PAXIS: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Study (Part 1) Followed by an Open-Label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome

TL;DR

This study is the first clinical trial to test pacritinib, a drug targeting inflammation, in patients with VEXAS syndrome, a rare and severe disease.

Contribution

The PAXIS trial introduces a novel, prospective, randomized study design for VEXAS syndrome, a condition with no prior pharmacotherapeutic trials.

Findings

Pacritinib is being evaluated as a potential GC-sparing therapy for VEXAS syndrome.

The trial uses disease-specific endpoints to assess efficacy and safety of pacritinib.

This is the first randomized pharmacotherapeutic study in VEXAS syndrome patients.

Abstract

VEXAS (Vacuoles, E1 ubiquitin-activating enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a systemic disorder characterized by an overlap of hematologic and inflammatory features. Most patients require chronic use of moderate-to-high doses of glucocorticoids (GCs) to maintain disease control. Data on GC-sparing therapies is limited, and there have been no prospective pharmacotherapeutic trials in VEXAS syndrome published to date. Pacritinib, an oral inhibitor of IRAK1, JAK2, and ACVR1, has emerged as a promising therapeutic option for VEXAS syndrome. The PAXIS trial is the first prospective, randomized pharmacotherapeutic study conducted in this rare and severe disease. Utilizing a novel study design and disease-specific endpoints, the trial will evaluate the efficacy and safety of two dose levels of pacritinib compared with placebo in patients with VEXAS syndrome (NCT06782373, EUCTR: 2024-516347-41-00).

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