Last updated: 04/28/2026 16:40:09
A Study Evaluating the Efficacy and Safety of Momelotinib in Participants with Vacuoles, E1-enzyme, X-linked, autoinflammatory, somatic (VEXAS) SyndromeATLAS
GSK study ID
223401
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Trial status
Not yet recruiting
Not yet recruiting
Trial overview
Official title: A Randomized Phase 2/3, Double-blind, Placebo Controlled Adaptive Study Evaluating the Efficacy and Safety of Momelotinib in Participants with VEXAS Syndrome
Trial description: This study will assess the efficacy and safety of momelotinib in participants with a diagnosis of VEXAS.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
ORR (Objective response rate) at Week 26
Timeframe: At Week 26
Secondary outcomes:
Phase 2: Percentage of participants with partial response (PR) or complete response (CR) at Week 26
Timeframe: At Week 26
Phase 2: Number of participants with adverse events and clinically significant changes in laboratory parameters, and vital signs to support identification of the RP3D
Timeframe: Up to 26 Weeks
Phase 2: Plasma concentrations of momelotinib and metabolite of momelotinib 21 (M21) to support identification of the RP3D
Timeframe: Up to 26 Weeks
Number of flare-free days
Timeframe: Up to 26 Weeks
Duration of response (DoR)
Timeframe: Up to 104 Weeks
Number of flare-free days with glucocorticoid (GC) dose <=10 mg/day
Timeframe: Up to 104 Weeks
Percentage of participants achieving complete and partial biochemical response
Timeframe: Up to 26 Weeks
Objective response rate (ORR) at Week 52
Timeframe: At Week 52
Number of Participants with Hematologic Improvement- Erythroid (HI-E) response per International Working Group (IWG) 2018 criteria
Timeframe: Up to 26 Weeks
Change from Baseline in Short Form 36 (SF-36) domain and summary scores
Timeframe: Baseline and up to Week 48
Change from Baseline in European Organization for Research and Treatment of Cancer Item Library (EORTC IL) 479 score
Timeframe: Baseline and up to Week 156
Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Physical Function Short Form 10b
Timeframe: Baseline and up to Week 156
Change from Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-FATIGUE)
Timeframe: Baseline and up to Week 156
Changes from Baseline in Patient Global Impression of Severity (PGIS) scores
Timeframe: Baseline and up to Week 156
Changes in Patient Global Impression of Change (PGIC) scores
Timeframe: Baseline and up to Week 156
Changes from Baseline in European quality of life 5 dimensions 5 level version (EQ-5D-5L)
Timeframe: Baseline and up to Week 48
Changes from Baseline in European quality of life-Visual Analogue Scale (EQ-VAS)
Timeframe: Baseline and up to Week 48
Number of participants with adverse events (AEs) and Serious adverse events (SAEs)
Timeframe: Up to Week 108
Number of participants with adverse events (AEs) and Serious adverse events (SAEs) by severity
Timeframe: Up to Week 108
Number of participants with AEs leading to discontinuation or dose modifications
Timeframe: Up to Week 108
Plasma concentration of momelotinib and M21
Timeframe: Up to 26 Weeks
Overall Survival
Timeframe: At Months 12, 24 and 36
Interventions:
Enrollment:
192
Observational study model:
Not applicable
Primary completion date:
2028-06-12
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
VEXAS syndrome
Product
Not applicable
Collaborators
Not applicable
Study date(s)
August 2026 to June 2031
Type
Interventional
Phase
2/3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Age greater than equal to (>=)18 years OR of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the Informed Consent Form.
- Confirmed diagnosis of clinical VEXAS defined by:
- More than 1 prior admission to an intensive care unit due to a VEXAS flare within the 6 months prior to randomization.
- History of severe corticosteroid toxicity: uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, nausea or vomiting or gastrointestinal disease.
Inclusion and exclusion criteria
Inclusion criteria:
- Age greater than equal to (>=)18 years OR of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the Informed Consent Form.
