Avacopan for Vasculitis

Recruiting at 42 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

Trial Summary

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 If you are taking azathioprine, mycophenolate, or methotrexate, these must be withdrawn before starting cyclophosphamide or rituximab.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 data supports the effectiveness of the drug Avacopan for vasculitis?

Avacopan has been approved in the USA and Japan for treating severe ANCA-associated vasculitis, showing effectiveness when used with standard therapy. A case study also showed that a patient with severe vasculitis and kidney failure improved with Avacopan after not responding to other treatments. ^{1 2 3 4 5}

Is Avacopan safe for humans?

Avacopan has been studied for safety in patients with ANCA-associated vasculitis, and it is generally considered safe when used as directed. It has been approved in several countries, including Japan and the USA, for this condition, indicating that its safety profile has been evaluated and deemed acceptable by regulatory authorities. ^{1 3 4 6 7}

How is the drug Avacopan different from other treatments for vasculitis?

Avacopan is unique because it is an oral medication that specifically blocks the C5a receptor, which plays a role in the inflammation process of vasculitis, without affecting other parts of the immune system. Unlike traditional treatments that rely heavily on glucocorticoids (steroids), Avacopan can reduce the need for these steroids, potentially minimizing their side effects. ^{1 3 4 5 6}

What is the purpose of this trial?

The primary objective of this study is to evaluate the long-term safety of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Avacopan: First Approval. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Renal improvement and remission in a patient with refractory ANCA-associated vasculitis treated with avacopan. [2023]

3. England pubmed.ncbi.nlm.nih.gov

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

Avacopan as an additional therapeutic intervention to promote renal recovery in severe ANCA-associated vasculitis: A case report. [2023]

6. Canada 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. [2020]

7. England 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. [2023]