Avacopan for Vasculitis

Recruiting at 23 trial locations

Overseen By Amgen Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Lupus, Rheumatoid vasculitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 52 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objective of this study is to explore the efficacy of avacopan in participants affected by AAV.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who need ongoing immunosuppressive treatments, including corticosteroids. This might mean you need to stop such medications to participate.

What data supports the effectiveness of the drug Avacopan for vasculitis?

Avacopan has been approved in Japan and the USA 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, even after other treatments failed. ^{1 2 3 4 5}

Is avacopan safe for humans?

Avacopan has been studied for safety in treating ANCA-associated vasculitis, and it has been approved in Japan and the USA for this condition. It is generally considered safe when used with standard therapy, but like any medication, it may have side effects. ^{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 ANCA-associated vasculitis. 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}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for children and teens aged 6 to <18 with AAV, a type of vasculitis. They must be newly diagnosed or relapsed, weigh over 15 kg, have certain levels of kidney function (eGFR > 15), and test positive for specific antibodies. Participants need to meet criteria for GPA or MPA diseases and show significant disease activity.

Inclusion Criteria

I have AAV and tested positive for anti-PR3 or anti-MPO antibodies.

I am between 6 and 17 years old.

I weigh more than 15 kilograms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avacopan twice-daily (BID) administered as oral tablets or liquid formula for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Avacopan

Trial Overview The study tests the effectiveness of Avacopan when combined with Rituximab or Cyclophosphamide in treating AAV in young patients. It aims to see if this combination can help manage symptoms better than current treatments.

Participant Groups

Group I: Avacopan Experimental Treatment 1 Intervention

Participants will receive avacopan twice-daily (BID) administered as oral tablets or liquid formula for 52 weeks.

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]