who initially required kidney replacement therapy, suggesting its potential effectiveness even in advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avacopan as an additional therapeutic intervention to promote renal recovery in severe ANCA-associated vasculitis: A case report. Atrens, AD., Hutton, H., O'Sullivan, E., et al.[2023]

In a subgroup analysis of the Phase 3 ADVOCATE study, avacopan demonstrated a high clinical remission rate of 81.8% at Week 26 in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis, compared to 70.0% for tapered prednisone.

Avacopan also showed a higher sustained remission rate at Week 52 (72.7%) compared to prednisone (40.0%), indicating its potential as an effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of avacopan in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: A subanalysis of a randomized Phase 3 study. Harigai, M., Kaname, S., Tamura, N., et al.[2023]

The Canadian Vasculitis Research Network has updated its recommendations for using avacopan in treating ANCA-associated vasculitides (AAV), based on a systematic review of evidence up to September 2022.

Three new recommendations were established regarding the indication and duration of avacopan therapy, as well as the importance of tapering glucocorticoids in a timely manner, providing clear guidance for healthcare professionals managing AAV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum. Turgeon, D., Bakowsky, V., Baldwin, C., et al.[2023]

Citations

1. tavneospro.com tavneospro.com/results/efficacy

Efficacy | TAVNEOS® (avacopan) Find the efficacy data on TAVNEOS® as an oral adjunctive therapy in the ADVOCATE trial. See full prescribing & safety info.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40037556/?utm_source=Feedly

Efficacy and safety of avacopan in patients aged 65 years and ... Remission at week 26 was achieved in 71.7% vs 69.4% of patients aged 65-74 and 73.1% vs 72.0% aged ≥75 in the avacopan vs prednisone taper ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39352795/

The real-world use and effectiveness of avacopan in ... Results: Twenty-nine patients treated with avacopan were analysed. Twelve patients (41.4%) were male, and median age was 56 years. Most patients ...

4. ard.bmj.com ard.bmj.com/content/83/2/223

Efficacy and safety of avacopan in patients with ANCA ... These data confirm and add to the current evidence of the role of avacopan as a therapeutic agent to sustain remission to 52 weeks and reduce the risk of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925003456

Treatment With Avacopan in ANCA–Associated Vasculitis ... Key efficacy outcomes were remission at week 26, sustained remission at week 52, and relapse after remission through week 52. Changes in estimated glomerular ...

6. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.70001

Safety of Avacopan for the Treatment of Antineutrophil ... Six patients (3.6%) in the avacopan group and 11 (6.7%) in the non-avacopan group had serious opportunistic infections. No infections caused by ...

7. journals.lww.com journals.lww.com/jasn/fulltext/2022/11001/integrated_safety_of_avacopan_in_anca_associated.2824.aspx

Integrated Safety of Avacopan in ANCA-Associated Vasculitis Avacopan (TAVNEOS®) is approved as adjunctive treatment for adults with ANCA-associated vasculitis (AAV). Integrated safety data from 2 Phase 2 and 1 Phase 3 ...

8. healio.com healio.com/news/rheumatology/20250709/avacopan-yields-strong-safety-profile-in-ancaassociated-vasculitis

Avacopan yields strong safety profile in ANCA-associated ... Avacopan was associated with fewer serious adverse events than controls in ANCA-associated vasculitis. · Data from three trials showed improved ...