Momelotinib in VEXAS syndrome

Trial details

Who runs it

Groupe Francophone Des Myelodysplasies

Trial code

EU 2024-519779-24-00

Record updated

2026. október 19.

Original description

Safety run-in :To determine the maximum tolerated dose (MTD) of momelotinib (MMB) in VEXAS patients Phase II : To determine clinical efficacy of MMB at 24 weeks on VEXAS related symptoms in UBA1 mutated and symptomatic patients refractory/dependent to steroidsRead full original descriptionShow less

GFM-VEXAS-MMB: A single-arm phase II with safety run-in multicenter study of momelotinib in patients with VEXAS syndrome with or without associated myelodysplastic syndrome

Safety run-in :To determine the maximum tolerated dose (MTD) of momelotinib (MMB) in VEXAS patients Phase II : To determine clinical efficacy of MMB at 24 weeks on VEXAS related symptoms in UBA1 mutated and symptomatic patients refractory/dependent to steroids

Inclusion: ECOG performance status 0-2 at the time of screening; Adequate liver function (serum transaminases ≤ 3N, Bilirubin ≤ 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%)); Adequate renal function (creatinine clearance with MDRD formula > 30 ml/min); Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must: 1- Have a negative serum or urine pregnancy test within 24-hours prior to beginning treatment on this study. Lactating patients are excluded. 2- Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 12 weeks after the end of the study drug therapy. 3- Agree to learn about the procedures for preservation of egg before starting treatment; Male patients must: 1- Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 12 weeks after end of treatment. 2- Agree to learn about the procedures for preservation of sperm before starting treatment; Age ≥ 18 years; Written informed consent; Diagnosis of VEXAS syndrome with UBA1 mutation and clinically symptomatic disease requiring corticosteroid therapy with more than 10 mg/day of prednisone equivalent; With uncontrolled symptoms related to VEXAS with prior treatment line(s) (including steroids); Patients refractory/dependent to steroids; Single concomitant steroids therapy (e.g. prednisone or equivalent) at the time of inclusion is allowed; For patients treated with other immunosuppressive/immuno-modulatory therapy than glucocorticoids, a wash out period of 28 days is required prior MMB onset; Erythropoietin/luspatercept used as a growth factor is not allowed 28 days prior enrollment.

Exclusion: Patients with MDS currently scheduled for allogeneic stem cell transplant or high risk MDS according to IWG 2023; Patients who are or have been already treated with JAK inhibitors for VEXAS syndrome or another indication; Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 12 weeks prior to initiation of MMB; Previous history of Progressive Multifocal Leuko-encephalopathy (PML); Active gastrointestinal conditions that may affect absorption; Known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients; Subjects with any other active malignancies are not eligible, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which subject has been disease-free for at least 3 years; Known infection with acute and chronic active HIV, HBV, HCV infections; Any medical or psychiatric condition not allowing the informed consent of the subject; Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy; No affiliation to a health insurance system; Patients who are unable to receive a starting daily dose of MMB of at least 100 mg.

EU CTIS 2024-519779-24-00