Avacopan for Vasculitis

Recruiting at 33 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called avacopan (Tavneos) for vasculitis, an autoimmune disease. The goal is to evaluate avacopan's effectiveness in children and teens with specific forms of this condition, such as granulomatosis with polyangiitis or microscopic polyangiitis. Participants should have tested positive for certain antibodies related to their condition and show symptoms like protein or blood in their urine. The trial seeks young individuals who have been newly diagnosed or have experienced a flare-up. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that avacopan is likely to be safe for humans?

Research has shown that avacopan is generally safe for people. In earlier studies, serious infections occurred in 3.6% of those taking avacopan, compared to 6.7% of those not taking it. This suggests avacopan might pose a lower risk of causing serious infections than other treatments. Additionally, 34.6% of people on avacopan reported serious side effects, slightly less than the 39.3% of people on a different treatment.

Avacopan is already approved for treating ANCA-associated vasculitis (AAV), indicating it has been proven safe enough for that use. Overall, evidence suggests that most people tolerate avacopan well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for vasculitis, like corticosteroids and immunosuppressants, focus on broadly dampening the immune system. But Avacopan works differently by specifically targeting a protein called C5a receptor within the immune system. This helps to reduce inflammation more precisely, potentially minimizing the side effects associated with standard treatments. Researchers are excited because Avacopan is administered orally, which could offer a more convenient option compared to intravenous therapies.

What evidence suggests that avacopan might be an effective treatment for vasculitis?

Research has shown that avacopan, which participants in this trial will receive, can effectively treat ANCA-associated vasculitis (AAV). One study found that 71.7% of patients achieved remission by week 26. Another study demonstrated that avacopan helped maintain remission for up to 52 weeks and reduced the risk of recurrence. These findings suggest that avacopan can help manage AAV by controlling the disease and preventing flare-ups. ^{1 3 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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, 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 (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]

Citations

1. 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 ...

2. 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.

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 ...