ATLAS: A Randomized, Double-Blind, Placebo-Controlled, Adaptive Seamless Phase 2/3 Study to Assess the Safety and Efficacy of Momelotinib in Patients With VEXAS Syndrome
Materials and Methods/Case Presentation/Objective:
DESIGN: ATLAS is a multicenter, double-blind, seamless phase 2/3 study designed to prospectively assess the efficacy, safety, and pharmacokinetics of momelotinib in VEXAS. The trial is expected to enroll ≈150 patients. Phase 2 will randomize patients, stratified by baseline GC dose, 1:1:1 to receive 1 of 2 doses of momelotinib or placebo for 26 weeks. A protocol-defined GC taper during the blinded treatment regimen is required; GC rescue therapy for flares is permitted. For phase 3, if futility for momelotinib is not declared at the interim analysis, additional patients will be enrolled and randomized 1:1 to receive momelotinib recommended phase 3 dose (RP3D) or placebo; all patients enrolled in phase 2 who have not met disease progression will remain blinded until phase 3 patients finish 26 weeks of treatment.
Eligible patients have a UBA1 mutation, inflammatory manifestations, and ongoing GC treatment. Exclusion criteria include platelet counts < 50×109/L or absolute neutrophil counts < 1×109/L, history of severe corticosteroid toxicity, and high-/very-high-risk myelodysplastic syndromes. Patients with >1 prior line of VEXAS-directed therapy before or after VEXAS diagnosis or other medical condition will be excluded.
METHODS: The primary endpoint will be overall response rate (complete/partial response based on absence of flares and reduction of GC daily dose) at week 26. Secondary endpoints will include RP3D identification (phase 2), safety, patient-reported outcomes, hematologic improvement, pharmacokinetics, and overall survival. Exploratory endpoints will include transfusion rates, GC dose changes, and clonal burden.
Results/Description/Main Outcome Measure(s):
STATUS: As of June 2026, enrollment for ATLAS has commenced, with an estimated primary completion date of December 2028.
This abstract was accepted and previously presented at the European Alliance of Associations for Rheumatology (EULAR) congress. All rights reserved.
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