- Confirmed diagnosis of clinical VEXAS defined by: a. Documented evidence of a canonical, pathogenic Ubiquitin-like modifier activating enzyme 1 (UBA1) mutation b. Inflammatory manifestations: current or documented past involvement within 6 months of at least one organ system
- Receiving glucocorticoid (GC) treatment (prednisone/prednisolone) for >=4 consecutive weeks for >=10 days prior to randomization.
- A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: a. Is a Participant of non-childbearing potential (PONCBP) OR b. Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective
- Is capable of giving signed informed consent including compliance with the requirements and restrictions
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at the time of screening.
- Has adequate organ function
Exclusion criteria:
- More than 1 prior admission to an intensive care unit due to a VEXAS flare within the 6 months prior to randomization.
- History of severe corticosteroid toxicity: uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, nausea or vomiting or gastrointestinal disease.
- High risk/very high risk Myelodysplastic syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-R) with overall risk score >3.5.
- Peripheral blood blast counts >=10%.
- Multiple myeloma (all stages) and other active plasma cell dyscrasias requiring treatment.
- Malignancy (except disease under study including Lower-risk myelodysplastic syndrome [LR-MDS]) that has progressed or required active treatment within the past (24 months) except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas).
- Uncontrolled intercurrent illness within 12 weeks prior to initiation of momelotinib.
- Ongoing adverse reaction(s) from prior therapy that have not recovered to Grade <=1 per NCI CTCAE v6.0 or to the Baseline status preceding prior therapy
- Psychiatric illness, social situation, or any other condition that would limit informed consent and/or compliance with trial requirements or may interfere with the interpretation of study results, as judged by Investigator or Sponsor.
- Has any clinically significant gastrointestinal conditions or abnormalities that may alter absorption or swallowing
- Known contraindication or hypersensitivity to momelotinib and its metabolites, or any of their excipients.
- Presence of peripheral neuropathy >=Grade 2 per NCI CTCAE v6.0.
- Known history of disseminated mycobacterial infection.
- Known positive status for human immunodeficiency virus (HIV).
- Positive QuantiFERON (or other interferon gamma release assay) during Screening.
- Unable to receive any Pneumocystis jiroveci pneumonia (PJP) medical prophylaxis
- Known clinically significant anemia due to iron, vitamin B12 or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
- More than 1 prior line of VEXAS directed therapy before or after VEXAS diagnosis or other medical condition.
- Use of the following treatments within the noted time periods referenced from date of randomization: a. VEXAS-directed therapies (washout period) up to 5 half-lives or up 14 days if half-life is <3 days b. Other non-GC anti-inflammatory therapies: for non-biologics): 14 days or five half-lives, whichever is longer; for biologics): 28 days or two half-lives whichever is longer. c. Hematologic support therapy (e.g., ESAs, danazol, luspatercept, G-CSF): 4 weeks d. Cell-depleting therapies such as anti-CD20 (rituximab): 12 months e. Investigational agent from a class not otherwise specified: 5 half-lives or 60 days, whichever is longer
- GC use for conditions other than VEXAS, which would interfere with adherence to the fixed GC taper regimen and/or to assessment of efficacy.
- Chronic use of systemic corticosteroids for >4 years or inability to withdraw corticosteroid treatment
- Planned allogeneic HSCT for MDS or VEXAS, within 1 year.
- Any major surgery within 28 days prior to randomization.
- Prior allogeneic/autologous stem cell transplant or solid organ transplant (other than corneal).
- Presence of peripheral neuropathy >=Grade 2 per NCI CTCAE v6.0.
- Hepatitis B or C active infection, unless protocol defined criteria are met.
- Any of the following conditions within 6 months prior to randomization: a. Unstable angina pectoris b. Symptomatic congestive heart failure c. Uncontrolled cardiac arrhythmia d. QTc >450 msec or QTc >480 msec for participants with bundle branch block.
Trial location(s)
No location data available.
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Not yet recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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