ClinicalTrials.gov record NCT07098936

Momelotinib in VEXAS Syndrome

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

A Single-arm Phase II With safety-run-in Multicenter Study of Momelotinib in Patients With VEXAS Syndrome With or Without Associated Myelodysplastic Syndrome

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age18 years old and older
SexAll
LocationFrance
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is a single-arm phase II study with a safety run-in that evaluates momelotinib in adults with VEXAS syndrome, with or without associated myelodysplastic syndrome (MDS). The study first uses a small dose-finding phase (3+3 design) to set a maximum tolerated dose, then treats a larger group at that dose and follows clinical and laboratory responses. Participants receive momelotinib continuously until disease progression, loss of response, or unacceptable side effects; steroid therapy at baseline (≥10 mg/day prednisolone equivalent) is part of the protocol. Response is assessed at several time points up to 48 weeks.

What it is studying. Whether momelotinib can be given safely and what clinical and laboratory responses occur in people with VEXAS syndrome (and associated MDS), including defining a maximum tolerated dose and measuring overall clinical response at 24 weeks.

What the researchers hope to learn. Determine the maximum tolerated dose of momelotinib; collect safety and side-effect data; measure clinical response rates for VEXAS-related inflammation and hematological responses for associated MDS; assess pharmacokinetics in the safety run-in; track steroid dose changes, overall survival, duration of response, and changes in UBA1 variant allelic frequency.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Multicenter, phase II trial with safety run-in to evaluate the efficacy and safety of momelotinib in patients with VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome with or without associated myelodysplastic syndrome (MDS). The study will consist of two consecutive steps, a dose-finding safety run-in and a single-arm prospective phase II. During safety run-in phase, three fixed dose levels will be tested according to a 3+3 design, using cohorts of size 3 in order to establish the maximum tolerated dose. After this safety run-in phase, patients included in phase II will be treated with momelotinib at the maximum tolerated dose preliminary fixed. Patients included in the phase II will receive momelotinib continuously until disease progression or loss of response, at physician's discretion. All patients included in the study will receive glucocorticoids (prednisone/prednisolone equivalent) at baseline (at least > 10mg/day). Response assessment regarding VEXAS related symptoms will be evaluated after 4, 12, 24 and 48 weeks. Response assessment regarding MDS features will be evaluated at 12 and 24 weeks.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Momelotinib treatment

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • ECOG (Eastern Cooperative Oncology Group) performance status 0-2 at the time of screening
  • Age ≥ 18 years
  • Written informed consent
  • Diagnosis of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome with UBA1 (Ubiquitin Like Modifier Activating Enzyme 1) mutation and clinically symptomatic disease requiring immunosuppressive treatment and at least 10mg/d of glucocorticoids
  • Patients 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/immunomodulatory therapy than glucocorticoids, a wash out period of 28 days is required prior momelotinib onset
  • Erythropoietin/luspatercept used as a growth factor treatment is not allowed 28 days prior enrollment
  • Adequate liver function (serum transaminases ≤ 3 x ULN (Upper Limits of Normal), Bilirubin ≤ 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin fractionated and direct bilirubin < 35%)
  • Adequate renal function (creatinine clearance with MDRD (Modification of Diet in Renal Disease) formula > 30 ml/min)
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must:
  • Have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment on this study. Lactating patients are excluded.
  • 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.
  • Agree to learn about the procedures for preservation of egg before starting treatment.
  • Male patients must:
  • 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.
  • Agree to learn about the procedures for preservation of sperm before starting treatment.

Exclusion criteria

  • Patients with MDS (Myelodysplastic syndrome) scheduled for allogeneic stem cell transplant or high risk MDS according to IWG (International Working Group) 2023
  • Patients who are or have been already treated with Janus Kinase (JAK) inhibitors for VEXAS syndrome or another indication
  • Patients who are unable to receive a starting daily dose of momelotinib of at least 100 mg
  • 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
  • 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 momelotinib
  • Known infection with acute and chronic active Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  • 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
  • Previous history of Progressive Multifocal Leuko-encephalopathy
  • Active gastrointestinal conditions that may affect absorption
  • No affiliation to a health insurance system
  • Known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

During safety run-in phase, the three fixed dose levels tested are :

  • Dose level (DL) -1: 150 mg once daily (QD)
  • DL1: 200 mg QD
  • DL2: 300 mg QD. Between 6 and 18 patients will be enrolled during the safety run-in phase. Up to 39 patients could be included in the phase II study and will be treated with momelotinib at the maximum tolerated dose preliminary fixed during the safety run-in phase.

Baseline steroids daily dose required for VEXAS inflammatory manifestations will be defined during screening period (28 days period) for each patient. It is defined as the minimal daily dose of steroids used in the last 14 days prior momelotinib onset (according to physician disposition) that allow disease control. In case of related VEXAS inflammatory manifestation during screening period with a first fixed dose, an increased dose of steroids should be evaluated during at least an extra 14 days prior momelotinib onset. This baseline dose defined during screening period will be used for response criteria during follow-up. Momelotinib treatment will be discontinued after 24 weeks at optimal dosing regimen (up to 300 mg/day), in case of absence of response. Treatment might also be discontinued during follow-up in case of loss of response/hematological progression or non-tolerable adverse event.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants receive daily momelotinib in a two-step plan: a safety run-in (small cohorts to find the tolerated dose) followed by a single-arm phase II at the selected dose, with treatment continued until progression, loss of response, or unacceptable side effects. Visits include regular clinical assessments and blood tests; VEXAS symptom response is assessed at weeks 4, 12, 24 and 48, and MDS-related assessments at weeks 12 and 24. Patients in the safety run-in will have intensive pharmacokinetic blood sampling at specified time points; steroid dose is recorded and used in response criteria. Treatment may be stopped after 24 weeks for lack of response or earlier for toxicity or disease progression.

How the study is structured. Interventional, open-label, single-group study. A safety run-in uses a 3+3 dose-escalation to find the maximum tolerated dose; after that, a phase II single arm treats patients at that dose. No masking (everyone and the investigators know the treatment). Treatment is continuous until progression, loss of response, or unacceptable toxicity. Clinical and blood-based response checks are scheduled at several weeks during the first year.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in France. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on VEXAS syndrome

Clinical trials11 trials listed for VEXAS syndromeEvery trial the registry lists for VEXAS syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in VEXAS syndrome researchLatest monthly update: September 2026. Includes: IL-6 and JAK drugs. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Nov 25, 2025
Primary completion
June 2028 (estimated)
Study completion
November 2028 (estimated)
Target enrollment
57 participants (estimated)
Last updated on registry
Aug 10, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Groupe Francophone des Myelodysplasies
Collaborators
  • GlaxoSmithKline

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (11)

Terms used on this page · explanations by MedicalUpdates.ai

run-in
A period at the start of a study, before the study treatment begins, used for example to confirm that participants meet the criteria or to record their usual symptoms.
dose-finding
Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
single-arm
All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
maximum tolerated dose
The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
glucocorticoids
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
baseline
Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
ECOG
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
Written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
immunosuppressive
A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
prior treatment
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
refractory
A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
x ULN
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
study drug
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
allogeneic stem cell transplant
A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
during screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
adverse event
Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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