Phase 3 trial of Tavneos enrolling children, ages 6-17, with AAV
Eligible patients are newly diagnosed, or relapsed, with active GPA or MPA
A new Phase 3 clinical trial is recruiting children and adolescents with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), the most common types of ANCA-associated vasculitis (AAV), to test Tavneos (avacopan) in combination with rituximab or cyclophosphamide.
That’s according to a financial update released by Amgen, the developer of Tavneos, which is approved for treating adults with severe and active GPA or MPA.
The pediatric study (NCT06321601), whose plans were shared by the company earlier this year, is expected to enroll up to 20 patients, ages 6-17, at sites in Indiana, North Carolina, and Ohio. Eligible participants are those with either newly diagnosed disease or relapsed disease, and weighing over 15 kilograms (about 33 pounds).
Tavneos is approved for adults with severe and active GPA or MPA
An autoimmune disease, AAV is marked by inflammation and damage to small blood vessels that most commonly affect the kidneys and lungs. Most cases are associated with the generation of self-reactive antibodies, called ANCAs, that primarily target one of two enzymes — proteinase 3 (PR3) and myeloperoxidase (MPO) — in a type of immune cell called neutrophils.
ANCAs’ damaging effects are partly driven by neutrophil-induced activation of the complement system, a group of immune proteins that normally help fight potential threats.
Such activation generates a complement protein called C5a, which binds to receptors on immune cells and cells that line blood vessels. This results in the accumulation of immune cells and inflammatory signals near small blood vessels, causing damage.
Tavneos is an orally available small molecule that selectively binds to the C5a receptor, blocking its interaction with C5a. In this way, the treatment is expected to reduce the number of recruited immune cells, ease inflammation, and prevent damage to small blood vessels in AAV.
It’s approved in several countries, including the U.S., as an add-on to standard AAV treatment for adults with severe and active GPA or MPA.
Data from the Phase 3 ADVOCATE trial (NCT02994927), which tested the therapy against standard high-dose glucocorticoids in 330 patients on immunosuppressive treatment with either cyclophosphamide followed by azathioprine or with rituximab, supported Tavneos’ approvals.
After one year, the proportion of patients who achieved remission was higher among those given Tavneos. The therapy also improved kidney function and reduced the reliance on glucocorticoids, which are associated with harmful side effects when taken long term.
Children in the Phase 3 trial will be treated with Tavneos twice daily
Amgen has now launched an open-label Phase 3 trial to assess Tavneos’ effectiveness, pharmacological properties, and safety in pediatric GPA and MPA patients. Participants must test positive for ANCAs against PR3 or MPO and have functioning kidneys.
All enrolled will be given Tavneos twice daily as oral tablets or a liquid formulation, in combination with a standard regimen containing rituximab or cyclophosphamide, for 52 weeks (about one year).
As a primary goal, the study will assess the proportion of patients who achieve disease remission, as determined using the Pediatric Vasculitis Activity Score, after 26 weeks (about six months) of treatment. The percentage of those with sustained remission will be assessed at 52 weeks.
Secondary goals include safety measures and additional efficacy measures, such as the proportion of patients achieving disease remission as assessed by the Birmingham Vasculitis Activity Score, and changes in the Physician Global Assessment of disease activity and the Pediatric Vasculitis Damage Index.
Other secondary measures will analyze changes in blood levels of Tavneos and biomarkers of kidney function, as well as changes in glucocorticoid dosage. Participants also will be asked to complete the TASTY faces scale, assessing the perceived taste of the pediatric liquid formula.
The study is expected to end around mid-2030.
About the Author
