Amgen has launched a Phase 3 clinical trial to investigate the efficacy and safety of Tavneos (avacopan) in pediatric patients with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), the most common forms of ANCA-associated vasculitis (AAV). The study, identified as NCT06321601, is enrolling children and adolescents aged 6 to 17. This initiative follows the existing approval of Tavneos for treating adults with severe and active GPA or MPA.
Trial Design and Objectives
The open-label Phase 3 trial intends to enroll up to 20 participants across sites in Indiana, North Carolina, and Ohio. Eligible patients include those newly diagnosed or experiencing a relapse of GPA or MPA, with a weight exceeding 15 kilograms. Participants will receive Tavneos twice daily, administered orally as tablets or a liquid formulation, in conjunction with a standard regimen of rituximab or cyclophosphamide, for a duration of 52 weeks.
The primary endpoint of the study is to determine the proportion of patients achieving disease remission after 26 weeks of treatment, as assessed by the Pediatric Vasculitis Activity Score. A secondary goal is to evaluate the percentage of patients with sustained remission at 52 weeks. Additional secondary endpoints encompass safety measures, disease remission rates based on the Birmingham Vasculitis Activity Score, changes in the Physician Global Assessment of disease activity, and the Pediatric Vasculitis Damage Index.
Tavneos Mechanism and Prior Clinical Data
Tavneos is an orally administered small molecule that selectively binds to the C5a receptor, thereby blocking its interaction with C5a. By inhibiting this interaction, Tavneos is expected to reduce the recruitment of immune cells, alleviate inflammation, and prevent damage to small blood vessels in AAV. The drug's approval for adults was supported by data from the Phase 3 ADVOCATE trial (NCT02994927), which demonstrated the superiority of Tavneos over high-dose glucocorticoids in 330 patients undergoing immunosuppressive treatment with either cyclophosphamide followed by azathioprine or rituximab. The ADVOCATE trial showed that a higher proportion of patients achieved remission after one year with Tavneos, along with improvements in kidney function and reduced reliance on glucocorticoids.
ANCA-Associated Vasculitis and Unmet Needs
AAV is an autoimmune disease characterized by inflammation and damage to small blood vessels, predominantly affecting the kidneys and lungs. Most cases involve self-reactive antibodies (ANCAs) targeting proteinase 3 (PR3) and myeloperoxidase (MPO) in neutrophils. The activation of the complement system, particularly the generation of C5a, contributes to the damaging effects of ANCAs by recruiting immune cells and inflammatory signals to small blood vessels.
The current standard treatment for AAV includes glucocorticoids and immunosuppressants like rituximab and cyclophosphamide. While effective, long-term glucocorticoid use is associated with significant side effects, highlighting the need for steroid-sparing therapies like Tavneos. This pediatric trial aims to address the unmet need for effective and safer treatments for children with AAV.
Additional Assessments
Beyond clinical assessments, the trial will also analyze changes in blood levels of Tavneos, biomarkers of kidney function, and glucocorticoid dosage. Participants will also evaluate the taste of the pediatric liquid formulation using the TASTY faces scale. The study is anticipated to conclude around mid-2030.
